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Chapter 1 Exploring Life

Chapter Notes

Overview: Biology’s Most Exciting Era

 Biology is the scientific study of life.

 You are starting your study of biology during its most exciting era.
 The largest and best-equipped community of scientists in history is beginning to solve
problems that once seemed unsolvable.
 Biology is an ongoing inquiry about the nature of life.
 Biologists are moving closer to understanding:
 How a single cell develops into an adult animal or plant.
 How plants convert solar energy into the chemical energy of food.
 How the human mind works.
 How living things interact in biological communities.
 How the diversity of life evolved from the first microbes.
 Research breakthroughs in genetics and cell biology are transforming medicine and
 Neuroscience and evolutionary biology are reshaping psychology and sociology.
 Molecular biology is providing new tools for anthropology and criminology.
 New models in ecology are helping society to evaluate environmental issues, such as
the causes and biological consequences of global warming.
 Unifying themes pervade all of biology.

Concept 1.1 Biologists explore life from the microscopic to the global scale
 Life’s basic characteristic is a high degree of order.
 Each level of biological organization has emergent properties.
 Biological organization is based on a hierarchy of structural levels, each building on the
levels below.
 At the lowest level are atoms that are ordered into complex biological molecules.
 Biological molecules are organized into structures called organelles, the components of
 Cells are the fundamental unit of structure and function of living things.
 Some organisms consist of a single cell; others are multicellular aggregates of specialized
 Whether multicellular or unicellular, all organisms must accomplish the same functions:
uptake and processing of nutrients, excretion of wastes, response to environmental
stimuli, and reproduction.
 Multicellular organisms exhibit three major structural levels above the cell: similar
cells are grouped into tissues, several tissues coordinate to form organs, and several
organs form an organ system.
Biology Chapter Notes
 For example, to coordinate locomotory movements, sensory information travels from
sense organs to the brain, where nervous tissues composed of billions of interconnected
neurons—supported by connective tissue—coordinate signals that travel via other neurons
to the individual muscle cells.
 Organisms belong to populations, localized groups of organisms belonging to the same
 Populations of several species in the same area comprise a biological community.
 Populations interact with their physical environment to form an ecosystem.
 The biosphere consists of all the environments on Earth that are inhabited by life.
Organisms interact continuously with their environment.
 Each organism interacts with its environment, which includes other organisms as well as
nonliving factors.
 Both organism and environment are affected by the interactions between them.
 The dynamics of any ecosystem include two major processes: the cycling of nutrients and
the flow of energy from sunlight to producers to consumers.
 In most ecosystems, producers are plants and other photosynthetic organisms that
convert light energy to chemical energy.
 Consumers are organisms that feed on producers and other consumers.
 All the activities of life require organisms to perform work, and work requires a source of
 The exchange of energy between an organism and its environment often involves the
transformation of energy from one form to another.
 In all energy transformations, some energy is lost to the surroundings as heat.
 In contrast to chemical nutrients, which recycle within an ecosystem, energy flows
through an ecosystem, usually entering as light and exiting as heat.
Cells are an organism’s basic unit of structure and function.
 The cell is the lowest level of structure that is capable of performing all the activities of
 For example, the ability of cells to divide is the basis of all reproduction and the basis
of growth and repair of multicellular organisms.
 Understanding how cells work is a major research focus of modern biology.
 At some point, all cells contain deoxyribonucleic acid, or DNA, the heritable material that
directs the cell’s activities.
 DNA is the substance of genes, the units of inheritance that transmit information from
parents to offspring.
 Each of us began life as a single cell stocked with DNA inherited from our parents.
 DNA in human cells is organized into chromosomes.
 Each chromosome has one very long DNA molecule, with hundreds or thousands of
genes arranged along its length.
 The DNA of chromosomes replicates as a cell prepares to divide.
 Each of the two cellular offspring inherits a complete set of genes.
 In each cell, the genes along the length of DNA molecules encode the information for
building the cell’s other molecules.
 DNA thus directs the development and maintenance of the entire organism.
Biology Chapter Notes
 Most genes program the cell’s production of proteins.
 Each DNA molecule is made up of two long chains arranged in a double helix.
 Each link of a chain is one of four nucleotides, encoding the cell’s information in
chemical letters.
 The sequence of nucleotides along each gene codes for a specific protein with a unique
shape and function.
 Almost all cellular activities involve the action of one or more proteins.
 DNA provides the heritable blueprints, but proteins are the tools that actually build and
maintain the cell.
 All forms of life employ essentially the same genetic code.
 Because the genetic code is universal, it is possible to engineer cells to produce
proteins normally found only in some other organism.
 The library of genetic instructions that an organism inherits is called its genome.
 The chromosomes of each human cell contain about 3 billion nucleotides, including
genes coding for more than 70,000 kinds of proteins, each with a specific function.
 Every cell is enclosed by a membrane that regulates the passage of material between a cell
and its surroundings.
 Every cell uses DNA as its genetic material.
 There are two basic types of cells: prokaryotic cells and eukaryotic cells.
 The cells of the microorganisms called bacteria and archaea are prokaryotic.
 All other forms of life have more complex eukaryotic cells.
 Eukaryotic cells are subdivided by internal membranes into various organelles.
 In most eukaryotic cells, the largest organelle is the nucleus, which contains the cell’s
DNA as chromosomes.
 The other organelles are located in the cytoplasm, the entire region between the
nucleus and outer membrane of the cell.
 Prokaryotic cells are much simpler and smaller than eukaryotic cells.
 In a prokaryotic cell, DNA is not separated from the cytoplasm in a nucleus.
 There are no membrane-enclosed organelles in the cytoplasm.
 All cells, regardless of size, shape, or structural complexity, are highly ordered structures
that carry out complicated processes necessary for life.

Concept 1.2 Biological systems are much more than the sum of their parts
 “The whole is greater than the sum of its parts.”
 The combination of components can form a more complex organization called a system.
 Examples of biological systems are cells, organisms, and ecosystems.
 Consider the levels of life.
 With each step upward in the hierarchy of biological order, novel properties emerge
that are not present at lower levels.
 These emergent properties result from the arrangements and interactions between
components as complexity increases.
 A cell is much more than a bag of molecules.
Biology Chapter Notes
 Our thoughts and memories are emergent properties of a complex network of neurons.
 This theme of emergent properties accents the importance of structural arrangement.
 The emergent properties of life are not supernatural or unique to life but simply reflect a
hierarchy of structural organization.
 The emergent properties of life are particularly challenging because of the unparalleled
complexity of living systems.
 The complex organization of life presents a dilemma to scientists seeking to understand
biological processes.
 We cannot fully explain a higher level of organization by breaking it down into its
component parts.
 At the same time, it is futile to try to analyze something as complex as an organism or
cell without taking it apart.
 Reductionism, reducing complex systems to simpler components, is a powerful strategy in
 The Human Genome Project—the sequencing of the genome of humans and many
other species—is heralded as one of the greatest scientific achievements ever.
 Research is now moving on to investigate the function of genes and the coordination of
the activity of gene products.
 Biologists are beginning to complement reductionism with new strategies for
understanding the emergent properties of life—how all of the parts of biological systems
are functionally integrated.
 The ultimate goal of systems biology is to model the dynamic behavior of whole
biological systems.
 Accurate models allow biologists to predict how a change in one or more variables will
impact other components and the whole system.
 Scientists investigating ecosystems pioneered this approach in the 1960s with elaborate
models diagramming the interactions of species and nonliving components in ecosystems.
 Systems biology is now becoming increasingly important in cellular and molecular
biology, driven in part by the deluge of data from the sequencing of genomes and our
increased understanding of protein functions.
 In 2003, a large research team published a network of protein interactions within a cell
of a fruit fly.
 Three key research developments have led to the increased importance of systems
1. High-throughput technology. Systems biology depends on methods that can
analyze biological materials very quickly and produce enormous amounts of data.
An example is the automatic DNA-sequencing machines used by the Human
Genome Project.
2. Bioinformatics. The huge databases from high-throughput methods require
computing power, software, and mathematical models to process and integrate
3. Interdisciplinary research teams. Systems biology teams may include engineers,
medical scientists, physicists, chemists, mathematicians, and computer scientists as
well as biologists.
Regulatory mechanisms ensure a dynamic balance in living systems.

Biology Chapter Notes

 Chemical processes within cells are accelerated, or catalyzed, by specialized protein
molecules, called enzymes.
 Each type of enzyme catalyzes a specific chemical reaction.
 In many cases, reactions are linked into chemical pathways, each step with its own
 How does a cell coordinate its various chemical pathways?
 Many biological processes are self-regulating: the output or product of a process
regulates that very process.
 In negative feedback, or feedback inhibition, accumulation of an end product of a
process slows or stops that process.
 Though less common, some biological processes are regulated by positive feedback, in
which an end product speeds up its own production.
 Feedback is common to life at all levels, from the molecular level to the biosphere.
 Such regulation is an example of the integration that makes living systems much greater
than the sum of their parts.

Concept 1.3 Biologists explore life across its great diversity of species
 Biology can be viewed as having two dimensions: a “vertical” dimension covering the
size scale from atoms to the biosphere and a “horizontal” dimension that stretches across
the diversity of life.
 The latter includes not only present-day organisms, but also those that have existed
throughout life’s history.
Living things show diversity and unity.
 Life is enormously diverse.
 Biologists have identified and named about 1.8 million species.
 This diversity includes 5,200 known species of prokaryotes, 100,000 fungi, 290,000
plants, 50,000 vertebrates, and 1,000,000 insects.
 Thousands of newly identified species are added each year.
 Estimates of the total species count range from 10 million to more than 200 million.
 In the face of this complexity, humans are inclined to categorize diverse items into a
smaller number of groups.
 Taxonomy is the branch of biology that names and classifies species into a hierarchical
 Until the past decade, biologists divided the diversity of life into five kingdoms.
 New methods, including comparisons of DNA among organisms, have led to a
reassessment of the number and boundaries of the kingdoms.
 Various classification schemes now include six, eight, or even dozens of kingdoms.
 Coming from this debate has been the recognition that there are three even higher levels
of classifications, the domains.
 The three domains are Bacteria, Archaea, and Eukarya.
 The first two domains, domain Bacteria and domain Archaea, consist of prokaryotes.
 All the eukaryotes are now grouped into various kingdoms of the domain Eukarya.
Biology Chapter Notes
 The recent taxonomic trend has been to split the single-celled eukaryotes and their
close relatives into several kingdoms.
 Domain Eukarya also includes the three kingdoms of multicellular eukaryotes: the
kingdoms Plantae, Fungi, and Animalia.
 These kingdoms are distinguished partly by their modes of nutrition.
 Most plants produce their own sugars and food by photosynthesis.
 Most fungi are decomposers that absorb nutrients by breaking down dead organisms
and organic wastes.
 Animals obtain food by ingesting other organisms.
 Underlying the diversity of life is a striking unity, especially at the lower levels of
 The universal genetic language of DNA unites prokaryotes and eukaryotes.
 Among eukaryotes, unity is evident in many details of cell structure.
 Above the cellular level, organisms are variously adapted to their ways of life.
 How do we account for life’s dual nature of unity and diversity?
 The process of evolution explains both the similarities and differences among living

Concept 1.4 Evolution accounts for life’s unity and diversity

 The history of life is a saga of a changing Earth billions of years old, inhabited by a
changing cast of living forms.
 Charles Darwin brought evolution into focus in 1859 when he presented two main
concepts in one of the most important and controversial books ever written, On the Origin
of Species by Natural Selection.
 Darwin’s first point was that contemporary species arose from a succession of ancestors
through “descent with modification.”
 This term captured the duality of life’s unity and diversity: unity in the kinship among
species that descended from common ancestors and diversity in the modifications that
evolved as species branched from their common ancestors.
 Darwin’s second point was his mechanism for descent with modification: natural
 Darwin inferred natural selection by connecting two observations:
 Observation 1: Individual variation. Individuals in a population of any species vary in
many heritable traits.
 Observation 2: Overpopulation and competition. Any population can potentially
produce far more offspring than the environment can support. This creates a struggle
for existence among variant members of a population.
 Inference: Unequal reproductive success. Darwin inferred that those individuals with
traits best suited to the local environment would leave more healthy, fertile offspring.
 Inference: Evolutionary adaptation. Unequal reproductive success can lead to
adaptation of a population to its environment. Over generations, heritable traits that
enhance survival and reproductive success will tend to increase in frequency among a
population’s individuals. The population evolves.
 Natural selection, by its cumulative effects over vast spans of time, can produce new
species from ancestral species.
Biology Chapter Notes
 For example, a population fragmented into several isolated populations in different
environments may gradually diversify into many species as each population adapts
over many generations to different environmental problems.
 Fourteen species of finches found on the Galápagos Islands diversified after an ancestral
finch species reached the archipelago from the South American mainland.
 Each species is adapted to exploit different food sources on different islands.
 Biologists’ diagrams of evolutionary relationships generally take a treelike form.
 Just as individuals have a family tree, each species is one twig of a branching tree of life.
 Similar species like the Galápagos finches share a recent common ancestor.
 Finches share a more distant ancestor with all other birds.
 The common ancestor of all vertebrates is even more ancient.
 Trace life back far enough, and there is a shared ancestor of all living things.
 All of life is connected through its long evolutionary history.

Concept 1.5 Biologists use various forms of inquiry to explore life

 The word science is derived from a Latin verb meaning “to know.”
 At the heart of science is inquiry, people asking questions about nature and focusing on
specific questions that can be answered.
 The process of science blends two types of exploration: discovery science and hypothesis-
based science.
 Discovery science is mostly about discovering nature.
 Hypothesis-based science is mostly about explaining nature.
 Most scientific inquiry combines the two approaches.
 Discovery science describes natural structures and processes as accurately as possible
through careful observation and analysis of data.
 Discovery science built our understanding of cell structure and is expanding our
databases of genomes of diverse species.
 Observation is the use of the senses to gather information, which is recorded as data.
 Data can be qualitative or quantitative.
 Quantitative data are numerical measurements.
 Qualitative data may be in the form of recorded descriptions.
 Jane Goodall has spent decades recording her observations of chimpanzee behavior
during field research in Gambia.
 She has also collected volumes of quantitative data over that time.
 Discovery science can lead to important conclusions based on inductive reasoning.
 Through induction, we derive generalizations based on a large number of specific
 In science, inquiry frequently involves the proposing and testing of hypotheses.
 A hypothesis is a tentative answer to a well-framed question.
 It is usually an educated postulate, based on past experience and the available data of
discovery science.

Biology Chapter Notes

 A scientific hypothesis makes predictions that can be tested by recording additional
observations or by designing experiments.
 A type of logic called deduction is built into hypothesis-based science.
 In deductive reasoning, reasoning flows from the general to the specific.
 From general premises, we extrapolate to a specific result that we should expect if the
premises are true.
 In hypothesis-based science, deduction usually takes the form of predictions about what
we should expect if a particular hypothesis is correct.
 We test the hypothesis by performing the experiment to see whether or not the results
are as predicted.
 Deductive logic takes the form of “If . . . then” logic.
 Scientific hypotheses must be testable.
 There must be some way to check the validity of the idea.
 Scientific hypotheses must be falsifiable.
 There must be some observation or experiment that could reveal if a hypothesis is
actually not true.
 The ideal in hypothesis-based science is to frame two or more alternative hypotheses and
design experiments to falsify them.
 No amount of experimental testing can prove a hypothesis.
 A hypothesis gains support by surviving various tests that could falsify it, while testing
falsifies alternative hypotheses.
 Facts, in the form of verifiable observations and repeatable experimental results, are the
prerequisites of science.
We can explore the scientific method.
 There is an idealized process of inquiry called the scientific method.
 Very few scientific inquiries adhere rigidly to the sequence of steps prescribed by the
textbook scientific method.
 Discovery science has contributed a great deal to our understanding of nature without
most of the steps of the so-called scientific method.
 We will consider a case study of scientific research.
 This case begins with a set of observations and generalizations from discovery science.
 Many poisonous animals have warning coloration that signals danger to potential
 Imposter species mimic poisonous species, although they are harmless.
 An example is the bee fly, a nonstinging insect that mimics a honeybee.
 What is the function of such mimicry? What advantage does it give the mimic?
 In 1862, Henry Bates proposed that mimics benefit when predators mistake them for
harmful species.
 This deception may lower the mimic’s risk of predation.
 In 2001, David and Karin Pfennig and William Harcombe of the University of North
Carolina designed a set of field experiments to test Bates’s mimicry hypothesis.
 In North and South Carolina, a poisonous snake called the eastern coral snake has warning
red, yellow, and black coloration.
Biology Chapter Notes
 Predators avoid these snakes. It is unlikely that predators learn to avoid coral snakes, as a
strike is usually lethal.
 Natural selection may have favored an instinctive recognition and avoidance of the
warning coloration of the coral snake.
 The nonpoisonous scarlet king snake mimics the ringed coloration of the coral snake.
 Both king snakes and coral snake live in the Carolinas, but the king snake’s range also
extends into areas without coral snakes.
 The distribution of these two species allowed the Pfennigs and Harcombe to test a key
prediction of the mimicry hypothesis.
 Mimicry should protect the king snake from predators, but only in regions where coral
snakes live.
 Predators in non–coral snake areas should attack king snakes more frequently than
predators that live in areas where coral snakes are present.
 To test the mimicry hypothesis, Harcombe made hundreds of artificial snakes.
 The experimental group had the red, black, and yellow ring pattern of king snakes.
 The control group had plain, brown coloring.
 Equal numbers of both types were placed at field sites, including areas where coral snakes
are absent.
 After four weeks, the scientists retrieved the fake snakes and counted bite or claw marks.
 Foxes, coyotes, raccoons, and black bears attacked snake models.
 The data fit the predictions of the mimicry hypothesis.
 The ringed snakes were attacked by predators less frequently than the brown snakes
only within the geographic range of the coral snakes.
 The snake mimicry experiment provides an example of how scientists design experiments
to test the effect of one variable by canceling out the effects of unwanted variables.
 The design is called a controlled experiment.
 An experimental group (artificial king snakes) is compared with a control group
(artificial brown snakes).
 The experimental and control groups differ only in the one factor the experiment is
designed to test—the effect of the snake’s coloration on the behavior of predators.
 The brown artificial snakes allowed the scientists to rule out such variables as predator
density and temperature as possible determinants of number of predator attacks.
 Scientists do not control the experimental environment by keeping all variables constant.
 Researchers usually “control” unwanted variables, not by eliminating them but by
canceling their effects using control groups.
Let’s look at the nature of science.
 There are limitations to the kinds of questions that science can address.
 These limits are set by science’s requirements that hypotheses are testable and falsifiable
and that observations and experimental results be repeatable.
 The limitations of science are set by its naturalism.
 Science seeks natural causes for natural phenomena.
 Science cannot support or falsify supernatural explanations, which are outside the
bounds of science.
 Everyday use of the term theory implies an untested speculation.
Biology Chapter Notes
 The term theory has a very different meaning in science.
 A scientific theory is much broader in scope than a hypothesis.
 This is a hypothesis: “Mimicking poisonous snakes is an adaptation that protects
nonpoisonous snakes from predators.”
 This is a theory: “Evolutionary adaptations evolve by natural selection.”
 A theory is general enough to generate many new, specific hypotheses that can be tested.
 Compared to any one hypothesis, a theory is generally supported by a much more massive
body of evidence.
 The theories that become widely adopted in science (such as the theory of adaptation by
natural selection) explain many observations and are supported by a great deal of
 In spite of the body of evidence supporting a widely accepted theory, scientists may have
to modify or reject theories when new evidence is found.
 As an example, the five-kingdom theory of biological diversity eroded as new
molecular methods made it possible to test some of the hypotheses about the
relationships between living organisms.
 Scientists may construct models in the form of diagrams, graphs, computer programs, or
mathematical equations.
 Models may range from lifelike representations to symbolic schematics.
 Science is an intensely social activity.
 Most scientists work in teams, which often include graduate and undergraduate
 Both cooperation and competition characterize scientific culture.
 Scientists attempt to confirm each other’s observations and may repeat experiments.
 They share information through publications, seminars, meetings, and personal
 Scientists may be very competitive when converging on the same research question.
 Science as a whole is embedded in the culture of its times.
 For example, recent increases in the proportion of women in biology have had an
impact on the research being performed.
 For instance, there has been a switch in focus in studies of the mating behavior of animals
from competition among males for access to females to the role that females play in
choosing mates.
 Recent research has revealed that females prefer bright coloration that “advertises” a
male’s vigorous health, a behavior that enhances a female’s probability of having
healthy offspring.
 Some philosophers of science argue that scientists are so influenced by cultural and
political values that science is no more objective than other ways of “knowing nature.”
 At the other extreme are those who view scientific theories as though they were natural
 The reality of science is somewhere in between.
 The cultural milieu affects scientific fashion, but need for repeatability in observation and
hypothesis testing distinguishes science from other fields.
 If there is “truth” in science, it is based on a preponderance of the available evidence.

Biology Chapter Notes

Science and technology are functions of society.
 Although science and technology may employ similar inquiry patterns, their basic goals
 The goal of science is to understand natural phenomena.
 Technology applies scientific knowledge for some specific purpose.
 Technology results from scientific discoveries applied to the development of goods and
 Scientists put new technology to work in their research.
 Science and technology are interdependent.
 The discovery of the structure of DNA by Watson and Crick sparked an explosion of
scientific activity.
 These discoveries made it possible to manipulate DNA, enabling genetic technologists
to transplant foreign genes into microorganisms and mass-produce valuable products.
 DNA technology and biotechnology have revolutionized the pharmaceutical industry.
 They have had an important impact on agriculture and the legal profession.
 The direction that technology takes depends less on science than it does on the needs of
humans and the values of society.
 Debates about technology center more on “should we do it” than “can we do it.”
 With advances in technology come difficult choices, informed as much by politics,
economics, and cultural values as by science.
 Scientists should educate politicians, bureaucrats, corporate leaders, and voters about how
science works and about the potential benefits and hazards of specific technologies.

Concept 1.6 A set of themes connects the concepts of biology

 In some ways, biology is the most demanding of all sciences, partly because living
systems are so complex and partly because biology is a multidisciplinary science that
requires knowledge of chemistry, physics, and mathematics.
 Biology is also the science most connected to the humanities and social sciences.

Biology Chapter Notes

Chapter 2 The Chemical Context of Life
Chapter Notes

Overview: Chemical Foundations of Biology

 Living organisms and the world they live in are subject to the basic laws of physics and
 Biology is a multidisciplinary science, drawing on insights from other sciences.
 Life can be organized into a hierarchy of structural levels.
 At each successive level, additional emergent properties appear.

Concept 2.1 Matter consists of chemical elements in pure form and in combinations
called compounds
 Organisms are composed of matter.
 Matter is anything that takes up space and has mass.
 Matter is made up of elements.
 An element is a substance that cannot be broken down into other substances by chemical
 There are 92 naturally occurring elements.
 Each element has a unique symbol, usually the first one or two letters of the name.
Some of the symbols are derived from Latin or German names.
 A compound is a substance consisting of two or more elements in a fixed ratio.
 Table salt (sodium chloride or NaCl) is a compound with equal numbers of atoms of
the elements chlorine and sodium.
 While pure sodium is a metal and chlorine is a gas, they combine to form an edible
compound. This change in characteristics when elements combine to form a compound
is an example of an emergent property.
25 chemical elements are essential to life.
 About 25 of the 92 natural elements are known to be essential for life.
 Four elements—carbon (C), oxygen (O), hydrogen (H), and nitrogen (N)—make up
96% of living matter.
 Most of the remaining 4% of an organism’s weight consists of phosphorus (P), sulfur
(S), calcium (Ca), and potassium (K).
 Trace elements are required by an organism but only in minute quantities.
 Some trace elements, like iron (Fe), are required by all organisms.
 Other trace elements are required by only some species.
 For example, a daily intake of 0.15 milligrams of iodine is required for normal
activity of the human thyroid gland.

Concept 2.2 An element’s properties depend on the structure of its atoms

 Each element consists of unique atoms.
Biology Chapter Notes
 An atom is the smallest unit of matter that still retains the properties of an element.
 Atoms are composed of even smaller parts, called subatomic particles.
 Two of these, neutrons and protons, are packed together to form a dense core, the
atomic nucleus, at the center of an atom.
 Electrons can be visualized as forming a cloud of negative charge around the nucleus.
 Each electron has one unit of negative charge.
 Each proton has one unit of positive charge.
 Neutrons are electrically neutral.
 The attractions between the positive charges in the nucleus and the negative charges of the
electrons keep the electrons in the vicinity of the nucleus.
 A neutron and a proton are almost identical in mass, about 1.7 × 10 −24 gram per particle.
 For convenience, a smaller unit of measure, the dalton, is used to measure the mass of
subatomic particles, atoms, or molecules.
 The mass of a neutron or a proton is close to 1 dalton.
 The mass of an electron is about 1/2000 that of a neutron or proton.
 Therefore, we typically ignore the contribution of electrons when determining the total
mass of an atom.
 All atoms of a particular element have the same number of protons in their nuclei.
 This number of protons is the element’s unique atomic number.
 The atomic number is written as a subscript before the symbol for the element. For
example, 2He means that an atom of helium has 2 protons in its nucleus.
 Unless otherwise indicated, atoms have equal numbers of protons and electrons and,
therefore, no net charge.
 Therefore, the atomic number tells us the number of protons and the number of
electrons that are found in a neutral atom of a specific element.
 The mass number is the sum of the number of protons and neutrons in the nucleus of an
 Therefore, we can determine the number of neutrons in an atom by subtracting the
number of protons (the atomic number) from the mass number.
 The
mass number is written as a superscript before an element’s symbol (for example,
 The atomic weight of an atom, a measure of its mass, can be approximated by the mass
 For example, 4He has a mass number of 4 and an estimated atomic weight of 4 daltons.
More precisely, its atomic weight is 4.003 daltons.
 While all atoms of a given element have the same number of protons, they may differ in
the number of neutrons.
 Two atoms of the same element that differ in the number of neutrons are called isotopes.
 In nature, an element occurs as a mixture of isotopes.
 For example, 99% of carbon atoms have 6 neutrons (12C).
 Most of the remaining 1% of carbon 14
atoms have 7 neutrons ( 13C) while the rarest
carbon isotope, with 8 neutrons, is C.
 Most isotopes are stable; they do not tend to lose particles.
 Both 12C and 13C are stable isotopes.
Biology Chapter Notes
 The nuclei of some isotopes are unstable and decay spontaneously, emitting particles and
 14C is one of these unstable isotopes, or radioactive isotopes.
 When 14C decays, one of its neutrons is converted to a proton and an electron.
 This converts 14C to 14N, transforming the atom to a different element.
 Radioactive isotopes have many applications in biological research.
 Radioactive decay rates can be used to date fossils.
 Radioactive isotopes can be used to trace atoms through metabolic processes.
 Radioactive isotopes are also used to diagnose medical disorders.
 For example, a known quantity of a substance labeled with a radioactive isotope can be
injected into the blood, and its rate of excretion in the urine can be measured.
 Also, radioactive tracers can be used with imaging instruments to monitor chemical
processes in the body.
 While useful in research and medicine, the energy emitted in radioactive decay is
hazardous to life.
 This energy can destroy molecules within living cells.
 The severity of damage depends on the type and amount of radiation that the organism
Electron configuration influences the chemical behavior of an atom.
 Simplified models of the atom greatly distort the atom’s relative dimensions.
 To gain an accurate perspective of the relative proportions of an atom, if the nucleus was
the size of a golf ball, the electrons would be moving about 1 kilometer from the nucleus.
 Atoms are mostly empty space.
 When two elements interact during a chemical reaction, it is actually their electrons that
are involved.
 The nuclei do not come close enough to interact.
 The electrons of an atom vary in the amount of energy they possess.
 Energy is the ability to do work.
 Potential energy is the energy that matter stores because of its position or location.
 Water stored behind a dam has potential energy that can be used to do work turning
electric generators.
 Because potential energy has been expended, the water stores less energy at the bottom
of the dam than it did in the reservoir.
 Electrons have potential energy because of their position relative to the nucleus.
 The negatively charged electrons are attracted to the positively charged nucleus.
 The farther electrons are from the nucleus, the more potential energy they have.
 Changes in an electron’s potential energy can only occur in steps of a fixed amount,
moving the electron to a fixed location relative to the nucleus.
 An electron cannot exist between these fixed locations.
 The different states of potential energy that the electrons of an atom can have are called
energy levels or electron shells.
 The first shell, closest to the nucleus, has the lowest potential energy.
 Electrons in outer shells have more potential energy.
Biology Chapter Notes
 Electrons can change their position only if they absorb or release a quantity of energy
that matches the difference in potential energy between the two levels.
 The chemical behavior of an atom is determined by its electron configuration—the
distribution of electrons in its electron shells.
 The first 18 elements, including those most important in biological processes, can be
arranged in 8 columns and 3 rows.
 Elements in the same row fill the same shells with electrons.
 Moving from left to right, each element adds one electron (and proton) from the
element before.
 The first electron shell can hold only 2 electrons.
 The two electrons of helium fill the first shell.
 Atoms with more than two electrons must place the extra electrons in higher shells.
 For example, lithium, with three electrons, has two in the first shell and one in the
second shell.
 The second shell can hold up to 8 electrons.
 Neon, with 10 total electrons, has two in the first shell and eight in the second, filling
both shells.
 The chemical behavior of an atom depends mostly on the number of electrons in its
outermost shell, the valence shell.
 Electrons in the valence shell are known as valence electrons.
 Lithium has one valence electron; neon has eight.
 Atoms with the same number of valence electrons have similar chemical behaviors.
 An atom with a completed valence shell, like neon, is nonreactive.
 All other atoms are chemically reactive because they have incomplete valence shells.
 The paths of electrons are often portrayed as concentric paths, like planets orbiting the
 In reality, an electron occupies a more complex three-dimensional space, an orbital.
 The orbital represents the space in which the electron is found 90% of the time.
 Each orbital can hold a maximum of two electrons.
 The first shell has room for a single spherical 1s orbital for its pair of electrons.
 The second shell can pack pairs of electrons into a spherical 2s orbital and three
dumbbell-shaped 2p orbitals.
 The reactivity of atoms arises from the presence of unpaired electrons in one or more
orbitals of their valence shells.
 Electrons occupy separate orbitals within the valence shell until forced to share
 The four valence electrons of carbon each occupy separate orbitals, but the five
valence electrons of nitrogen are distributed into three unshared orbitals and one
shared orbital.
 When atoms interact to complete their valence shells, it is the unpaired electrons that are

Biology Chapter Notes

Concept 2.3 The formation and function of molecules depend on chemical bonding
between atoms
 Atoms with incomplete valence shells can interact with each other by sharing or
transferring valence electrons.
 These interactions typically result in the atoms remaining close together, held by
attractions called chemical bonds.
 The strongest chemical bonds are covalent bonds and ionic bonds.
 A covalent bond is formed by the sharing of a pair of valence electrons by two atoms.
 If two atoms come close enough that their unshared orbitals overlap, they will share
their newly paired electrons. Each atom can count both electrons toward its goal of
filling the valence shell.
 For example, if two hydrogen atoms come close enough that their 1s orbitals overlap,
then they can share a pair of electrons, with each atom contributing one.
 Two or more atoms held together by covalent bonds constitute a molecule.
 We can abbreviate the structure of the molecule by substituting a line for each pair of
shared electrons, drawing the structural formula.
 H—H is the structural formula for the covalent bond between two hydrogen atoms.
 The molecular formula indicates the number and types of atoms present in a single
 H2 is the molecular formula for hydrogen gas.
 Oxygen needs to add 2 electrons to the 6 already present to complete its valence shell.
 Two oxygen atoms can form a molecule by sharing two pairs of valence electrons.
 These atoms have formed a double covalent bond.
 Every atom has a characteristic total number of covalent bonds that it can form, equal to
the number of unpaired electrons in the outermost shell. This bonding capacity is called
the atom’s valence.
 The valence of hydrogen is 1.
 Oxygen is 2.
 Nitrogen is 3.
 Carbon is 4.
 Phosphorus should have a valence of 3, based on its three unpaired electrons, but in
biological molecules it generally has a valence of 5, forming three single covalent
bonds and one double bond.
 Covalent bonds can form between atoms of the same element or atoms of different
 While both types are molecules, the latter are also compounds.
 Water, H2O, is a compound in which two hydrogen atoms form single covalent bonds
with an oxygen atom.
 This satisfies the valences of both elements.
 Methane, CH4, satisfies the valences of both C and H.
 The attraction of an atom for the shared electrons of a covalent bond is called its
 Strongly electronegative atoms attempt to pull the shared electrons toward themselves.
 If electrons in a covalent bond are shared equally, then this is a nonpolar covalent bond.
 A covalent bond between two atoms of the same element is always nonpolar.
Biology Chapter Notes
 A covalent bond between atoms that have similar electronegativities is also nonpolar.
 Because carbon and hydrogen do not differ greatly in electronegativities, the bonds
of CH4 are nonpolar.
 When two atoms that differ in electronegativity bond, they do not share the electron pair
equally and form a polar covalent bond.
 The bonds between oxygen and hydrogen in water are polar covalent because oxygen
has a much higher electronegativity than does hydrogen.
 Compounds with a polar covalent bond have regions of partial negative charge near the
strongly electronegative atom and regions of partial positive charge near the weakly
electronegative atom.
 An ionic bond can form if two atoms are so unequal in their attraction for valence
electrons that one atom strips an electron completely from the other.
 For example, sodium, with one valence electron in its third shell, transfers this electron
to chlorine, with 7 valence electrons in its third shell.
 Now, sodium has a full valence shell (the second) and chlorine has a full valence shell
(the third).
 After the transfer, both atoms are no longer neutral, but have charges and are called ions.
 Sodium has one more proton than electrons and has a net positive charge.
 Atoms with positive charges are cations.
 Chlorine has one more electron than protons and has a net negative charge.
 Atoms with negative charges are anions.
 Because of differences in charge, cations and anions are attracted to each other to form an
ionic bond.
 Atoms in an ionic bond need not have acquired their charges by transferring electrons
with each other.
 Compounds formed by ionic bonds are ionic compounds, or salts. An example is NaCl,
or table salt.
 The formula for an ionic compound indicates the ratio of elements in a+ crystal −of that
salt. NaCl is not a molecule, but a salt crystal with equal numbers of Na and Cl ions.
 Ionic compounds can have ratios of elements different from 1:1.
 For example, the ionic compound magnesium chloride (MgCl 2) has 2 chloride atoms
per magnesium atom.
 Magnesium needs to lose 2 electrons to drop to a full outer shell; each chlorine
atom needs to gain 1.
 Entire molecules that have full electrical charges are also called ions.
 In the salt ammonium chloride (NH4Cl), the anion is Cl− and the cation is NH4+.
 The strength of ionic bonds depends on environmental conditions, such as moisture.
 Water can dissolve salts by reducing the attraction between the salt’s anions and cations.
Weak chemical bonds play important roles in the chemistry of life.
 Within a cell, weak, brief bonds between molecules are important to a variety of
 For example, signal molecules from one neuron use weak bonds to bind briefly to
receptor molecules on the surface of a receiving neuron.
 This triggers a response by the recipient.
Biology Chapter Notes
 Weak interactions include ionic bonds (weak in water), hydrogen bonds, and van der
Waals interactions.
 Hydrogen bonds form when a hydrogen atom already covalently bonded to a strongly
electronegative atom is attracted to another strongly electronegative atom.
 These strongly electronegative atoms are typically nitrogen or oxygen.
 These bonds form because a polar covalent bond leaves the hydrogen atom with a
partial positive charge and the other atom with a partial negative charge.
 The partially positive–charged hydrogen atom is attracted to regions of full or partial
negative charge on molecules, atoms, or even regions of the same large molecule.
 For example, ammonia molecules and water molecules interact with weak hydrogen
 In the ammonia molecule, the hydrogen atoms have partial positive charges, and the
more electronegative nitrogen atom has a partial negative charge.
 In the water molecule, the hydrogen atoms also have partial positive charges, and the
oxygen atom has a partial negative charge.
 Areas with opposite charges are attracted.
 Even molecules with nonpolar covalent bonds can have temporary regions of partial
negative and positive charge.
 Because electrons are constantly in motion, there can be periods when they accumulate
by chance in one area of a molecule.
 This creates ever-changing regions of partial negative and positive charge within a
 Molecules or atoms in close proximity can be attracted by these fleeting charge
differences, creating van der Waals interactions.
 While individual bonds (ionic, hydrogen, van der Waals) are weak and temporary,
collectively they are strong and play important biological roles.
A molecule’s biological function is related to its shape.
 The three-dimensional shape of a molecule is an important determinant of its function in a
 A molecule with two atoms is always linear.
 However, a molecule with more than two atoms has a more complex shape.
 The shape of a molecule is determined by the positions of the electron orbitals that are
shared by the atoms involved in the bond.
 When covalent bonds form, the orbitals in the valence shell of each atom rearrange.
 For atoms with electrons in both s and p orbitals, the formation of a covalent bonds leads
to hybridization of the orbitals to four new orbitals in a tetrahedral shape.
 In a water molecule, two of oxygen’s four hybrid orbitals are shared with hydrogen atoms.
The water molecule is shaped like a V, with its two covalent bonds spread apart at an
angle of 104.5°.
 In a methane molecule (CH4), the carbon atom shares all four of its hybrid orbitals with H
atoms. The carbon nucleus is at the center of the tetrahedron, with hydrogen nuclei at the
four corners.
 Large organic molecules contain many carbon atoms. In these molecules, the tetrahedral
shape of carbon bonded to four other atoms is often a repeating motif.

Biology Chapter Notes

 Biological molecules recognize and interact with one another with a specificity based on
molecular shape.
 For example, signal molecules from a transmitting cell have specific shapes that bind to
complementary receptor molecules on the surface of the receiving cell.
 The temporary attachment of the receptor and signal molecule stimulates activity in the
receptor cell.
 Molecules with similar shapes can have similar biological effects.
 For example, morphine, heroin, and other opiate drugs are similar enough in shape that
they can bind to the same receptors as natural signal molecules called endorphins.
 Binding of endorphins to receptors on brain cells produces euphoria and relieves pain.
Opiates mimic these natural endorphin effects.

Concept 2.4 Chemical reactions make and break chemical bonds

 In chemical reactions, chemical bonds are broken and reformed, leading to new
arrangements of atoms.
 The starting molecules in the process are called reactants, and the final molecules are
called products.
 In a chemical reaction, all of the atoms in the reactants must be present in the products.
 The reactions must be “balanced”.
 Matter is conserved in a chemical reaction.
 Chemical reactions rearrange matter; they do not create or destroy matter.
 For example, we can recombine the covalent bonds of H2 and O2 to form the new bonds of
 In this reaction, two molecules of H2 combine with one molecule of O2 to form two
molecules of H2O.
 Photosynthesis is an important chemical reaction.
 Humans and other animals ultimately depend on photosynthesis for food and oxygen.
 Green plants combine carbon dioxide (CO2) from the air and water (H2O) from the soil
to create sugar molecules and release molecular oxygen (O2) as a by-product.
 This chemical reaction is powered by sunlight.
 The overall process of photosynthesis is 6CO2 + 6H2O --> C6H12O6 + 6O2.
 This process occurs in a sequence of individual chemical reactions that rearrange the
atoms of the reactants to form the products.
 Some chemical reactions go to completion; that is, all the reactants are converted to
 Most chemical reactions are reversible, with the products in the forward reaction
becoming the reactants for the reverse reaction.
 For example in this reaction: 3H2 + N2 <=> 2NH3 hydrogen and nitrogen molecules
combine to form ammonia, but ammonia can decompose to hydrogen and nitrogen
 Initially, when reactant concentrations are high, they frequently collide to create
 As products accumulate, they collide to reform reactants.

Biology Chapter Notes

 Eventually, the rate of formation of products is the same as the rate of breakdown of
products (formation of reactants), and the system is at chemical equilibrium.
 At equilibrium, products and reactants are continually being formed, but there is no net
change in the concentrations of reactants and products.
 At equilibrium, the concentrations of reactants and products are typically not equal, but
their concentrations have stabilized at a particular ratio.

Biology Chapter Notes

Chapter 3 Water and the Fitness of the Environment
Chapter Notes

Overview: The Molecule That Supports All of Life

 Because water is the substance that makes life possible on Earth, astronomers hope to find
evidence of water on newly discovered planets orbiting distant stars.
 Life on Earth began in water and evolved there for 3 billion years before colonizing the
 Even terrestrial organisms are tied to water.
 Most cells are surrounded by water.
 Cells are about 70–95% water.
 Water is a reactant in many of the chemical reactions of life.
 Water is the only common substance that exists in the natural world in all three physical
states of matter: solid ice, liquid water, and water vapor.

Concept 3.1 The polarity of water molecules results in hydrogen bonding

 In a water molecule, two hydrogen atoms form single polar covalent bonds with an
oxygen atom.
 Because oxygen is more electronegative than hydrogen, the region around the oxygen
atom has a partial negative charge.
 The regions near the two hydrogen atoms have a partial positive charge.
 A water molecule is a polar molecule in which opposite ends of the molecule have
opposite charges.
 Water has a variety of unusual properties because of the attraction between polar water
 The slightly negative regions of one water molecule are attracted to the slightly
positive regions of nearby water molecules, forming hydrogen bonds.
 Each water molecule can form hydrogen bonds with up to four neighbors.

Concept 3.2 Four emergent properties of water contribute to Earth’s fitness for life
Organisms depend on the cohesion of water molecules.
 The hydrogen bonds joining water molecules are weak, about 1/20 as strong as covalent
 They form, break, and reform with great frequency. Each hydrogen bond lasts only a few
trillionths of a second.
 At any instant, a substantial percentage of all water molecules are bonded to their
neighbors, creating a high level of structure.
 Collectively, hydrogen bonds hold water together, a phenomenon called cohesion.
 Cohesion among water molecules plays a key role in the transport of water and dissolved
nutrients against gravity in plants.
Biology Chapter Notes
 Water molecules move from the roots to the leaves of a plant through water-
conducting vessels.
 As water molecules evaporate from a leaf, other water molecules from vessels in the
leaf replace them.
 Hydrogen bonds cause water molecules leaving the vessels to tug on molecules farther
 This upward pull is transmitted down to the roots.
 Adhesion, clinging of one substance to another, contributes too, as water adheres to
the wall of the vessels.
 Surface tension, a measure of the force necessary to stretch or break the surface of a
liquid, is related to cohesion.
 Water has a greater surface tension than most other liquids because hydrogen bonds
among surface water molecules resist stretching or breaking the surface.
 Water behaves as if covered by an invisible film.
 Some animals can stand, walk, or run on water without breaking the surface.
Water moderates temperatures on Earth.
 Water stabilizes air temperatures by absorbing heat from warmer air and releasing heat to
cooler air.
 Water can absorb or release relatively large amounts of heat with only a slight change in
its own temperature.
 Atoms and molecules have kinetic energy, the energy of motion, because they are always
 The faster a molecule moves, the more kinetic energy it has.
 Heat is a measure of the total quantity of kinetic energy due to molecular motion in a
body of matter.
 Temperature measures the intensity of heat in a body of matter due to the average
kinetic energy of molecules.
 As the average speed of molecules increases, a thermometer will record an increase in
 Heat and temperature are related, but not identical.
 When two objects of different temperatures come together, heat passes from the warmer
object to the cooler object until the two are the same temperature.
 Molecules in the cooler object speed up at the expense of kinetic energy of the warmer
 Ice cubes cool a glass of pop by absorbing heat from the pop as the ice melts.
 In most biological settings, temperature is measured on the Celsius scale (°C).
 At sea level, water freezes at 0°C and boils at 100°C.
 Human body temperature is typically 37°C.
 While there are several ways to measure heat energy, one convenient unit is the calorie
 One calorie is the amount of heat energy necessary to raise the temperature of one g of
water by 1°C.
 A calorie is released when 1 g of water cools by 1°C.
 In many biological processes, the kilocalorie (kcal) is more convenient.
Biology Chapter Notes
 A kilocalorie is the amount of heat energy necessary to raise the temperature of 1000 g
of water by 1°C.
 Another common energy unit, the joule (J), is equivalent to 0.239 cal.
 Water stabilizes temperature because it has a high specific heat.
 The specific heat of a substance is the amount of heat that must be absorbed or lost for 1
g of that substance to change its temperature by 1°C.
 By definition, the specific heat of water is 1 cal per gram per degree Celsius or 1
 Water has a high specific heat compared to other substances.
 For example, ethyl alcohol has a specific heat of 0.6 cal/g/°C.
 The specific heat of iron is 1/10 that of water.
 Water resists changes in temperature because of its high specific heat.
 In other words, water absorbs or releases a relatively large quantity of heat for each
degree of temperature change.
 Water’s high specific heat is due to hydrogen bonding.
 Heat must be absorbed to break hydrogen bonds, and heat is released when hydrogen
bonds form.
 Investment of one calorie of heat causes relatively little change to the temperature of
water because much of the energy is used to disrupt hydrogen bonds, not speed up the
movement of water molecules.
 Water’s high specific heat has effects that range from the level of the whole Earth to the
level of individual organisms.
 A large body of water can absorb a large amount of heat from the sun in daytime
during the summer and yet warm only a few degrees.
 At night and during the winter, the warm water will warm cooler air.
 Therefore, ocean temperatures and coastal land areas have more stable temperatures
than inland areas.
 Living things are made primarily of water. Consequently, they resist changes in
temperature better than they would if composed of a liquid with a lower specific heat.
 The transformation of a molecule from a liquid to a gas is called vaporization or
 This occurs when the molecule moves fast enough to overcome the attraction of other
molecules in the liquid.
 Even in a low-temperature liquid (with low average kinetic energy), some molecules
are moving fast enough to evaporate.
 Heating a liquid increases the average kinetic energy and increases the rate of
 Heat of vaporization is the quantity of heat that a liquid must absorb for 1 g of it to be
converted from liquid to gas.
 Water has a relatively high heat of vaporization, requiring about 580 cal of heat to
evaporate 1 g of water at room temperature.
 This is double the heat required to vaporize the same quantity of alcohol or ammonia.
 This is because hydrogen bonds must be broken before a water molecule can evaporate
from the liquid.
 Water’s high heat of vaporization moderates climate.

Biology Chapter Notes

 Much of the sun’s heat absorbed by tropical oceans is used for evaporation of surface
 As moist tropical air moves to the poles, water vapor condenses to form rain, releasing
 As a liquid evaporates, the surface of the liquid that remains behind cools, a phenomenon
called evaporative cooling.
 This occurs because the most energetic molecules are the most likely to evaporate,
leaving the lower–kinetic energy molecules behind.
 Evaporative cooling moderates temperature in lakes and ponds.
 Evaporation of sweat in mammals or evaporation of water from the leaves of plants
prevents terrestrial organisms from overheating.
 Evaporation of water from the leaves of plants or the skin of humans removes excess
Oceans and lakes don’t freeze solid because ice floats.
 Water is unusual because it is less dense as a solid than as a cold liquid.
 Most materials contract as they solidify, but water expands.
 At temperatures above 4°C, water behaves like other liquids, expanding as it warms
and contracting as it cools.
 Water begins to freeze when its molecules are no longer moving vigorously enough to
break their hydrogen bonds.
 When water reaches 0°C, water becomes locked into a crystalline lattice, with each water
molecule bonded to a maximum of four partners.
 As ice starts to melt, some of the hydrogen bonds break, and water molecules can slip
closer together than they can while in the ice state.
 Ice is about 10% less dense than water at 4°C.
 Therefore, ice floats on the cool water below.
 This oddity has important consequences for life.
 If ice sank, eventually all ponds, lakes, and even the ocean would freeze solid.
 During the summer, only the upper few centimeters of the ocean would thaw.
 Instead, the surface layer of ice insulates liquid water below, preventing it from
freezing and allowing life to exist under the frozen surface.
Water is the solvent of life.
 A liquid that is a completely homogeneous mixture of two or more substances is called a
 A sugar cube in a glass of water will eventually dissolve to form a uniform solution of
sugar and water.
 The dissolving agent is the solvent, and the substance that is dissolved is the solute.
 In our example, water is the solvent and sugar is the solute.
 In an aqueous solution, water is the solvent.
 Water is not a universal solvent, but it is very versatile because of the polarity of water
 Water is an effective solvent because it readily forms hydrogen bonds with charged
and polar covalent molecules.

Biology Chapter Notes

 For example, when a crystal of salt (NaCl) is placed in water, the Na + cations interact
with the partial negative charges of the oxygen regions of water molecules.

 The Cl anions interact with the partial positive charges of the hydrogen regions of
water molecules.
 Each dissolved ion is surrounded by a sphere of water molecules, a hydration shell.
 Eventually, water dissolves all the ions, resulting in a solution with two solutes: sodium
and chloride ions.
 Polar molecules are also soluble in water because they form hydrogen bonds with water.
 Even large molecules, like proteins, can dissolve in water if they have ionic and polar
 Any substance that has an affinity for water is hydrophilic (water-loving).
 These substances are dominated by ionic or polar bonds.
 Some hydrophilic substances do not dissolve because their molecules are too large.
 For example, cotton is hydrophilic because cellulose, its major constituent, has
numerous polar covalent bonds. However, its giant cellulose molecules are too large to
dissolve in water.
 Water molecules form hydrogen bonds with the cellulose fibers of cotton, allowing
you to dry yourself with your cotton towel as the water is pulled into the towel.
 Substances that have no affinity for water are hydrophobic (water-fearing).
 These substances are nonionic and have nonpolar covalent bonds.
 Because there are no consistent regions with partial or full charges, water molecules
cannot form hydrogen bonds with hydrophobic molecules.
 Oils such as vegetable oil are hydrophobic because the dominant bonds, carbon-carbon
and carbon-hydrogen, share electrons equally.
 Hydrophobic molecules are major ingredients of cell membranes.
 Biological chemistry is “wet” chemistry with most reactions involving solutes dissolved
in water.
 Chemical reactions depend on collisions of molecules and therefore on the concentrations
of solutes in aqueous solution.
 We measure the number of molecules in units called moles.
 The actual number of molecules in a mole is called Avogadro’s number, 6.02 × 10 23.
 A mole is equal to the molecular weight of a substance but scaled up from daltons to
 To illustrate, how could we measure out a mole of table sugar—sucrose (C12H22O11)?
 A carbon atom weighs 12 daltons, hydrogen 1 dalton, and oxygen 16 daltons.
 One molecule of sucrose would weigh 342 daltons, the sum of weights of all the atoms
in sucrose, or the molecular weight of sucrose.
 To get one mole of sucrose, we would weigh out 342 g.
 The advantage of using moles as a measurement is that a mole of one substance has the
same number of molecules as a mole of any other substance.
 If substance A has a molecular weight of 10 daltons and substance B has a molecular
weight of 100 daltons, then we know that 10 g of substance A has the same number of
molecules as 100 g of substance B.

Biology Chapter Notes

 A mole of sucrose contains 6.02 × 10 23 molecules23 and weighs 342 g, while a mole of
ethyl alcohol (C2H6O) also contains 6.02 × 10 molecules but weighs only 46 g
because the molecules are smaller.
 Measuring in moles allows scientists to combine substances in fixed ratios of
 In “wet” chemistry, we are typically combining solutions or measuring the quantities of
materials in aqueous solutions.
 The concentration of a material in solution is called its molarity.
 A one molar solution has one mole of a substance dissolved in one liter of solvent,
typically water.
 To make a 1 molar (1M) solution of sucrose, we would slowly add water to 342 g of
sucrose until the total volume was 1 liter and all the sugar was dissolved.

Concept 3.3 Dissociation of water molecules leads to acidic and basic conditions that
affect living organisms
 Occasionally, a hydrogen atom participating in a hydrogen bond between two water
molecules shifts from one molecule to the other.
 The hydrogen atom leaves its electron behind and is transferred as a single proton—a
hydrogen ion (H+).

 The water molecule that lost the proton is now a hydroxide ion (OH ).
 The water molecule with the extra proton is now a hydronium ion (H3O ).
 A simplified way to view this process is to say that a water molecule dissociates into a
hydrogen ion and a hydroxide ion:
+ −
 H2O <=> H + OH
 This reaction is reversible.
 At equilibrium, the concentration of water molecules greatly exceeds that of H+ and OH−.
 In pure water, only one water molecule in every 554 million is dissociated.
+ − −7 °
 At equilibrium, the concentration of H or OH is 10 M (at 25 C).
 Although the dissociation of water is reversible and statistically rare, it is very important
in the chemistry of life.
 Because hydrogen and hydroxide ions are very reactive, changes in their concentrations
can drastically affect the chemistry of a cell.
 Adding certain solutes, called acids and bases, disrupts the equilibrium and modifies the
concentrations of hydrogen and hydroxide ions.
 The pH scale is used to describe how acidic or basic a solution is.
Organisms are sensitive to changes in pH.
 An acid is a substance that increases the hydrogen ion concentration in a solution.
 When hydrochloric acid is added to water, hydrogen ions dissociate from chloride
ions: HCl -> H+ + Cl−
 Addition of an acid makes a solution more acidic.
 Any substance that reduces the hydrogen ion concentration in a solution is a base.
 Some bases reduce the H+ concentration directly by accepting hydrogen ions.
Biology Chapter Notes
 Ammonia (NH3) acts as a base when the nitrogen’s unshared electron pair attracts a
hydrogen ion from the solution, creating an ammonium ion (NH4+).
+ +
 NH3 + H <=> NH4
 Other bases reduce H+ indirectly by dissociating to OH−, which then combines with H+ to
form water.

 NaOH -> Na + OH
OH− + H+ -> H2O
 Solutions with more OH− than H+ are basic solutions.
 Solutions with more H+ than OH− are acidic solutions.
 Solutions in which concentrations of OH− and H+ are equal are neutral solutions.
 Some acids and bases (HCl and NaOH) are strong acids or bases.
 These molecules dissociate completely in water.
 Other acids and bases (NH3) are weak acids or bases.
 For these molecules, the binding and release of hydrogen ions are reversible.
 At equilibrium, there will be a fixed ratio of products to reactants.
 Carbonic acid (H2CO3) is a weak acid:
 H2CO3 <=> HCO3− + H+
 At equilibrium, 1% of the H2CO3 molecules will be dissociated.
 In any solution, the product of the H+ and OH− concentrations is constant at 10−14.
 Brackets ([H+] and [OH−]) indicate the molar concentration of the enclosed substance.
+ − −14
 [H ] [OH ] = 10
+ −7 − −7
 In a neutral solution, [H ] = 10 M and [OH ] = 10 M
 Adding acid to− a solution shifts the balance between H+ and OH− toward H+ and leads to a
decline in OH .
+ −5 − −9
 If [H ] = 10 M, then [OH ] = 10 M
 Hydroxide concentrations decline because some of the additional acid combines with
hydroxide to form water.
 Adding a base does the opposite, increasing OH − concentration and lowering H+
 The H+ and OH− concentrations of solutions can vary by a factor of 100 trillion or more.
 To express this variation more conveniently, the H+ and OH− concentrations are typically
expressed via the pH scale.
 The pH scale, ranging from 1 to 14, compresses the range of concentrations by
employing logarithms.
+ + −pH
 pH = − log [H ] or [H ] = 10
 In a neutral solution, [H+] = 10−7 M, and the pH = 7.
 Values for pH decline as [H+] increase.
 While the pH scale is based on [H+], values for [OH−] can be easily calculated from the
product relationship.
 The pH of a neutral solution is 7.
 Acidic solutions have pH values less than 7, and basic solutions have pH values greater
than 7.
 Most biological fluids have pH values in the range of 6 to 8.
Biology Chapter Notes
 However, the human stomach has strongly acidic digestive juice with a pH of about 2.
 Each pH unit represents a tenfold difference in H+ and OH− concentrations.
+ −
 A small change in pH actually indicates a substantial change in H and OH
 The chemical processes in the cell can be disrupted by changes to the H + and OH−
concentrations away from their normal values, usually near pH 7.
 To maintain cellular pH values at a constant level, biological fluids have buffers.
 Buffers resist changes to the pH of a solution when H+ or OH− is added to the solution.
 Buffers accept hydrogen ions from the solution when they are in excess and donate
hydrogen ions when they have been depleted.
 Buffers typically consist of a weak acid and its corresponding base.
 One important buffer in human blood and other biological solutions is carbonic acid,
which dissociates to yield a bicarbonate ion and a hydrogen ion.
 The chemical equilibrium between carbonic acid and bicarbonate acts as a pH
regulator. +The equilibrium shifts left or right as other metabolic processes add or
remove H from the solution.
Acid precipitation threatens the fitness of the environment.
 Acid precipitation is a serious assault on water quality in some industrialized areas.
 Uncontaminated rain has a slightly acidic pH of 5.6.
 The acid is a product of the formation of carbonic acid from carbon dioxide and water.
 Acid precipitation occurs when rain, snow, or fog has a pH that is more acidic than 5.6.
 Acid precipitation is caused primarily by sulfur oxides and nitrogen oxides in the
 These molecules react with water to form strong acids that fall to the surface with rain
or snow.
 The major source of these oxides is the burning of fossil fuels (coal, oil, and gas) in
factories and automobiles.
 The presence of tall smokestacks allows this pollution to spread from its site of origin to
contaminate relatively pristine areas thousands of kilometers away.
 In 2001, rain in the Adirondack Mountains of upstate New York had an average pH of
 The effects of acids in lakes and streams are more pronounced in the spring during
 As the surface snows melt and drain down through the snowfield, the meltwater
accumulates acid and brings it into lakes and streams all at once.
 The pH of early meltwater may be as low as 3.
 Acid precipitation has a great impact on the eggs and the early developmental stages of
aquatic organisms that are abundant in the spring.
 Thus, strong acidity can alter the structure of molecules and impact ecological
 Direct impacts of acid precipitation on forests and terrestrial life are more controversial.
 However, acid precipitation can impact soils by affecting the solubility of soil minerals.
 Acid precipitation can wash away key soil buffers and plant nutrients such as calcium
and magnesium ions.
Biology Chapter Notes
 It can also increase the concentrations of compounds such as aluminum to toxic levels.
 This has done major damage to forests in Europe and substantial damage of forests in
North America.
 Progress has been made in reducing acid precipitation.

Biology Chapter Notes

Chapter 4 Carbon and the Molecular Diversity of Life
Chapter Notes
Overview: Carbon – The Backbone of Biological Molecules
· Although cells are 70–95% water, the rest consists mostly of carbon-based compounds.
· Carbon is unparalleled in its ability to form large, complex, and diverse molecules.
· Carbon accounts for the diversity of biological molecules and has made possible the great diversity of
living things.
· Proteins, DNA, carbohydrates, and other molecules that distinguish living matter from inorganic material
are all composed of carbon atoms bonded to each other and to atoms of other elements.
· These other elements commonly include hydrogen (H), oxygen (O), nitrogen (N), sulfur (S), and
phosphorus (P).

Concept 4.1 Organic chemistry is the study of carbon compounds

· The study of carbon compounds, organic chemistry, deals with any compound with carbon (organic
· Organic compounds can range from simple molecules, such as CO2 or CH4, to complex molecules such
as proteins, which may weigh more than 100,000 daltons.
· The overall percentages of the major elements of life (C, H, O, N, S, and P) are quite uniform from one
organism to another.
· However, because of carbon’s versatility, these few elements can be combined to build an inexhaustible
variety of organic molecules.
· Variations in organic molecules can distinguish even between individuals of a single species.
· The science of organic chemistry began in attempts to purify and improve the yield of products obtained
from other organisms.
· Initially, chemists learned to synthesize simple compounds in the laboratory, but had no success with
more complex compounds.
· The Swedish chemist Jons Jacob Berzelius was the first to make a distinction between organic
compounds that seemed to arise only in living organisms and inorganic compounds that were found in the
nonliving world.
· This led early organic chemists to propose vitalism, the belief that physical and chemical laws did not
apply to living things.
· Support for vitalism began to wane as organic chemists learned to synthesize complex organic
compounds in the laboratory.
Biology Chapter Notes
· In the early 1800s, the German chemist Friedrich Wöhler and his students were able to synthesize urea
from totally inorganic materials.
· In 1953, Stanley Miller at the University of Chicago set up a laboratory simulation of chemical
conditions on the primitive Earth and demonstrated the spontaneous synthesis of organic compounds.
· Such spontaneous synthesis of organic compounds may have been an early stage in the origin of life.
· Organic chemists finally rejected vitalism and embraced mechanism, accepting that the same physical
and chemical laws govern all natural phenomena including the processes of life.
· Organic chemistry was redefined as the study of carbon compounds regardless of their origin.
· Organisms do produce the majority of organic compounds.
· The laws of chemistry apply to inorganic and organic compounds alike.

Concept 4.2 Carbon atoms can form diverse molecules by bonding to four other atoms
· With a total of 6 electrons, a carbon atom has 2 in the first electron shell and 4 in the second shell.
· Carbon has little tendency to form ionic bonds by losing or gaining 4 electrons to complete its valence
· Instead, carbon usually completes its valence shell by sharing electrons with other atoms in four covalent
· This tetravalence by carbon makes large, complex molecules possible.
· When carbon forms covalent bonds with four other atoms, they are arranged at the corners of an
imaginary tetrahedron with bond angles of 109.5°.
· In molecules with multiple carbons, every carbon bonded to four other atoms has a tetrahedral shape.
· However, when two carbon atoms are joined by a double bond, all bonds around those carbons are in the
same plane and have a flat, three-dimensional structure.
· The three-dimensional shape of an organic molecule determines its function.
· The electron configuration of carbon makes it capable of forming covalent bonds with many different
· The valences of carbon and its partners can be viewed as the building code that governs the architecture
of organic molecules.
· In carbon dioxide, one carbon atom forms two double bonds with two different oxygen atoms.
· In the structural formula, O=C=O, each line represents a pair of shared electrons. This arrangement
completes the valence shells of all atoms in the molecule.
· While CO2 can be classified as either organic or inorganic, its importance to the living world is clear.
Biology Chapter Notes
· CO2 is the source of carbon for all organic molecules found in organisms. It is usually fixed into organic
molecules by the process of photosynthesis.
· Urea, CO(NH2)2, is another simple organic molecule in which each atom forms covalent bonds to
complete its valence shell.
Variation in carbon skeletons contributes to the diversity of organic molecules.
· Carbon chains form the skeletons of most organic molecules.
· The skeletons vary in length and may be straight, branched, or arranged in closed rings.
· The carbon skeletons may include double bonds.
· Atoms of other elements can be bonded to the atoms of the carbon skeleton.
· Hydrocarbons are organic molecules that consist of only carbon and hydrogen atoms.
· Hydrocarbons are the major component of petroleum, a fossil fuel that consists of the partially
decomposed remains of organisms that lived millions of years ago.
· Fats are biological molecules that have long hydrocarbon tails attached to a nonhydrocarbon component.
· Petroleum and fat are hydrophobic compounds that cannot dissolve in water because of their many
nonpolar carbon-to-hydrogen bonds.
· Isomers are compounds that have the same molecular formula but different structures and, therefore,
different chemical properties.
· For example, butane and isobutane have the same molecular formula, C4H10, but butane has a straight
skeleton and isobutane has a branched skeleton.
· The two butanes are structural isomers, molecules that have the same molecular formula but differ in
the covalent arrangement of atoms.
· Geometric isomers are compounds with the same covalent partnerships that differ in the spatial
arrangement of atoms around a carbon–carbon double bond.
· The double bond does not allow atoms to rotate freely around the bond axis.
· The biochemistry of vision involves a light-induced change in the structure of rhodopsin in the retina
from one geometric isomer to another.
· Enantiomers are molecules that are mirror images of each other.
· Enantiomers are possible when four different atoms or groups of atoms are bonded to a carbon.
· In this case, the four groups can be arranged in space in two different ways that are mirror images.
· They are like left-handed and right-handed versions of the molecule.
· Usually one is biologically active, while the other is inactive.

Biology Chapter Notes

· Even subtle structural differences in two enantiomers have important functional significance because of
emergent properties from specific arrangements of atoms.
· One enantiomer of the drug thalidomide reduced morning sickness, the desired effect, but the other
isomer caused severe birth defects.
· The L-dopa isomer is an effective treatment of Parkinson’s disease, but the D-dopa isomer is inactive.

Concept 4.3 Functional groups are the parts of molecules involved in chemical reactions
· The components of organic molecules that are most commonly involved in chemical reactions are known
as functional groups.
· If we consider hydrocarbons to be the simplest organic molecules, we can view functional groups as
attachments that replace one or more of the hydrogen atoms bonded to the carbon skeleton of the
· Each functional group behaves consistently from one organic molecule to another.
· The number and arrangement of functional groups help give each molecule its unique properties.
· As an example, the basic structure of testosterone (a male sex hormone) and estradiol (a female sex
hormone) is the same.
· Both are steroids with four fused carbon rings, but they differ in the functional groups attached to the
· These functional groups interact with different targets in the body.
· There are six functional groups that are most important to the chemistry of life: hydroxyl, carbonyl,
carboxyl, amino, sulfhydryl, and phosphate groups.
· All are hydrophilic and increase the solubility of organic compounds in water.
· In a hydroxyl group (—OH), a hydrogen atom forms a polar covalent bond with an oxygen atom, which
forms a polar covalent bond to the carbon skeleton.
· Because of these polar covalent bonds, hydroxyl groups increase the solubility of organic molecules.
· Organic compounds with hydroxyl groups are alcohols, and their names typically end in -ol.
· A carbonyl group (>CO) consists of an oxygen atom joined to the carbon skeleton by a double bond.
· If the carbonyl group is on the end of the skeleton, the compound is an aldehyde.
· If the carbonyl group is within the carbon skeleton, then the compound is a ketone.
· Isomers with aldehydes versus ketones have different properties.
· A carboxyl group (—COOH) consists of a carbon atom with a double bond to an oxygen atom and a
single bond to the oxygen of a hydroxyl group.
Biology Chapter Notes
· Compounds with carboxyl groups are carboxylic acids.
· A carboxyl group acts as an acid because the combined electronegativities of the two adjacent oxygen
atoms increase the dissociation of hydrogen as an ion (H+).
· An amino group (—NH2) consists of a nitrogen atom bonded to two hydrogen atoms and the carbon
· Organic compounds with amino groups are amines.
· The amino group acts as a base because the amino group can pick up a hydrogen ion (H+) from the
· Amino acids, the building blocks of proteins, have amino and carboxyl groups.
· A sulfhydryl group (—SH) consists of a sulfur atom bonded to a hydrogen atom and to the backbone.
· This group resembles a hydroxyl group in shape.
· Organic molecules with sulfhydryl groups are thiols.
· Two sulfhydryl groups can interact to help stabilize the structure of proteins.
· A phosphate group (—OPO32−) consists of a phosphorus atom bound to four oxygen atoms (three with
single bonds and one with a double bond).
· A phosphate group connects to the carbon backbone via one of its oxygen atoms.
· Phosphate groups are anions with two negative charges, as two protons have dissociated from the
oxygen atoms.
· One function of phosphate groups is to transfer energy between organic molecules.
· Adenosine triphosphate, or ATP, is the primary energy-transferring molecule in living cells.
These are the chemical elements of life.
· Living matter consists mainly of carbon, oxygen, hydrogen, and nitrogen, with smaller amounts of sulfur
and phosphorus.
· These elements are linked by strong covalent bonds.
· Carbon, with its four covalent bonds, is the basic building block in molecular architecture.
· The great diversity of organic molecules with their special properties emerges from the unique
arrangement of the carbon skeleton and the functional groups attached to the skeleton.

Biology Chapter Notes

Chapter 5 The Structure and Function of
Chapter Notes

Overview: The Molecules of Life

 Within cells, small organic molecules are joined together to form larger molecules.
 These large macromolecules may consist of thousands of covalently bonded atoms and
weigh more than 100,000 daltons.
 The four major classes of macromolecules are carbohydrates, lipids, proteins, and nucleic

Concept 5.1 Most macromolecules are polymers, built from monomers

 Three of the four classes of macromolecules—carbohydrates, proteins, and nucleic
acids—form chainlike molecules called polymers.
 A polymer is a long molecule consisting of many similar or identical building blocks
linked by covalent bonds.
 The repeated units are small molecules called monomers.
 Some of the molecules that serve as monomers have other functions of their own.
 The chemical mechanisms that cells use to make and break polymers are similar for all
classes of macromolecules.
 Monomers are connected by covalent bonds that form through the loss of a water
molecule. This reaction is called a condensation reaction or dehydration reaction.
 When a bond forms between two monomers, each monomer contributes part of the
water molecule that is lost. One monomer provides a hydroxyl group (—OH), while
the other provides a hydrogen (—H).
 Cells invest energy to carry out dehydration reactions.
 The process is aided by enzymes.
 The covalent bonds connecting monomers in a polymer are disassembled by hydrolysis, a
reaction that is effectively the reverse of dehydration.
 In hydrolysis, bonds are broken by the addition of water molecules. A hydrogen atom
attaches to one monomer, and a hydroxyl group attaches to the adjacent monomer.
 Our food is taken in as organic polymers that are too large for our cells to absorb.
Within the digestive tract, various enzymes direct hydrolysis of specific polymers. The
resulting monomers are absorbed by the cells lining the gut and transported to the
bloodstream for distribution to body cells.
 The body cells then use dehydration reaction to assemble the monomers into new
polymers that carry out functions specific to the particular cell type.
An immense variety of polymers can be built from a small set of monomers.
 Each cell has thousands of different kinds of macromolecules.
 These molecules vary among cells of the same individual. They vary more among
unrelated individuals of a species, and even more between species.
Biology Chapter Notes
 This diversity comes from various combinations of the 40–50 common monomers and
some others that occur rarely.
 These monomers can be connected in a great many combinations, just as the 26 letters
in the alphabet can be used to create a great diversity of words.

Concept 5.2 Carbohydrates serve as fuel and building material

 Carbohydrates include sugars and their polymers.
 The simplest carbohydrates are monosaccharides, or simple sugars.
 Disaccharides, or double sugars, consist of two monosaccharides joined by a condensation
 Polysaccharides are polymers of many monosaccharides.
Sugars, the smallest carbohydrates, serve as fuel and a source of carbon.
 Monosaccharides generally have molecular formulas that are some multiple of the unit
 For example, glucose has the formula C6H12O6.
 Monosaccharides have a carbonyl group (>C=O) and multiple hydroxyl groups (—OH).
 Depending on the location of the carbonyl group, the sugar is an aldose or a ketose.
 Most names for sugars end in -ose.
 Glucose, an aldose, and fructose, a ketose, are structural isomers.
 Monosaccharides are also classified by the number of carbons in the carbon skeleton.
 Glucose and other six-carbon sugars are hexoses.
 Five-carbon backbones are pentoses; three-carbon sugars are trioses.
 Monosaccharides may also exist as enantiomers.
 For example, glucose and galactose, both six-carbon aldoses, differ in the spatial
arrangement of their parts around asymmetrical carbons.
 Monosaccharides, particularly glucose, are a major fuel for cellular work.
 They also function as the raw material for the synthesis of other monomers, such as amino
acids and fatty acids.
 While often drawn as a linear skeleton, monosaccharides in aqueous solutions form rings.
 Two monosaccharides can join with a glycosidic linkage to form a disaccharide via
 Maltose, malt sugar, is formed by joining two glucose molecules.
 Sucrose, table sugar, is formed by joining glucose and fructose. Sucrose is the major
transport form of sugars in plants.
 Lactose, milk sugar, is formed by joining glucose and galactose.
Polysaccharides, the polymers of sugars, have storage and structural roles.
 Polysaccharides are polymers of hundreds to thousands of monosaccharides joined by
glycosidic linkages.
 Some polysaccharides serve for storage and are hydrolyzed as sugars are needed.
 Other polysaccharides serve as building materials for the cell or the whole organism.

Biology Chapter Notes

 Starch is a storage polysaccharide composed entirely of glucose monomers.
 Most of these monomers are joined by 1–4 linkages (number 1 carbon to number 4
carbon) between the glucose molecules.
 The simplest form of starch, amylose, is unbranched and forms a helix.
 Branched forms such as amylopectin are more complex.
 Plants store surplus glucose as starch granules within plastids, including chloroplasts, and
withdraw it as needed for energy or carbon.
 Animals that feed on plants, especially parts rich in starch, have digestive enzymes that
can hydrolyze starch to glucose.
 Animals store glucose in a polysaccharide called glycogen.
 Glycogen is highly branched like amylopectin.
 Humans and other vertebrates store a day’s supply of glycogen in the liver and
 Cellulose is a major component of the tough wall of plant cells.
 Plants produce almost one hundred billion tons of cellulose per year. It is the most
abundant organic compound on Earth.
 Like starch, cellulose is a polymer of glucose. However, the glycosidic linkages in these
two polymers differ.
 The difference is based on the fact that there are actually two slightly different ring
structures for glucose.
 These two ring forms differ in whether the hydroxyl group attached to the number 1
carbon is fixed above (beta glucose) or below (alpha glucose) the plane of the ring.
 Starch is a polysaccharide of alpha glucose monomers.
 Cellulose is a polysaccharide of beta glucose monomers, making every other glucose
monomer upside down with respect to its neighbors.
 The differing glycosidic links in starch and cellulose give the two molecules distinct
three-dimensional shapes.
 While polymers built with alpha glucose form helical structures, polymers built with
beta glucose form straight structures.
 The straight structures built with beta glucose allow H atoms on one strand to form
hydrogen bonds with OH groups on other strands.
 In plant cell walls, parallel cellulose molecules held together in this way are grouped
into units called microfibrils, which form strong building materials for plants (and for
humans, as lumber).
 The enzymes that digest starch by hydrolyzing its alpha linkages cannot hydrolyze the
beta linkages in cellulose.
 Cellulose in human food passes through the digestive tract and is eliminated in feces as
“insoluble fiber.”
 As it travels through the digestive tract, cellulose abrades the intestinal walls and
stimulates the secretion of mucus, aiding in the passage of food.
 Some microbes can digest cellulose to its glucose monomers through the use of cellulase
 Many eukaryotic herbivores, from cows to termites, have symbiotic relationships with
cellulolytic microbes, providing the microbe and the host animal access to a rich source of
 Some fungi can also digest cellulose.
Biology Chapter Notes
 Another important structural polysaccharide is chitin, used in the exoskeletons of
arthropods (including insects, spiders, and crustaceans).
 Chitin is similar to cellulose, except that it contains a nitrogen-containing appendage
on each glucose monomer.
 Pure chitin is leathery but can be hardened by the addition of calcium carbonate.
 Chitin also provides structural support for the cell walls of many fungi.

Concept 5.3 Lipids are a diverse group of hydrophobic molecules

 Unlike other macromolecules, lipids do not form polymers.
 The unifying feature of lipids is that they all have little or no affinity for water.
 This is because they consist mostly of hydrocarbons, which form nonpolar covalent
 Lipids are highly diverse in form and function.
Fats store large amounts of energy.
 Although fats are not strictly polymers, they are large molecules assembled from smaller
molecules by dehydration reactions.
 A fat is constructed from two kinds of smaller molecules: glycerol and fatty acids.
 Glycerol is a three-carbon alcohol with a hydroxyl group attached to each carbon.
 A fatty acid consists of a carboxyl group attached to a long carbon skeleton, often 16
to 18 carbons long.
 The many nonpolar C—H bonds in the long hydrocarbon skeleton make fats
 Fats separate from water because the water molecules hydrogen bond to one another
and exclude the fats.
 In a fat, three fatty acids are joined to glycerol by an ester linkage, creating a
triacylglycerol, or triglyceride.
 The three fatty acids in a fat can be the same or different.
 Fatty acids may vary in length (number of carbons) and in the number and locations of
double bonds.
 If the fatty acid has no carbon-carbon double bonds, then the molecule is a saturated
fatty acid, saturated with hydrogens at every possible position.
 If the fatty acid has one or more carbon-carbon double bonds formed by the removal of
hydrogen atoms from the carbon skeleton, then the molecule is an unsaturated fatty
 A saturated fatty acid is a straight chain, but an unsaturated fatty acid has a kink wherever
there is a double bond.
 Fats made from saturated fatty acids are saturated fats.
 Most animal fats are saturated.
 Saturated fats are solid at room temperature.
 Fats made from unsaturated fatty acids are unsaturated fats.
 Plant and fish fats are liquid at room temperature and are known as oils.

Biology Chapter Notes

 The kinks caused by the double bonds prevent the molecules from packing tightly
enough to solidify at room temperature.
 The phrase “hydrogenated vegetable oils” on food labels means that unsaturated fats
have been synthetically converted to saturated fats by the addition of hydrogen.
 Peanut butter and margarine are hydrogenated to prevent lipids from separating out
as oil.
 A diet rich in saturated fats may contribute to cardiovascular disease (atherosclerosis)
through plaque deposits.
 The process of hydrogenating vegetable oils produces saturated fats and also
unsaturated fats with trans double bonds. These trans fat molecules contribute more
than saturated fats to atherosclerosis.
 The major function of fats is energy storage.
 A gram of fat stores more than twice as much energy as a gram of a polysaccharide
such as starch.
 Because plants are immobile, they can function with bulky energy storage in the form
of starch. Plants use oils when dispersal and compact storage is important, as in seeds.
 Animals must carry their energy stores with them and benefit from having a more
compact fuel reservoir of fat.
 Humans and other mammals store fats as long-term energy reserves in adipose cells
that swell and shrink as fat is deposited or withdrawn from storage.
 Adipose tissue also functions to cushion vital organs, such as the kidneys.
 A layer of fat can also function as insulation.
 This subcutaneous layer is especially thick in whales, seals, and most other marine
Phospholipids are major components of cell membranes.
 Phospholipids have two fatty acids attached to glycerol and a phosphate group at the
third position.
 The phosphate group carries a negative charge.
 Additional smaller groups may be attached to the phosphate group to form a variety of
 The interaction of phospholipids with water is complex.
 The fatty acid tails are hydrophobic, but the phosphate group and its attachments form
a hydrophilic head.
 When phospholipids are added to water, they self-assemble into assemblages with the
hydrophobic tails pointing toward the interior.
 This type of structure is called a micelle.
 Phospholipids are arranged as a bilayer at the surface of a cell.
 Again, the hydrophilic heads are on the outside of the bilayer, in contact with the
aqueous solution, and the hydrophobic tails point toward the interior of the bilayer.
 The phospholipid bilayer forms a barrier between the cell and the external
 Phospholipids are the major component of all cell membranes.
Steroids include cholesterol and certain hormones.
 Steroids are lipids with a carbon skeleton consisting of four fused rings.
 Different steroids are created by varying functional groups attached to the rings.
Biology Chapter Notes
 Cholesterol, an important steroid, is a component in animal cell membranes.
 Cholesterol is also the precursor from which all other steroids are synthesized.
 Many of these other steroids are hormones, including the vertebrate sex hormones.
 While cholesterol is an essential molecule in animals, high levels of cholesterol in the
blood may contribute to cardiovascular disease.
 Both saturated fats and trans fats exert their negative impact on health by affecting
cholesterol levels.

Concept 5.4 Proteins have many structures, resulting in a wide range of functions
 Proteins account for more than 50% of the dry mass of most cells. They are instrumental
in almost everything that an organism does.
 Protein functions include structural support, storage, transport, cellular signaling,
movement, and defense against foreign substances.
 Most important, protein enzymes function as catalysts in cells, regulating metabolism
by selectively accelerating chemical reactions without being consumed.
 Humans have tens of thousands of different proteins, each with a specific structure and
 Proteins are the most structurally complex molecules known.
 Each type of protein has a complex three-dimensional shape or conformation.
 All protein polymers are constructed from the same set of 20 amino acid monomers.
 Polymers of proteins are called polypeptides.
 A protein consists of one or more polypeptides folded and coiled into a specific
Amino acids are the monomers from which proteins are constructed.
 Amino acids are organic molecules with both carboxyl and amino groups.
 At the center of an amino acid is an asymmetric carbon atom called the alpha carbon.
 Four components are attached to the alpha carbon: a hydrogen atom, a carboxyl group, an
amino group, and a variable R group (or side chain).
 Different R groups characterize the 20 different amino acids.
 R groups may be as simple as a hydrogen atom (as in the amino acid glycine), or it may
be a carbon skeleton with various functional groups attached (as in glutamine).
 The physical and chemical properties of the R group determine the unique characteristics
of a particular amino acid.
 One group of amino acids has hydrophobic R groups.
 Another group of amino acids has polar R groups that are hydrophilic.
 A third group of amino acids includes those with functional groups that are charged
(ionized) at cellular pH.
 Some acidic R groups are negative in charge due to the presence of a carboxyl
 Basic R groups have amino groups that are positive in charge.
 Note that all amino acids have carboxyl and amino groups. The terms acidic and
basic in this context refer only to these groups in the R groups.
Biology Chapter Notes
 Amino acids are joined together when a dehydration reaction removes a hydroxyl group
from the carboxyl end of one amino acid and a hydrogen from the amino group of
 The resulting covalent bond is called a peptide bond.
 Repeating the process over and over creates a polypeptide chain.
 At one end is an amino acid with a free amino group (the N-terminus) and at the other
is an amino acid with a free carboxyl group (the C-terminus).
 Polypeptides range in size from a few monomers to thousands.
 Each polypeptide has a unique linear sequence of amino acids.
The amino acid sequence of a polypeptide can be determined.
 Frederick Sanger and his colleagues at Cambridge University determined the amino acid
sequence of insulin in the 1950s.
 Sanger used protein-digesting enzymes and other catalysts to hydrolyze the insulin at
specific places.
 The fragments were then separated by a technique called chromatography.
 Hydrolysis by another agent broke the polypeptide at different sites, yielding a second
group of fragments.
 Sanger used chemical methods to determine the sequence of amino acids in the small
 He then searched for overlapping regions among the pieces obtained by hydrolyzing
with the different agents.
 After years of effort, Sanger was able to reconstruct the complete primary structure of
 Most of the steps in sequencing a polypeptide have since been automated.
Protein conformation determines protein function.
 A functional protein consists of one or more polypeptides that have been twisted, folded,
and coiled into a unique shape.
 It is the order of amino acids that determines what the three-dimensional conformation of
the protein will be.
 A protein’s specific conformation determines its function.
 When a cell synthesizes a polypeptide, the chain generally folds spontaneously to assume
the functional conformation for that protein.
 The folding is reinforced by a variety of bonds between parts of the chain, which in turn
depend on the sequence of amino acids.
 Many proteins are globular, while others are fibrous in shape.
 In almost every case, the function of a protein depends on its ability to recognize and bind
to some other molecule.
 For example, an antibody binds to a particular foreign substance.
 An enzyme recognizes and binds to a specific substrate, facilitating a chemical
 Natural signal molecules called endorphins bind to specific receptor proteins on the
surface of brain cells in humans, producing euphoria and relieving pain.
 Morphine, heroin, and other opiate drugs mimic endorphins because they are
similar in shape and can bind to the brain’s endorphin receptors.
Biology Chapter Notes
 The function of a protein is an emergent property resulting from its specific molecular
 Three levels of structure—primary, secondary, and tertiary structures—organize the
folding within a single polypeptide.
 Quaternary structure arises when two or more polypeptides join to form a protein.
 The primary structure of a protein is its unique sequence of amino acids.
 Lysozyme, an enzyme that attacks bacteria, consists of 129 amino acids.
 The precise primary structure of a protein is determined by inherited genetic
 Even a slight change in primary structure can affect a protein’s conformation and ability
to function.
 The substitution of one amino acid (valine) for the normal one (glutamic acid) at a
particular position in the primary structure of hemoglobin, the protein that carries
oxygen in red blood cells, can cause sickle-cell disease, an inherited blood disorder.
 The abnormal hemoglobins crystallize, deforming the red blood cells into a sickle
shape and clogging capillaries.
 Most proteins have segments of their polypeptide chains repeatedly coiled or folded.
 These coils and folds are referred to as secondary structure and result from hydrogen
bonds between the repeating constituents of the polypeptide backbone.
 The weakly positive hydrogen atom attached to the nitrogen atom has an affinity for
the oxygen atom of a nearby peptide bond.
 Each hydrogen bond is weak, but the sum of many hydrogen bonds stabilizes the
structure of part of the protein.
 Typical secondary structures are coils (an alpha helix) or folds (beta pleated sheets).
 The structural properties of silk are due to beta pleated sheets.
 The presence of so many hydrogen bonds makes each silk fiber stronger than a steel
strand of the same weight.
 Tertiary structure is determined by interactions among various R groups.
 These interactions include hydrogen bonds between polar and/or charged areas, ionic
bonds between charged R groups, and hydrophobic interactions and van der Waals
interactions among hydrophobic R groups.
 While these three interactions are relatively weak, strong covalent bonds called
disulfide bridges that form between the sulfhydryl groups (SH) of two cysteine
monomers act to rivet parts of the protein together.
 Quaternary structure results from the aggregation of two or more polypeptide subunits.
 Collagen is a fibrous protein of three polypeptides that are supercoiled like a rope.
 This provides structural strength for collagen’s role in connective tissue.
 Hemoglobin is a globular protein with quaternary structure.
 It consists of four polypeptide subunits: two alpha and two beta chains.
 Both types of subunits consist primarily of alpha-helical secondary structure.
 Each subunit has a nonpeptide heme component with an iron atom that binds oxygen.
 What are the key factors determining protein conformation?
 A polypeptide chain of a given amino acid sequence can spontaneously arrange itself into
a 3D shape determined and maintained by the interactions responsible for secondary and
tertiary structure.
Biology Chapter Notes
 The folding occurs as the protein is being synthesized within the cell.
 However, protein conformation also depends on the physical and chemical conditions of
the protein’s environment.
 Alterations in pH, salt concentration, temperature, or other factors can unravel or
denature a protein.
 These forces disrupt the hydrogen bonds, ionic bonds, and disulfide bridges that
maintain the protein’s shape.
 Most proteins become denatured if the are transferred to an organic solvent. The
polypeptide chain refolds so that its hydrophobic regions face outward, toward the
 Denaturation can also be caused by heat, which disrupts the weak interactions that
stabilize conformation.
 This explains why extremely high fevers can be fatal. Proteins in the blood become
denatured by the high body temperatures.
 Some proteins can return to their functional shape after denaturation, but others cannot,
especially in the crowded environment of the cell.
 Biochemists now know the amino acid sequences of more than 875,000 proteins and the
3D shapes of about 7,000.
 Nevertheless, it is still difficult to predict the conformation of a protein from its
primary structure alone.
 Most proteins appear to undergo several intermediate stages before reaching their
“mature” configuration.
 The folding of many proteins is assisted by chaperonins or chaperone proteins.
 Chaperonins do not specify the final structure of a polypeptide but rather work to
segregate and protect the polypeptide while it folds spontaneously.
 At present, scientists use X-ray crystallography to determine protein conformation.
 This technique requires the formation of a crystal of the protein being studied.
 The pattern of diffraction of an X-ray by the atoms of the crystal can be used to determine
the location of the atoms and to build a computer model of its structure.
 Nuclear magnetic resonance (NMR) spectroscopy has recently been applied to this
 This method does not require protein crystallization.

Concept 5.5 Nucleic acids store and transmit hereditary information

 The amino acid sequence of a polypeptide is programmed by a unit of inheritance known
as a gene.
 A gene consists of DNA, a polymer known as a nucleic acid.
There are two types of nucleic acids: RNA and DNA.
 There are two types of nucleic acids: ribonucleic acid (RNA) and deoxyribonucleic acid
 These are the molecules that allow living organisms to reproduce their complex
components from generation to generation.
 DNA provides directions for its own replication.
Biology Chapter Notes
 DNA also directs RNA synthesis and, through RNA, controls protein synthesis.
 Organisms inherit DNA from their parents.
 Each DNA molecule is very long, consisting of hundreds to thousands of genes.
 Before a cell reproduces itself by dividing, its DNA is copied. The copies are then
passed to the next generation of cells.
 While DNA encodes the information that programs all the cell’s activities, it is not
directly involved in the day-to-day operations of the cell.
 Proteins are responsible for implementing the instructions contained in DNA.
 Each gene along a DNA molecule directs the synthesis of a specific type of messenger
RNA molecule (mRNA).
 The mRNA molecule interacts with the cell’s protein-synthesizing machinery to direct the
ordering of amino acids in a polypeptide.
 The flow of genetic information is from DNA -> RNA -> protein.
 Protein synthesis occurs on cellular structures called ribosomes.
 In eukaryotes, DNA is located in the nucleus, but most ribosomes are in the cytoplasm.
mRNA functions as an intermediary, moving information and directions from the nucleus
to the cytoplasm.
 Prokaryotes lack nuclei but still use RNA as an intermediary to carry a message from
DNA to the ribosomes.
A nucleic acid strand is a polymer of nucleotides.
 Nucleic acids are polymers made of nucleotide monomers.
 Each nucleotide consists of three parts: a nitrogenous base, a pentose sugar, and a
phosphate group.
 The nitrogen bases are rings of carbon and nitrogen that come in two types: purines and
 Pyrimidines have a single six-membered ring.
 There are three different pyrimidines: cytosine (C), thymine (T), and uracil (U).
 Purines have a six-membered ring joined to a five-membered ring.
 The two purines are adenine (A) and guanine (G).
 The pentose joined to the nitrogen base is ribose in nucleotides of RNA and deoxyribose
in DNA.
 The only difference between the sugars is the lack of an oxygen atom on carbon two in
 Because the atoms in both the nitrogenous base and the sugar are numbered, the sugar
atoms have a prime after the number to distinguish them.
 Thus, the second carbon in the sugar ring is the 2’ (2 prime) carbon and the carbon that
sticks up from the ring is the 5’ carbon.
 The combination of a pentose and a nitrogenous base is a nucleoside.
 The addition of a phosphate group creates a nucleoside monophosphate or nucleotide.
 Polynucleotides are synthesized when adjacent nucleotides are joined by covalent bonds
called phosphodiester linkages that form between the —OH group on the 3’ of one
nucleotide and the phosphate on the 5’ carbon of the next.
 This creates a repeating backbone of sugar-phosphate units, with appendages
consisting of the nitrogenous bases.
Biology Chapter Notes
 The two free ends of the polymer are distinct.
 One end has a phosphate attached to a 5’ carbon; this is the 5’ end.
 The other end has a hydroxyl group on a 3’ carbon; this is the 3’ end.
 The sequence of bases along a DNA or mRNA polymer is unique for each gene.
 Because genes are normally hundreds to thousands of nucleotides long, the number of
possible base combinations is virtually limitless.
 The linear order of bases in a gene specifies the order of amino acids—the primary
structure—of a protein, which in turn determines three-dimensional conformation and
Inheritance is based on replication of the DNA double helix.
 An RNA molecule is a single polynucleotide chain.
 DNA molecules have two polynucleotide strands that spiral around an imaginary axis to
form a double helix.
 The double helix was first proposed as the structure of DNA in 1953 by James Watson
and Francis Crick.
 The sugar-phosphate backbones of the two polynucleotides are on the outside of the helix.
 The two backbones run in opposite 5’ -> 3’ directions from each other, an arrangement
referred to as antiparallel.
 Pairs of nitrogenous bases, one from each strand, connect the polynucleotide chains with
hydrogen bonds.
 Most DNA molecules have thousands to millions of base pairs.
 Because of their shapes, only some bases are compatible with each other.
 Adenine (A) always pairs with thymine (T) and guanine (G) with cytosine (C).
 With these base-pairing rules, if we know the sequence of bases on one strand, we know
the sequence on the opposite strand.
 The two strands are complementary.
 Prior to cell division, each of the strands serves as a template to order nucleotides into a
new complementary strand.
 This results in two identical copies of the original double-stranded DNA molecule,
which are then distributed to the daughter cells.
 This mechanism ensures that a full set of genetic information is transmitted whenever a
cell reproduces.
We can use DNA and proteins as tape measures of evolution.
 Genes (DNA) and their products (proteins) document the hereditary background of an
 Because DNA molecules are passed from parents to offspring, siblings have greater
similarity in their DNA and protein than do unrelated individuals of the same species.
 This argument can be extended to develop a “molecular genealogy” to relationships
between species.
 Two species that appear to be closely related based on fossil and molecular evidence
should also be more similar in DNA and protein sequences than are more distantly related
 In fact, that is so.
Biology Chapter Notes
 For example, if we compare the sequence of 146 amino acids in a hemoglobin
polypeptide, we find that humans and gorillas differ in just 1 amino acid.
 Humans and gibbons differ in 2 amino acids.
 Humans and rhesus monkeys differ in 8 amino acids.
 More distantly related species have more differences.
 Humans and mice differ in 27 amino acids.
 Humans and frogs differ in 67 amino acids.
 Molecular biology can be used to assess evolutionary kinship.

Biology Chapter Notes

Chapter 6 A Tour of the Cell
Chapter Notes

Overview: The Importance of Cells

 All organisms are made of cells.

 Many organisms are single-celled.
 Even in multicellular organisms, the cell is the basic unit of structure and function.
 The cell is the simplest collection of matter that can live.
 All cells are related by their descent from earlier cells.

Concept 6.1 To study cells, biologists use microscopes and the tools of biochemistry
 The discovery and early study of cells progressed with the invention of microscopes in
1590 and their improvement in the 17th century.
 In a light microscope (LM), visible light passes through the specimen and then through
glass lenses.
 The lenses refract light such that the image is magnified into the eye or onto a video
 Microscopes vary in magnification and resolving power.
 Magnification is the ratio of an object’s image to its real size.
 Resolving power is a measure of image clarity.
 It is the minimum distance two points can be separated and still be distinguished as
two separate points.
 Resolution is limited by the shortest wavelength of the radiation used for imaging.
 The minimum resolution of a light microscope is about 200 nanometers (nm), the size of a
small bacterium.
 Light microscopes can magnify effectively to about 1,000 times the size of the actual
 At higher magnifications, the image blurs.
 Techniques developed in the 20th century have enhanced contrast and enabled particular
cell components to be stained or labeled so they stand out.
 While a light microscope can resolve individual cells, it cannot resolve much of the
internal anatomy, especially the organelles.
 To resolve smaller structures, we use an electron microscope (EM), which focuses a
beam of electrons through the specimen or onto its surface.
 Because resolution is inversely related to wavelength used, electron microscopes
(whose electron beams have shorter wavelengths than visible light) have finer
 Theoretically, the resolution of a modern EM could reach 0.002 nanometer (nm), but
the practical limit is closer to about 2 nm.
 Transmission electron microscopes (TEMs) are used mainly to study the internal
ultrastructure of cells.
Biology Chapter Notes
 A TEM aims an electron beam through a thin section of the specimen.
 The image is focused and magnified by electromagnets.
 To enhance contrast, the thin sections are stained with atoms of heavy metals.
 Scanning electron microscopes (SEMs) are useful for studying surface structures.
 The sample surface is covered with a thin film of gold.
 The beam excites electrons on the surface of the sample.
 These secondary electrons are collected and focused on a screen.
 The result is an image of the topography of the specimen.
 The SEM has great depth of field, resulting in an image that seems three-dimensional.
 Electron microscopes reveal organelles that are impossible to resolve with the light
 However, electron microscopes can only be used on dead cells.
 Light microscopes do not have as high a resolution, but they can be used to study live
 Microscopes are major tools in cytology, the study of cell structures.
 Cytology combined with biochemistry, the study of molecules and chemical processes in
metabolism, to produce modern cell biology.
Cell biologists can isolate organelles to study their functions.
 The goal of cell fractionation is to separate the major organelles of the cells so their
individual functions can be studied.
 This process is driven by an ultracentrifuge, a machine that can spin at up to 130,000
revolutions per minute and apply forces of more than 1 million times gravity (1,000,000
 Fractionation begins with homogenization, gently disrupting the cell.
 The homogenate is spun in a centrifuge to separate heavier pieces into the pellet while
lighter particles remain in the supernatant.
 As the process is repeated at higher speeds and for longer durations, smaller and
smaller organelles can be collected in subsequent pellets.
 Cell fractionation prepares isolates of specific cell components.
 This enables the functions of these organelles to be determined, especially by the
reactions or processes catalyzed by their proteins.
 For example, one cellular fraction was enriched in enzymes that function in cellular
 Electron microscopy revealed that this fraction is rich in mitochondria.
 This evidence helped cell biologists determine that mitochondria are the site of cellular
 Cytology and biochemistry complement each other in correlating cellular structure and

Concept 6.2 Eukaryotic cells have internal membranes that compartmentalize their
Prokaryotic and eukaryotic cells differ in size and complexity.
Biology Chapter Notes
 All cells are surrounded by a plasma membrane.
 The semifluid substance within the membrane is the cytosol, containing the organelles.
 All cells contain chromosomes that have genes in the form of DNA.
 All cells also have ribosomes, tiny organelles that make proteins using the instructions
contained in genes.
 A major difference between prokaryotic and eukaryotic cells is the location of
 In a eukaryotic cell, chromosomes are contained in a membrane-enclosed organelle, the
 In a prokaryotic cell, the DNA is concentrated in the nucleoid without a membrane
separating it from the rest of the cell.
 In eukaryote cells, the chromosomes are contained within a membranous nuclear
 The region between the nucleus and the plasma membrane is the cytoplasm.
 All the material within the plasma membrane of a prokaryotic cell is cytoplasm.
 Within the cytoplasm of a eukaryotic cell are a variety of membrane-bound organelles of
specialized form and function.
 These membrane-bound organelles are absent in prokaryotes.
 Eukaryotic cells are generally much bigger than prokaryotic cells.
 The logistics of carrying out metabolism set limits on cell size.
 At the lower limit, the smallest bacteria, mycoplasmas, are between 0.1 to 1.0 micron.
 Most bacteria are 1–10 microns in diameter.
 Eukaryotic cells are typically 10–100 microns in diameter.
 Metabolic requirements also set an upper limit to the size of a single cell.
 As a cell increases in size, its volume increases faster than its surface area.
 Smaller objects have a greater ratio of surface area to volume.
 The plasma membrane functions as a selective barrier that allows the passage of oxygen,
nutrients, and wastes for the whole volume of the cell.
 The volume of cytoplasm determines the need for this exchange.
 Rates of chemical exchange across the plasma membrane may be inadequate to maintain a
cell with a very large cytoplasm.
 The need for a surface sufficiently large to accommodate the volume explains the
microscopic size of most cells.
 Larger organisms do not generally have larger cells than smaller organisms—simply
more cells.
 Cells that exchange a lot of material with their surroundings, such as intestinal cells, may
have long, thin projections from the cell surface called microvilli. Microvilli increase
surface area without significantly increasing cell volume.
Internal membranes compartmentalize the functions of a eukaryotic cell.
 A eukaryotic cell has extensive and elaborate internal membranes, which partition the cell
into compartments.

Biology Chapter Notes

 These membranes also participate directly in metabolism, as many enzymes are built into
 The compartments created by membranes provide different local environments that
facilitate specific metabolic functions, allowing several incompatible processes to go on
simultaneously in a cell.
 The general structure of a biological membrane is a double layer of phospholipids.
 Other lipids and diverse proteins are embedded in the lipid bilayer or attached to its
 Each type of membrane has a unique combination of lipids and proteins for its specific
 For example, enzymes embedded in the membranes of mitochondria function in
cellular respiration.

Concept 6.3 The eukaryotic cell’s genetic instructions are housed in the nucleus and
carried out by the ribosomes
 The nucleus contains most of the genes in a eukaryotic cell.
 Additional genes are located in mitochondria and chloroplasts.
 The nucleus averages about 5 microns in diameter.
 The nucleus is separated from the cytoplasm by a double membrane called the nuclear
 The two membranes of the nuclear envelope are separated by 20–40 nm.
 The envelope is perforated by pores that are about 100 nm in diameter.
 At the lip of each pore, the inner and outer membranes of the nuclear envelope are
fused to form a continuous membrane.
 A protein structure called a pore complex lines each pore, regulating the passage of
certain large macromolecules and particles.
 The nuclear side of the envelope is lined by the nuclear lamina, a network of protein
filaments that maintains the shape of the nucleus.
 There is evidence that a framework of fibers called the nuclear matrix extends through
the nuclear interior.
 Within the nucleus, the DNA and associated proteins are organized into discrete units
called chromosomes, structures that carry the genetic information.
 Each chromosome is made up of fibrous material called chromatin, a complex of proteins
and DNA.
 Stained chromatin appears through light microscopes and electron microscopes as a
diffuse mass.
 As the cell prepares to divide, the chromatin fibers coil up and condense, becoming thick
enough to be recognized as the familiar chromosomes.
 Each eukaryotic species has a characteristic number of chromosomes.
 A typical human cell has 46 chromosomes.
 A human sex cell (egg or sperm) has only 23 chromosomes.
 In the nucleus is a region of densely stained fibers and granules adjoining chromatin, the
Biology Chapter Notes
 In the nucleolus, ribosomal RNA (rRNA) is synthesized and assembled with proteins
from the cytoplasm to form ribosomal subunits.
 The subunits pass through the nuclear pores to the cytoplasm, where they combine to
form ribosomes.
 The nucleus directs protein synthesis by synthesizing messenger RNA (mRNA).
 The mRNA travels to the cytoplasm through the nuclear pores and combines with
ribosomes to translate its genetic message into the primary structure of a specific
Ribosomes build a cell’s proteins.
 Ribosomes, containing rRNA and protein, are the organelles that carry out protein
 Cell types that synthesize large quantities of proteins (e.g., pancreas cells) have large
numbers of ribosomes and prominent nucleoli.
 Some ribosomes, free ribosomes, are suspended in the cytosol and synthesize proteins that
function within the cytosol.
 Other ribosomes, bound ribosomes, are attached to the outside of the endoplasmic
reticulum or nuclear envelope.
 These synthesize proteins that are either included in membranes or exported from the
 Ribosomes can shift between roles depending on the polypeptides they are synthesizing.

Concept 6.4 The endomembrane system regulates protein traffic and performs
metabolic functions in the cell
 Many of the internal membranes in a eukaryotic cell are part of the endomembrane
 These membranes are either directly continuous or connected via transfer of vesicles, sacs
of membrane.
 In spite of these connections, these membranes are diverse in function and structure.
 The thickness, molecular composition and types of chemical reactions carried out by
proteins in a given membrane may be modified several times during a membrane’s
 The endomembrane system includes the nuclear envelope, endoplasmic reticulum, Golgi
apparatus, lysosomes, vacuoles, and the plasma membrane.
The endoplasmic reticulum manufactures membranes and performs many other
biosynthetic functions.
 The endoplasmic reticulum (ER) accounts for half the membranes in a eukaryotic cell.
 The ER includes membranous tubules and internal, fluid-filled spaces called cisternae.
 The ER membrane is continuous with the nuclear envelope, and the cisternal space of the
ER is continuous with the space between the two membranes of the nuclear envelope.
 There are two connected regions of ER that differ in structure and function.
 Smooth ER looks smooth because it lacks ribosomes.
 Rough ER looks rough because ribosomes (bound ribosomes) are attached to the
outside, including the outside of the nuclear envelope.
Biology Chapter Notes
 The smooth ER is rich in enzymes and plays a role in a variety of metabolic processes.
 Enzymes of smooth ER synthesize lipids, including oils, phospholipids, and steroids.
 These include the sex hormones of vertebrates and adrenal steroids.
 In the smooth ER of the liver, enzymes help detoxify poisons and drugs such as
alcohol and barbiturates.
 Frequent use of these drugs leads to the proliferation of smooth ER in liver cells,
increasing the rate of detoxification.
 This increases tolerance to the target and other drugs, so higher doses are required
to achieve the same effect.
 Smooth ER stores calcium ions.
 Muscle cells have a specialized smooth ER that pumps calcium ions from the
cytosol and stores them in its cisternal space.
 When a nerve impulse stimulates a muscle cell, calcium ions rush from the ER into
the cytosol, triggering contraction.
 Enzymes then pump the calcium back, readying the cell for the next stimulation.
 Rough ER is especially abundant in cells that secrete proteins.
 As a polypeptide is synthesized on a ribosome attached to rough ER, it is threaded into
the cisternal space through a pore formed by a protein complex in the ER membrane.
 As it enters the cisternal space, the new protein folds into its native conformation.
 Most secretory polypeptides are glycoproteins, proteins to which a carbohydrate is
 Secretory proteins are packaged in transport vesicles that carry them to their next
 Rough ER is also a membrane factory.
 Membrane-bound proteins are synthesized directly into the membrane.
 Enzymes in the rough ER also synthesize phospholipids from precursors in the cytosol.
 As the ER membrane expands, membrane can be transferred as transport vesicles to
other components of the endomembrane system.
The Golgi apparatus is the shipping and receiving center for cell products.
 Many transport vesicles from the ER travel to the Golgi apparatus for modification of
their contents.
 The Golgi is a center of manufacturing, warehousing, sorting, and shipping.
 The Golgi apparatus is especially extensive in cells specialized for secretion.
 The Golgi apparatus consists of flattened membranous sacs—cisternae—looking like a
stack of pita bread.
 The membrane of each cisterna separates its internal space from the cytosol.
 One side of the Golgi, the cis side, is located near the ER. The cis face receives
material by fusing with transport vesicles from the ER.
 The other side, the trans side, buds off vesicles that travel to other sites.
 During their transit from the cis to the trans side, products from the ER are usually
 The Golgi can also manufacture its own macromolecules, including pectin and other
noncellulose polysaccharides.
 The Golgi apparatus is a very dynamic structure.
Biology Chapter Notes
 According to the cisternal maturation model, the cisternae of the Golgi progress from
the cis to the trans face, carrying and modifying their protein cargo as they move.
 Finally, the Golgi sorts and packages materials into transport vesicles.
 Molecular identification tags are added to products to aid in sorting.
 Products are tagged with identifiers such as phosphate groups. These act like ZIP
codes on mailing labels to identify the product’s final destination.
Lysosomes are digestive compartments.
 A lysosome is a membrane-bound sac of hydrolytic enzymes that an animal cell uses to
digest macromolecules.
 Lysosomal enzymes can hydrolyze proteins, fats, polysaccharides, and nucleic acids.
 These enzymes work best at pH 5.
 Proteins in the lysosomal membrane pump hydrogen ions from the cytosol into the
lumen of the lysosomes.
 Rupture of one or a few lysosomes has little impact on a cell because the lysosomal
enzymes are not very active at the neutral pH of the cytosol.
 However, massive rupture of many lysosomes can destroy a cell by autodigestion.
 Lysosomal enzymes and membrane are synthesized by rough ER and then transferred to
the Golgi apparatus for further modification.
 Proteins on the inner surface of the lysosomal membrane are spared by digestion by their
three-dimensional conformations, which protect vulnerable bonds from hydrolysis.
 Lysosomes carry out intracellular digestion in a variety of circumstances.
 Amoebas eat by engulfing smaller organisms by phagocytosis.
 The food vacuole formed by phagocytosis fuses with a lysosome, whose enzymes
digest the food.
 As the polymers are digested, monomers pass to the cytosol to become nutrients for the
 Lysosomes can play a role in recycling of the cell’s organelles and macromolecules.
 This recycling, or autophagy, renews the cell.
 During autophagy, a damaged organelle or region of cytosol becomes surrounded by
 A lysosome fuses with the resulting vesicle, digesting the macromolecules and
returning the organic monomers to the cytosol for reuse.
 The lysosomes play a critical role in the programmed destruction of cells in multicellular
 This process plays an important role in development.
 The hands of human embryos are webbed until lysosomes digest the cells in the tissue
between the fingers.
 This important process is called programmed cell death, or apoptosis.
Vacuoles have diverse functions in cell maintenance.
 Vesicles and vacuoles (larger versions) are membrane-bound sacs with varied functions.
 Food vacuoles are formed by phagocytosis and fuse with lysosomes.
 Contractile vacuoles, found in freshwater protists, pump excess water out of the cell
to maintain the appropriate concentration of salts.
 A large central vacuole is found in many mature plant cells.
Biology Chapter Notes
 The membrane surrounding the central vacuole, the tonoplast, is selective in its
transport of solutes into the central vacuole.
 The functions of the central vacuole include stockpiling proteins or inorganic ions,
disposing of metabolic byproducts, holding pigments, and storing defensive
compounds that defend the plant against herbivores.
 Because of the large vacuole, the cytosol occupies only a thin layer between the
plasma membrane and the tonoplast. The presence of a large vacuole increases
surface area to volume ratio for the cell.

Concept 6.5 Mitochondria and chloroplasts change energy from one form to another
 Mitochondria and chloroplasts are the organelles that convert energy to forms that cells
can use for work.
 Mitochondria are the sites of cellular respiration, generating ATP from the catabolism of
sugars, fats, and other fuels in the presence of oxygen.
 Chloroplasts, found in plants and algae, are the sites of photosynthesis.
 They convert solar energy to chemical energy and synthesize new organic compounds
such as sugars from CO2 and H2O.
 Mitochondria and chloroplasts are not part of the endomembrane system.
 In contrast to organelles of the endomembrane system, each mitochondrion or
chloroplast has two membranes separating the innermost space from the cytosol.
 Their membrane proteins are not made by the ER, but rather by free ribosomes in the
cytosol and by ribosomes within the organelles themselves.
 Both organelles have small quantities of DNA that direct the synthesis of the polypeptides
produced by these internal ribosomes.
 Mitochondria and chloroplasts grow and reproduce as semiautonomous organelles.
 Almost all eukaryotic cells have mitochondria.
 There may be one very large mitochondrion or hundreds to thousands of individual
 The number of mitochondria is correlated with aerobic metabolic activity.
 A typical mitochondrion is 1–10 microns long.
 Mitochondria are quite dynamic: moving, changing shape, and dividing.
 Mitochondria have a smooth outer membrane and a convoluted inner membrane with
infoldings called cristae.
 The inner membrane divides the mitochondrion into two internal compartments.
 The first is the intermembrane space, a narrow region between the inner and outer
 The inner membrane encloses the mitochondrial matrix, a fluid-filled space with
DNA, ribosomes, and enzymes.
 Some of the metabolic steps of cellular respiration are catalyzed by enzymes in the
 The cristae present a large surface area for the enzymes that synthesize ATP.
 The chloroplast is one of several members of a generalized class of plant structures called
 Amyloplasts are colorless plastids that store starch in roots and tubers.
 Chromoplasts store pigments for fruits and flowers.
Biology Chapter Notes
 Chloroplasts contain the green pigment chlorophyll as well as enzymes and other
molecules that function in the photosynthetic production of sugar.
 Chloroplasts measure about 2 microns × 5 microns and are found in leaves and other
green organs of plants and algae.
 The contents of the chloroplast are separated from the cytosol by an envelope consisting
of two membranes separated by a narrow intermembrane space.
 Inside the innermost membrane is a fluid-filled space, the stroma, in which float
membranous sacs, the thylakoids.
 The stroma contains DNA, ribosomes, and enzymes.
 The thylakoids are flattened sacs that play a critical role in converting light to chemical
energy. In some regions, thylakoids are stacked like poker chips into grana.
 The membranes of the chloroplast divide the chloroplast into three compartments: the
intermembrane space, the stroma, and the thylakoid space.
 Like mitochondria, chloroplasts are dynamic structures.
 Their shape is plastic, and they can reproduce themselves by pinching in two.
 Mitochondria and chloroplasts are mobile and move around the cell along tracks of the
Peroxisomes generate and degrade H2O2 in performing various metabolic functions.
 Peroxisomes contain enzymes that transfer hydrogen from various substrates to oxygen.
 An intermediate product of this process is hydrogen peroxide (H2O2), a poison.
 The peroxisome contains an enzyme that converts H2O2 to water.
 Some peroxisomes break fatty acids down to smaller molecules that are transported to
mitochondria as fuel for cellular respiration.
 Peroxisomes in the liver detoxify alcohol and other harmful compounds.
 Specialized peroxisomes, glyoxysomes, convert the fatty acids in seeds to sugars,
which the seedling can use as a source of energy and carbon until it is capable of
 Peroxisomes are bound by a single membrane.
 They form not from the endomembrane system, but by incorporation of proteins and
lipids from the cytosol.
 They split in two when they reach a certain size.

Concept 6.6 The cytoskeleton is a network of fibers that organizes structures and
activities in the cell
 The cytoskeleton is a network of fibers extending throughout the cytoplasm.
 The cytoskeleton organizes the structures and activities of the cell.
The cytoskeleton provides support, motility, and regulation.
 The cytoskeleton provides mechanical support and maintains cell shape.
 The cytoskeleton provides anchorage for many organelles and cytosolic enzymes.
 The cytoskeleton is dynamic and can be dismantled in one part and reassembled in
another to change the shape of the cell.

Biology Chapter Notes

 The cytoskeleton also plays a major role in cell motility, including changes in cell location
and limited movements of parts of the cell.
 The cytoskeleton interacts with motor proteins to produce motility.
 Cytoskeleton elements and motor proteins work together with plasma membrane
molecules to move the whole cell along fibers outside the cell.
 Motor proteins bring about movements of cilia and flagella by gripping cytoskeletal
components such as microtubules and moving them past each other.
 The same mechanism causes muscle cells to contract.
 Inside the cell, vesicles can travel along “monorails” provided by the cytoskeleton.
 The cytoskeleton manipulates the plasma membrane to form food vacuoles during
 Cytoplasmic streaming in plant cells is caused by the cytoskeleton.
 Recently, evidence suggests that the cytoskeleton may play a role in the regulation of
biochemical activities in the cell.
 There are three main types of fibers making up the cytoskeleton: microtubules,
microfilaments, and intermediate filaments.
 Microtubules, the thickest fibers, are hollow rods about 25 microns in diameter and 200
nm to 25 microns in length.
 Microtubule fibers are constructed of the globular protein tubulin.
 Each tubulin molecule is a dimer consisting of two subunits.
 A microtubule changes in length by adding or removing tubulin dimers.
 Microtubules shape and support the cell and serve as tracks to guide motor proteins
carrying organelles to their destination.
 Microtubules are also responsible for the separation of chromosomes during cell division.
 In many cells, microtubules grow out from a centrosome near the nucleus.
 These microtubules resist compression to the cell.
 In animal cells, the centrosome has a pair of centrioles, each with nine triplets of
microtubules arranged in a ring.
 Before a cell divides, the centrioles replicate.
 A specialized arrangement of microtubules is responsible for the beating of cilia and
 Many unicellular eukaryotic organisms are propelled through water by cilia and
 Cilia or flagella can extend from cells within a tissue layer, beating to move fluid over
the surface of the tissue.
 For example, cilia lining the windpipe sweep mucus carrying trapped debris out of
the lungs.
 Cilia usually occur in large numbers on the cell surface.
 They are about 0.25 microns in diameter and 2–20 microns long.
 There are usually just one or a few flagella per cell.
 Flagella are the same width as cilia, but 10–200 microns long.
 Cilia and flagella differ in their beating patterns.
 A flagellum has an undulatory movement that generates force in the same direction as
the flagellum’s axis.
Biology Chapter Notes
 Cilia move more like oars with alternating power and recovery strokes that generate
force perpendicular to the cilium’s axis.
 In spite of their differences, both cilia and flagella have the same ultrastructure.
 Both have a core of microtubules sheathed by the plasma membrane.
 Nine doublets of microtubules are arranged in a ring around a pair at the center. This
“9 + 2” pattern is found in nearly all eukaryotic cilia and flagella.
 Flexible “wheels” of proteins connect outer doublets to each other and to the two
central microtubules.
 The outer doublets are also connected by motor proteins.
 The cilium or flagellum is anchored in the cell by a basal body, whose structure is
identical to a centriole.
 The bending of cilia and flagella is driven by the arms of a motor protein, dynein.
 Addition and removal of a phosphate group causes conformation changes in dynein.
 Dynein arms alternately grab, move, and release the outer microtubules.
 Protein cross-links limit sliding. As a result, the forces exerted by the dynein arms
cause the doublets to curve, bending the cilium or flagellum.
 Microfilaments are solid rods about 7 nm in diameter.
 Each microfilament is built as a twisted double chain of actin subunits.
 Microfilaments can form structural networks due to their ability to branch.
 The structural role of microfilaments in the cytoskeleton is to bear tension, resisting
pulling forces within the cell.
 They form a three-dimensional network just inside the plasma membrane to help support
the cell’s shape, giving the cell cortex the semisolid consistency of a gel.
 Microfilaments are important in cell motility, especially as part of the contractile
apparatus of muscle cells.
 In muscle cells, thousands of actin filaments are arranged parallel to one another.
 Thicker filaments composed of myosin interdigitate with the thinner actin fibers.
 Myosin molecules act as motor proteins, walking along the actin filaments to shorten
the cell.
 In other cells, actin-myosin aggregates are less organized but still cause localized
 A contracting belt of microfilaments divides the cytoplasm of animal cells during cell
 Localized contraction brought about by actin and myosin also drives amoeboid
 Pseudopodia, cellular extensions, extend and contract through the reversible
assembly and contraction of actin subunits into microfilaments.
 Microfilaments assemble into networks that convert sol to gel.
 According to a widely accepted model, filaments near the cell’s trailing edge
interact with myosin, causing contraction.
 The contraction forces the interior fluid into the pseudopodium, where the actin
network has been weakened.
 The pseudopodium extends until the actin reassembles into a network.

 In plant cells, actin-myosin interactions and sol-gel transformations drive cytoplasmic

Biology Chapter Notes
 This creates a circular flow of cytoplasm in the cell, speeding the distribution of
materials within the cell.
 Intermediate filaments range in diameter from 8–12 nanometers, larger than
microfilaments but smaller than microtubules.
 Intermediate filaments are a diverse class of cytoskeletal units, built from a family of
proteins called keratins.
 Intermediate filaments are specialized for bearing tension.
 Intermediate filaments are more permanent fixtures of the cytoskeleton than are the other
two classes.
 They reinforce cell shape and fix organelle location.

Concept 6.7 Extracellular components and connections between cells help coordinate
cellular activities
Plant cells are encased by cell walls.
 The cell wall, found in prokaryotes, fungi, and some protists, has multiple functions.
 In plants, the cell wall protects the cell, maintains its shape, and prevents excessive uptake
of water.
 It also supports the plant against the force of gravity.
 The thickness and chemical composition of cell walls differs from species to species and
among cell types within a plant.
 The basic design consists of microfibrils of cellulose embedded in a matrix of proteins
and other polysaccharides. This is the basic design of steel-reinforced concrete or
 A mature cell wall consists of a primary cell wall, a middle lamella with sticky
polysaccharides that holds cells together, and layers of secondary cell wall.
 Plant cell walls are perforated by channels between adjacent cells called plasmodesmata.
The extracellular matrix (ECM) of animal cells functions in support, adhesion,
movement, and regulation.
 Though lacking cell walls, animal cells do have an elaborate extracellular matrix
 The primary constituents of the extracellular matrix are glycoproteins, especially collagen
fibers, embedded in a network of glycoprotein proteoglycans.
 In many cells, fibronectins in the ECM connect to integrins, intrinsic membrane proteins
that span the membrane and bind on their cytoplasmic side to proteins attached to
microfilaments of the cytoskeleton.
 The interconnections from the ECM to the cytoskeleton via the fibronectin-integrin
link permit the integration of changes inside and outside the cell.
 The ECM can regulate cell behavior.
 Embryonic cells migrate along specific pathways by matching the orientation of their
microfilaments to the “grain” of fibers in the extracellular matrix.
 The extracellular matrix can influence the activity of genes in the nucleus via a
combination of chemical and mechanical signaling pathways.
Biology Chapter Notes
 This may coordinate the behavior of all the cells within a tissue.
Intercellular junctions help integrate cells into higher levels of structure and function.
 Neighboring cells in tissues, organs, or organ systems often adhere, interact, and
communicate through direct physical contact.
 Plant cells are perforated with plasmodesmata, channels allowing cytosol to pass
between cells.
 Water and small solutes can pass freely from cell to cell.
 In certain circumstances, proteins and RNA can be exchanged.
 Animals have 3 main types of intercellular links: tight junctions, desmosomes, and gap
 In tight junctions, membranes of adjacent cells are fused, forming continuous belts
around cells.
 This prevents leakage of extracellular fluid.
 Desmosomes (or anchoring junctions) fasten cells together into strong sheets, much like
 Intermediate filaments of keratin reinforce desmosomes.
 Gap junctions (or communicating junctions) provide cytoplasmic channels between
adjacent cells.
 Special membrane proteins surround these pores.
 Ions, sugars, amino acids, and other small molecules can pass.
 In embryos, gap junctions facilitate chemical communication during development.
A cell is a living unit greater than the sum of its parts.
 While the cell has many structures with specific functions, all these structures must work
 For example, macrophages use actin filaments to move and extend pseudopodia to
capture their bacterial prey.
 Food vacuoles are digested by lysosomes, a product of the endomembrane system of
ER and Golgi.
 The enzymes of the lysosomes and proteins of the cytoskeleton are synthesized on the
 The information for the proteins comes from genetic messages sent by DNA in the
 All of these processes require energy in the form of ATP, most of which is supplied by the
 A cell is a living unit greater than the sum of its parts.

Biology Chapter Notes

Chapter 7 Membrane Structure and Function
Chapter Notes

Overview: Life at the Edge

 The plasma membrane separates the living cell from its nonliving surroundings.
 This thin barrier, 8 nm thick, controls traffic into and out of the cell.
 Like all biological membranes, the plasma membrane is selectively permeable, allowing
some substances to cross more easily than others.

Concept 7.1 Cellular membranes are fluid mosaics of lipids and proteins
 The main macromolecules in membranes are lipids and proteins, but carbohydrates are
also important.
 The most abundant lipids are phospholipids.
 Phospholipids and most other membrane constituents are amphipathic molecules.
 Amphipathic molecules have both hydrophobic regions and hydrophilic regions.
 The arrangement of phospholipids and proteins in biological membranes is described by
the fluid mosaic model.
Membrane models have evolved to fit new data.
 Models of membranes were developed long before membranes were first seen with
electron microscopes in the 1950s.
 In 1915, membranes isolated from red blood cells were chemically analyzed and found
to be composed of lipids and proteins.
 In 1925, E. Gorter and F. Grendel reasoned that cell membranes must be a
phospholipid bilayer two molecules thick.
 The molecules in the bilayer are arranged such that the hydrophobic fatty acid tails are
sheltered from water while the hydrophilic phosphate groups interact with water.
 Actual membranes adhere more strongly to water than do artificial membranes
composed only of phospholipids.
 One suggestion was that proteins on the surface of the membrane increased adhesion.
 In 1935, H. Davson and J. Danielli proposed a sandwich model in which the
phospholipid bilayer lies between two layers of globular proteins.
 Early images from electron microscopes seemed to support the Davson-Danielli
model, and until the 1960s, it was widely accepted as the structure of the plasma
membrane and internal membranes.
 Further investigation revealed two problems.
 First, not all membranes were alike. Membranes differ in thickness, appearance
when stained, and percentage of proteins.
 Membranes with different functions differ in chemical composition and
 Second, measurements showed that membrane proteins are not very soluble in
Biology Chapter Notes
 Membrane proteins are amphipathic, with hydrophobic and hydrophilic regions.
 If membrane proteins were at the membrane surface, their hydrophobic regions
would be in contact with water.
 In 1972, S. J. Singer and G. Nicolson presented a revised model that proposed that the
membrane proteins are dispersed and individually inserted into the phospholipid bilayer.
 In this fluid mosaic model, the hydrophilic regions of proteins and phospholipids are in
maximum contact with water, and the hydrophobic regions are in a nonaqueous
environment within the membrane.
 A specialized preparation technique, freeze-fracture, splits a membrane along the middle
of the phospholipid bilayer.
 When a freeze-fracture preparation is viewed with an electron microscope, protein
particles are interspersed in a smooth matrix, supporting the fluid mosaic model.
Membranes are fluid.
 Membrane molecules are held in place by relatively weak hydrophobic interactions.
 Most of the lipids and some proteins drift laterally in the plane of the membrane, but
rarely flip-flop from one phospholipid layer to the other.
 The lateral movements of phospholipids are rapid, about 2 microns per second. A
phospholipid can travel the length of a typical bacterial cell in 1 second.
 Many larger membrane proteins drift within the phospholipid bilayer, although they move
more slowly than the phospholipids.
 Some proteins move in a very directed manner, perhaps guided or driven by motor
proteins attached to the cytoskeleton.
 Other proteins never move and are anchored to the cytoskeleton.
 Membrane fluidity is influenced by temperature. As temperatures cool, membranes switch
from a fluid state to a solid state as the phospholipids pack more closely.
 Membrane fluidity is also influenced by its components. Membranes rich in unsaturated
fatty acids are more fluid that those dominated by saturated fatty acids because the kinks
in the unsaturated fatty acid tails at the locations of the double bonds prevent tight
 The steroid cholesterol is wedged between phospholipid molecules in the plasma
membrane of animal cells.
 At warm temperatures (such as 37°C), cholesterol restrains the movement of
phospholipids and reduces fluidity.
 At cool temperatures, it maintains fluidity by preventing tight packing.
 Thus, cholesterol acts as a “temperature buffer” for the membrane, resisting changes in
membrane fluidity as temperature changes.
 To work properly with active enzymes and appropriate permeability, membranes must be
about as fluid as salad oil.
 Cells can alter the lipid composition of membranes to compensate for changes in fluidity
caused by changing temperatures.
 For example, cold-adapted organisms such as winter wheat increase the percentage of
unsaturated phospholipids in their membranes in the autumn.
 This prevents membranes from solidifying during winter.
Membranes are mosaics of structure and function.
Biology Chapter Notes
 A membrane is a collage of different proteins embedded in the fluid matrix of the lipid
 Proteins determine most of the membrane’s specific functions.
 The plasma membrane and the membranes of the various organelles each have unique
collections of proteins.
 There are two major populations of membrane proteins.
 Peripheral proteins are not embedded in the lipid bilayer at all.
 Instead, they are loosely bound to the surface of the protein, often connected to
integral proteins.
 Integral proteins penetrate the hydrophobic core of the lipid bilayer, often completely
spanning the membrane (as transmembrane proteins).
 The hydrophobic regions embedded in the membrane’s core consist of stretches of
nonpolar amino acids, often coiled into alpha helices.
 Where integral proteins are in contact with the aqueous environment, they have
hydrophilic regions of amino acids.
 On the cytoplasmic side of the membrane, some membrane proteins connect to the
 On the exterior side of the membrane, some membrane proteins attach to the fibers of
the extracellular matrix.
 The proteins of the plasma membrane have six major functions:
4. Transport of specific solutes into or out of cells.
5. Enzymatic activity, sometimes catalyzing one of a number of steps of a metabolic
6. Signal transduction, relaying hormonal messages to the cell.
7. Cell-cell recognition, allowing other proteins to attach two adjacent cells together.
8. Intercellular joining of adjacent cells with gap or tight junctions.
9. Attachment to the cytoskeleton and extracellular matrix, maintaining cell shape
and stabilizing the location of certain membrane proteins.
Membrane carbohydrates are important for cell-cell recognition.
 The plasma membrane plays the key role in cell-cell recognition.
 Cell-cell recognition, the ability of a cell to distinguish one type of neighboring cell
from another, is crucial to the functioning of an organism.
 This attribute is important in the sorting and organization of cells into tissues and
organs during development.
 It is also the basis for rejection of foreign cells by the immune system.
 Cells recognize other cells by binding to surface molecules, often carbohydrates, on
the plasma membrane.
 Membrane carbohydrates are usually branched oligosaccharides with fewer than 15 sugar
 They may be covalently bonded to lipids, forming glycolipids, or more commonly to
proteins, forming glycoproteins.
 The oligosaccharides on the external side of the plasma membrane vary from species to
species, from individual to individual, and even from cell type to cell type within the same
 This variation distinguishes each cell type.
Biology Chapter Notes
 The four human blood groups (A, B, AB, and O) differ in the external carbohydrates
on red blood cells.
Membranes have distinctive inside and outside faces.
 Membranes have distinct inside and outside faces. The two layers may differ in lipid
composition. Each protein in the membrane has a directional orientation in the membrane.
 The asymmetrical orientation of proteins, lipids and associated carbohydrates begins
during the synthesis of membrane in the ER and Golgi apparatus.
 Membrane lipids and proteins are synthesized in the endoplasmic reticulum.
Carbohydrates are added to proteins in the ER, and the resulting glycoproteins are further
modified in the Golgi apparatus. Glycolipids are also produced in the Golgi apparatus.
 When a vesicle fuses with the plasma membrane, the outside layer of the vesicle becomes
continuous with the inside layer of the plasma membrane. In that way, molecules that
originate on the inside face of the ER end up on the outside face of the plasma membrane.

Concept 7.2 Membrane structure results in selective permeability

 A steady traffic of small molecules and ions moves across the plasma membrane in both
 For example, sugars, amino acids, and other nutrients enter a muscle cell, and
metabolic waste products leave.
 The cell absorbs oxygen and expels carbon dioxide.
 It also regulates concentrations of inorganic ions, such as Na +, K+, Ca2+, and Cl−, by
shuttling them across the membrane.
 However, substances do not move across the barrier indiscriminately; membranes are
selectively permeable.
 The plasma membrane allows the cell to take up many varieties of small molecules and
ions and exclude others. Substances that move through the membrane do so at different
 Movement of a molecule through a membrane depends on the interaction of the molecule
with the hydrophobic core of the membrane.
 Hydrophobic molecules, such as hydrocarbons, CO 2, and O2, can dissolve in the lipid
bilayer and cross easily.
 The hydrophobic core of the membrane impedes the direct passage of ions and polar
molecules, which cross the membrane with difficulty.
 This includes small molecules, such as water, and larger molecules, such as glucose
and other sugars.
 An ion, whether a charged atom or molecule, and its surrounding shell of water also
has difficulty penetrating the hydrophobic core.
 Proteins assist and regulate the transport of ions and polar molecules.
 Specific ions and polar molecules can cross the lipid bilayer by passing through transport
proteins that span the membrane.
 Some transport proteins, called channel proteins, have a hydrophilic channel that
certain molecules or ions can use as a tunnel through the membrane.
 For example, the passage of water through the membrane can be greatly facilitated by
channel proteins known as aquaporins.

Biology Chapter Notes

 Other transport proteins, called carrier proteins, bind to molecules and change shape
to shuttle them across the membrane.
 Each transport protein is specific as to the substances that it will translocate.
 For example, the glucose transport protein in the liver will carry glucose into the cell
but will not transport fructose, its structural isomer.

Concept 7.3 Passive transport is diffusion of a substance across a membrane with no

energy investment
 Diffusion is the tendency of molecules of any substance to spread out in the available
 Diffusion is driven by the intrinsic kinetic energy (thermal motion or heat) of
 Movements of individual molecules are random.
 However, movement of a population of molecules may be directional.
 Imagine a permeable membrane separating a solution with dye molecules from pure
water. If the membrane has microscopic pores that are large enough, dye molecules will
cross the barrier randomly.
 The net movement of dye molecules across the membrane will continue until both sides
have equal concentrations of the dye.
 At this dynamic equilibrium, as many molecules cross one way as cross in the other
 In the absence of other forces, a substance will diffuse from where it is more concentrated
to where it is less concentrated, down its concentration gradient.
 No work must be done to move substances down the concentration gradient.
 Diffusion is a spontaneous process that decreases free energy and increases entropy by
creating a randomized mixture.
 Each substance diffuses down its own concentration gradient, independent of the
concentration gradients of other substances.
 The diffusion of a substance across a biological membrane is passive transport because it
requires no energy from the cell to make it happen.
 The concentration gradient itself represents potential energy and drives diffusion.
 Because membranes are selectively permeable, the interactions of the molecules with the
membrane play a role in the diffusion rate.
 Diffusion of molecules of limited permeability through the lipid bilayer may be assisted
by transport proteins.
Osmosis is the passive transport of water.
 Differences in the relative concentration of dissolved materials in two solutions can lead
to the movement of ions from one to the other.
 The solution with the higher concentration of solutes is hypertonic relative to the other
 The solution with the lower concentration of solutes is hypotonic relative to the other
 These are comparative terms.
Biology Chapter Notes
 Tap water is hypertonic compared to distilled water but hypotonic compared to
 Solutions with equal solute concentrations are isotonic.
 Imagine that two sugar solutions differing in concentration are separated by a membrane
that will allow water through, but not sugar.
 The hypertonic solution has a lower water concentration than the hypotonic solution.
 More of the water molecules in the hypertonic solution are bound up in hydration
shells around the sugar molecules, leaving fewer unbound water molecules.
 Unbound water molecules will move from the hypotonic solution, where they are
abundant, to the hypertonic solution, where they are rarer. Net movement of water
continues until the solutions are isotonic.
 The diffusion of water across a selectively permeable membrane is called osmosis.
 The direction of osmosis is determined only by a difference in total solute concentration.
 The kinds of solutes in the solutions do not matter.
 This makes sense because the total solute concentration is an indicator of the
abundance of bound water molecules (and, therefore, of free water molecules).
 When two solutions are isotonic, water molecules move at equal rates from one to the
other, with no net osmosis.
 The movement of water by osmosis is crucial to living organisms.
Cell survival depends on balancing water uptake and loss.
 An animal cell (or other cell without a cell wall) immersed in an isotonic environment experiences no net
movement of water across its plasma membrane.
 Water molecules move across the membrane but at the same rate in both directions.
 The volume of the cell is stable.
 The same cell in a hypertonic environment will lose water, shrivel, and probably die.
 A cell in a hypotonic solution will gain water, swell, and burst.
 For organisms living in an isotonic environment (for example, many marine
invertebrates), osmosis is not a problem.
 The cells of most land animals are bathed in extracellular fluid that is isotonic to the
 Organisms without rigid walls have osmotic problems in either a hypertonic or hypotonic
environment and must have adaptations for osmoregulation, the control of water balance,
to maintain their internal environment.
 For example, Paramecium, a protist, is hypertonic to the pond water in which it lives.
 In spite of a cell membrane that is less permeable to water than other cells, water still
continually enters the Paramecium cell.
 To solve this problem, Paramecium cells have a specialized organelle, the contractile
vacuole, which functions as a bilge pump to force water out of the cell.
 The cells of plants, prokaryotes, fungi, and some protists have walls that contribute to the
cell’s water balance.
 A plant cell in a hypotonic solution will swell until the elastic cell wall opposes further
 At this point the cell is turgid (very firm), a healthy state for most plant cells.

Biology Chapter Notes

 Turgid cells contribute to the mechanical support of the plant.
 If a plant cell and its surroundings are isotonic, there is no movement of water into the
cell. The cell becomes flaccid (limp), and the plant may wilt.
 The cell wall provides no advantages when a plant cell is immersed in a hypertonic
solution. As the plant cell loses water, its volume shrinks. Eventually, the plasma
membrane pulls away from the wall. This plasmolysis is usually lethal.
Specific proteins facilitate passive transport of water and selected solutes.
 Many polar molecules and ions that are normally impeded by the lipid bilayer of the
membrane diffuse passively with the help of transport proteins that span the membrane.
 The passive movement of molecules down their concentration gradient via transport
proteins is called facilitated diffusion.
 Two types of transport proteins facilitate the movement of molecules or ions across
membranes: channel proteins and carrier proteins.
 Some channel proteins simply provide hydrophilic corridors for the passage of specific
molecules or ions.
 For example, water channel proteins, aquaporins, greatly facilitate the diffusion of
 Many ion channels function as gated channels. These channels open or close depending
on the presence or absence of a chemical or physical stimulus.
 If chemical, the stimulus is a substance other than the one to be transported.
 For example, stimulation of a receiving neuron by specific neurotransmitters opens
gated channels to allow sodium ions into the cell.
 When the neurotransmitters are not present, the channels are closed.
 Some transport proteins do not provide channels but appear to actually translocate the
solute-binding site and solute across the membrane as the transport protein changes shape.
 These shape changes may be triggered by the binding and release of the transported
 In certain inherited diseases, specific transport systems may be defective or absent.
 Cystinuria is a human disease characterized by the absence of a protein that transports
cysteine and other amino acids across the membranes of kidney cells.
 An individual with cystinuria develops painful kidney stones as amino acids
accumulate and crystallize in the kidneys.

Concept 7.4 Active transport uses energy to move solutes against their gradients
 Some transport proteins can move solutes across membranes against their concentration
gradient, from the side where they are less concentrated to the side where they are more
 This active transport requires the cell to expend metabolic energy.
 Active transport enables a cell to maintain its internal concentrations of small molecules
that would otherwise diffuse across the membrane.
 Active transport is performed by specific proteins embedded in the membranes.
 ATP supplies the energy for most active transport.

Biology Chapter Notes

 ATP can power active transport by transferring a phosphate group from ATP (forming
ADP) to the transport protein.
 This may induce a conformational change in the transport protein, translocating the
solute across the membrane.
 The sodium-potassium +
pump actively maintains the gradient of sodium ions (Na +) and
potassium ions (K ) across the plasma membrane of animal cells.
 Typically,+ K+ concentration is low outside an animal cell and high inside the cell,
while Na concentration is high outside an animal cell and low inside the cell.
 The sodium-potassium pump maintains these concentration gradients, using the energy
of one ATP to pump three Na+ out and two K+ in.
Some ion pumps generate voltage across membranes.
 All cells maintain a voltage across their plasma membranes.
 Voltage is electrical potential energy due to the separation of opposite charges.
 The cytoplasm of a cell is negative in charge compared to the extracellular fluid
because of an unequal distribution of cations and anions on opposite sides of the
 The voltage across a membrane is called a membrane potential, and ranges from −50
to −200 millivolts (mV). The inside of the cell is negative compared to the outside.
 The membrane potential acts like a battery.
 The membrane potential favors the passive transport of cations into the cell and anions out
of the cell.
 Two combined forces, collectively called the electrochemical gradient, drive the
diffusion of ions across a membrane.
 One is a chemical force based on an ion’s concentration gradient.
 The other is an electrical force based on the effect of the membrane potential on the
ion’s movement.
 An ion does not simply diffuse down its concentration gradient but diffuses down its
electrochemical gradient.
 For example, there is a higher concentration of Na + outside a resting nerve cell than
 When the neuron is stimulated, a gated channel opens and Na++ diffuse into the cell
down their electrochemical gradient. The diffusion of Na is driven by their
concentration gradient and by the attraction of cations to the negative side of the
 Special transport proteins, electrogenic pumps, generate the voltage gradient across a
 The sodium-potassium pump+in animals +
restores the electrochemical gradient not only
by the active transport of Na and K , setting up a concentration gradient, but because
it pumps two K+ inside for every three Na+ that it moves out, setting up a voltage
across the membrane.
 The sodium-potassium pump is the major electrogenic pump of animal cells.
 In plants, bacteria, and fungi, a proton pump is the major electrogenic pump, actively
transporting H+ out of the cell.
 Proton pumps in the cristae of mitochondria and the thylakoids of chloroplasts concentrate
H+ behind membranes.

Biology Chapter Notes

 These electrogenic pumps store energy that can be accessed for cellular work.
In cotransport, a membrane protein couples the transport of two solutes.
 A single ATP-powered pump that transports one solute can indirectly drive the active
transport of several other solutes in a mechanism called cotransport.
 As the solute that has been actively transported diffuses back passively through a transport
protein, its movement can be coupled with the active transport of another substance
against its concentration gradient.
 Plants commonly use the gradient of hydrogen ions generated by proton pumps to drive
the active transport of amino acids, sugars, and other nutrients into the cell.
 One specific transport protein couples the diffusion of protons out of the cell and the
transport of sucrose into the cell. Plants use the mechanism of sucrose-proton cotransport
to load sucrose into specialized cells in the veins of leaves for distribution to
nonphotosynthetic organs such as roots.

Concept 7.5 Bulk transport across the plasma membrane occurs by exocytosis and
 Small molecules and water enter or leave the cell through the lipid bilayer or by transport
 Large molecules, such as polysaccharides and proteins, cross the membrane via vesicles.
 During exocytosis, a transport vesicle budded from the Golgi apparatus is moved by the
cytoskeleton to the plasma membrane.
 When the two membranes come in contact, the bilayers fuse and spill the contents to the
 Many secretory cells use exocytosis to export their products.
 During endocytosis, a cell brings in macromolecules and particulate matter by forming
new vesicles from the plasma membrane.
 Endocytosis is a reversal of exocytosis, although different proteins are involved in the two
 A small area of the plasma membrane sinks inward to form a pocket.
 As the pocket deepens, it pinches in to form a vesicle containing the material that had
been outside the cell.
 There are three types of endocytosis: phagocytosis (“cellular eating”), pinocytosis
(“cellular drinking”), and receptor-mediated endocytosis.
 In phagocytosis, the cell engulfs a particle by extending pseudopodia around it and
packaging it in a large vacuole.
 The contents of the vacuole are digested when the vacuole fuses with a lysosome.
 In pinocytosis, a cell creates a vesicle around a droplet of extracellular fluid. All included
solutes are taken into the cell in this nonspecific process.
 Receptor-mediated endocytosis allows greater specificity, transporting only certain
 This process is triggered when extracellular substances, or ligands, bind to special
receptors on the membrane surface. The receptor proteins are clustered in regions of the

Biology Chapter Notes

membrane called coated pits, which are lined on their cytoplasmic side by a layer of coat
 Binding of ligands to receptors triggers the formation of a vesicle by the coated pit,
bringing the bound substances into the cell.
 Receptor-mediated endocytosis enables a cell to acquire bulk quantities of specific
materials that may be in low concentrations in the environment.
 Human cells use this process to take in cholesterol for use in the synthesis of
membranes and as a precursor for the synthesis of steroids.
 Cholesterol travels in the blood in low-density lipoproteins (LDL), complexes of
protein and lipid.
 These lipoproteins act as ligands to bind to LDL receptors and enter the cell by
 In an inherited disease called familial hypercholesterolemia, the LDL receptors are
defective, leading to an accumulation of LDL and cholesterol in the blood.
 This contributes to early atherosclerosis.

Biology Chapter Notes

Chapter 8 An Introduction to Metabolism
Chapter Notes

Overview: The Energy of Life

Concept 8.1 An organism’s metabolism transforms matter and energy, subject to the
laws of thermodynamics
 The totality of an organism’s chemical reactions is called metabolism.
 Metabolism is an emergent property of life that arises from interactions between
molecules within the orderly environment of the cell.
The chemistry of life is organized into metabolic pathways.
 Metabolic pathways begin with a specific molecule, which is then altered in a series of
defined steps to form a specific product.
 A specific enzyme catalyzes each step of the pathway.
 Catabolic pathways release energy by breaking down complex molecules to simpler
 A major pathway of catabolism is cellular respiration, in which the sugar glucose is
broken down in the presence of oxygen to carbon dioxide and water.
 Anabolic pathways consume energy to build complicated molecules from simpler
compounds. They are also called biosynthetic pathways.
 The synthesis of protein from amino acids is an example of anabolism.
 The energy released by catabolic pathways can be stored and then used to drive anabolic
 Energy is fundamental to all metabolic processes, and therefore an understanding of
energy is key to understanding how the living cell works.
 Bioenergetics is the study of how organisms manage their energy resources.
Organisms transform energy.
 Energy is the capacity to do work.
 Energy exists in various forms, and cells transform energy from one type into another.
 Kinetic energy is the energy associated with the relative motion of objects.
 Objects in motion can perform work by imparting motion to other matter.
 Photons of light can be captured and their energy harnessed to power photosynthesis in
green plants.
 Heat or thermal energy is kinetic energy associated with the random movement of
atoms or molecules.
 Potential energy is the energy that matter possesses because of its location or structure.
 Chemical energy is a form of potential energy stored in molecules because of the
arrangement of their atoms.
 Energy can be converted from one form to another.
 For example, as a boy climbs stairs to a diving platform, he is releasing chemical
energy stored in his cells from the food he ate for lunch.
Biology Chapter Notes
 The kinetic energy of his muscle movement is converted into potential energy as he
climbs higher.
 As he dives, the potential energy is converted back to kinetic energy.
 Kinetic energy is transferred to the water as he enters it.
 Some energy is converted to heat due to friction.
The energy transformations of life are subject to two laws of thermodynamics.
 Thermodynamics is the study of energy transformations.
 In this field, the term system refers to the matter under study and the surroundings include
everything outside the system.
 A closed system, approximated by liquid in a thermos, is isolated from its surroundings.
 In an open system, energy and matter can be transferred between the system and its
 Organisms are open systems.
 They absorb energy—light or chemical energy in the form of organic molecules—and
release heat and metabolic waste products such as urea or CO2 to their surroundings.
 The first law of thermodynamics states that energy can be transferred and transformed,
but it cannot be created or destroyed.
 The first law is also known as the principle of conservation of energy.
 Plants do not produce energy; they transform light energy to chemical energy.
 During every transfer or transformation of energy, some energy is converted to heat,
which is the energy associated with the random movement of atoms and molecules.
 A system can use heat to do work only when there is a temperature difference that results
in heat flowing from a warmer location to a cooler one.
 If temperature is uniform, as in a living cell, heat can only be used to warm the
 Energy transfers and transformations make the universe more disordered due to this loss
of usable energy.
 Entropy is a quantity used as a measure of disorder or randomness.
 The more random a collection of matter, the greater its entropy.
 The second law of thermodynamics states that every energy transfer or transformation
increases the entropy of the universe.
 While order can increase locally, there is an unstoppable trend toward randomization
of the universe.
 Much of the increased entropy of the universe takes the form of increasing heat, which
is the energy of random molecular motion.
 In most energy transformations, ordered forms of energy are converted at least partly to
 Automobiles convert only 25% of the energy in gasoline into motion; the rest is lost as
 Living cells unavoidably convert organized forms of energy to heat.
 For a process to occur on its own, without outside help in the form of energy input, it must
increase the entropy of the universe.
 The word spontaneous describes a process that can occur without an input of energy.
 Spontaneous processes need not occur quickly.
Biology Chapter Notes
 Some spontaneous processes are instantaneous, such as an explosion. Some are very
slow, such as the rusting of an old car.
 Another way to state the second law of thermodynamics is for a process to occur
spontaneously, it must increase the entropy of the universe.
 Living systems create ordered structures from less ordered starting materials.
 For example, amino acids are ordered into polypeptide chains.
 The structure of a multicellular body is organized and complex.
 However, an organism also takes in organized forms of matter and energy from its
surroundings and replaces them with less ordered forms.
 For example, an animal consumes organic molecules as food and catabolizes them to
low-energy carbon dioxide and water.
 Over evolutionary time, complex organisms have evolved from simpler ones.
 This increase in organization does not violate the second law of thermodynamics.
 The entropy of a particular system, such as an organism, may decrease as long as the
total entropy of the universe—the system plus its surroundings—increases.
 Organisms are islands of low entropy in an increasingly random universe.
 The evolution of biological order is perfectly consistent with the laws of

Concept 8.2 The free-energy change of a reaction tells us whether the reaction occurs
 How can we determine which reactions occur spontaneously and which ones require an
input of energy?
 The concept of free energy provides a useful function for measuring spontaneity of a
 Free energy is the portion of a system’s energy that is able to perform work when
temperature and pressure is uniform throughout the system, as in a living cell.
 The free energy (G) in a system is related to the total enthalpy (in biological systems,
equivalent to energy) (H) and the entropy (S) by this relationship:
 G = H − TS, where T is temperature in Kelvin units.
 Increases in temperature amplify the entropy term.
 Not all the energy in a system is available for work because the entropy component
must be subtracted from the enthalpy component.
 What remains is the free energy that is available for work.
 Free energy can be thought of as a measure of the stability of a system.
 Systems that are high in free energy—compressed springs, separated charges, organic
polymers—are unstable and tend to move toward a more stable state, one with less free
 Systems that tend to change spontaneously are those that have high enthalpy, low
entropy, or both.
 In any spontaneous process, the free energy of a system decreases.
 We can represent this change in free energy from the start of a process until its finish by:
 G = Gfinal state − Gstarting state
 Or G = H − TS
Biology Chapter Notes
 For a process to be spontaneous, the system must either give up enthalpy (decrease in H),
give up order (increase in S), or both.
 G must be negative for a process to be spontaneous.
 Every spontaneous process is characterized by a decrease in the free energy of the
 Processes that have a positive or zero G are never spontaneous.
 The greater the decrease in free energy, the more work a spontaneous process can
 Nature runs “downhill.”
 A system at equilibrium is at maximum stability.
 In a chemical reaction at equilibrium, the rates of forward and backward reactions are
equal, and there is no change in the concentration of products or reactants.
 At equilibrium G = 0, and the system can do no work.
 A process is spontaneous and can perform work only when it is moving toward
 Movements away from equilibrium are nonspontaneous and require the addition of
energy from an outside energy source (the surroundings).
 Chemical reactions can be classified as either exergonic or endergonic based on free
 An exergonic reaction proceeds with a net release of free energy; G is negative.
 The magnitude of G for an exergonic reaction is the maximum amount of work the
reaction can perform.
 The greater the decrease in free energy, the greater the amount of work that can be done.
 For the overall reaction of cellular respiration: C6H12O6 + 6O2 -> 6CO2 + 6H2O
 G = −686 kcal/mol
 For each mole (180 g) of glucose broken down by respiration, 686 kcal of energy are
made available to do work in the cell.
 The products have 686 kcal less free energy than the reactants.
 An endergonic reaction is one that absorbs free energy from its surroundings.
 Endergonic reactions store energy in molecules; G is positive.
 Endergonic reactions are nonspontaneous, and the magnitude of G is the quantity of
energy required to drive the reaction.
 If cellular respiration releases 686 kcal, then photosynthesis, the reverse reaction, must
require an equivalent investment of energy.
 For the conversion of carbon dioxide and water to sugar, G = +686 kcal/mol.
 Photosynthesis is strongly endergonic, powered by the absorption of light energy.
 Reactions in a closed system eventually reach equilibrium and can do no work.
 A cell that has reached metabolic equilibrium has a G = 0 and is dead!
 Metabolic disequilibrium is one of the defining features of life.
 Cells maintain disequilibrium because they are open systems. The constant flow of
materials into and out of the cell keeps metabolic pathways from ever reaching
 A cell continues to do work throughout its life.

Biology Chapter Notes

 A catabolic process in a cell releases free energy in a series of reactions, not in a single
 Some reversible reactions of respiration are constantly “pulled” in one direction, as the
product of one reaction does not accumulate but becomes the reactant in the next step.
 Sunlight provides a daily source of free energy for photosynthetic organisms.
 Nonphotosynthetic organisms depend on a transfer of free energy from photosynthetic
organisms in the form of organic molecules.

Concept 8.3 ATP powers cellular work by coupling exergonic reactions to endergonic
 A cell does three main kinds of work:
10.Mechanical work, such as the beating of cilia, contraction of muscle cells, and
movement of chromosomes during cellular reproduction.
11.Transport work, the pumping of substances across membranes against the direction of
spontaneous movement.
12.Chemical work, driving endergonic reactions such as the synthesis of polymers from
 Cells manage their energy resources to do this work by energy coupling, the use of an
exergonic process to drive an endergonic one.
 In most cases, the immediate source of energy to power cellular work is ATP.
 ATP (adenosine triphosphate) is a type of nucleotide consisting of the nitrogenous base
adenine, the sugar ribose, and a chain of three phosphate groups.
 The bonds between phosphate groups can be broken by hydrolysis.
 Hydrolysis of the end phosphate group forms adenosine diphosphate.
 ATP -> ADP + Pi
 This reaction releases 7.3 kcal of energy per mole of ATP under standard
conditions (1 M of each reactant and product, 25°C, pH 7).
 In the cell, G for hydrolysis of ATP is about −13 kcal/mol.
 While the phosphate bonds of ATP are sometimes referred to as high-energy phosphate
bonds, these are actually fairly weak covalent bonds.
 However, they are unstable, and their hydrolysis yields energy because the products
are more stable.
 The release of energy during the hydrolysis of ATP comes from the chemical change to a
state of lower free energy, not from the phosphate bonds themselves.
 Why does the hydrolysis of ATP yield so much energy?
 Each of the three phosphate groups has a negative charge.
 These three like charges are crowded together, and their mutual repulsion contributes
to the instability of this region of the ATP molecule.
 In the cell, the energy from the hydrolysis of ATP is directly coupled to endergonic
processes by the transfer of the phosphate group to another molecule.
 This recipient molecule is now phosphorylated.
 This molecule is now more reactive (less stable) than the original unphosphorylated

Biology Chapter Notes

 Mechanical, transport, and chemical work in the cell are nearly always powered by the
hydrolysis of ATP.
 In each case, a phosphate group is transferred from ATP to another molecule and the
phosphorylated molecule undergoes a change that performs work.
 ATP is a renewable resource that can be regenerated by the addition of a phosphate group
to ADP.
 The energy to phosphorylate ADP comes from catabolic reactions in the cell.
 A working muscle cell recycles its entire pool of ATP once each minute.
 More than 10 million ATP molecules are consumed and regenerated per second per
 Regeneration of ATP is an endergonic process, requiring an investment of energy.
 G = 7.3 kcal/mol.
 Catabolic (exergonic) pathways, especially cellular respiration, provide the energy for the
exergonic regeneration of ATP.
 The chemical potential energy temporarily stored in ATP drives most cellular work.

Concept 8.4 Enzymes speed up metabolic reactions by lowering energy barriers

 Spontaneous chemical reactions may occur so slowly as to be imperceptible.
 The hydrolysis of table sugar (sucrose) to glucose and fructose is exergonic.
 G = −7 kcal/mol
 Despite this, your sugar sits in its bowl with no observable hydrolysis.
 If we add a small amount of the enzyme catalyst sucrase to a solution of sugar, all the
sucrose will be hydrolyzed within seconds.
 A catalyst is a chemical agent that speeds up the rate of a reaction without being
consumed by the reaction.
 An enzyme is a catalytic protein.
 Enzymes regulate metabolic pathways.
 Every chemical reaction involves bond breaking and bond forming.
 To hydrolyze sucrose, the bond between glucose and fructose must be broken and new
bonds must form with hydrogen and hydroxyl ions from water.
 To reach a state where bonds can break and reform, reactant molecules must absorb
energy from their surroundings. When the new bonds of the product molecules form,
energy is released as heat as the molecules assume stable shapes with lower energy.
 The initial investment of energy for starting a reaction is the free energy of activation or
activation energy (EA).
 Activation energy is the amount of energy necessary to push the reactants over an energy
barrier so that the reaction can proceed.
 At the summit, the molecules are in an unstable condition, the transition state.
 Activation energy may be supplied in the form of heat that the reactant molecules
absorb from the surroundings.
 The bonds of the reactants break only when the molecules have absorbed enough
energy to become unstable and, therefore, more reactive.
 The absorption of thermal energy increases the speed of the reactant molecules, so they
collide more often and more forcefully.
Biology Chapter Notes
 Thermal agitation of the atoms in the molecules makes bonds more likely to break.
 As the molecules settle into new, stable bonding arrangements, energy is released to
the surroundings.
 In exergonic reactions, the activation energy is released back to the surroundings, and
additional energy is released with the formation of new bonds.
 For some processes, EA is not high, and the thermal energy provided by room temperature
is sufficient for many reactants to reach the transition state.
 In many cases, EA is high enough that the transition state is rarely reached and that the
reaction hardly proceeds at all. In these cases, the reaction will only occur at a noticeable
rate if the reactants are heated.
 A spark plug provides the energy to energize a gasoline-oxygen mixture and cause
 Without that activation energy, the hydrocarbons of gasoline are too stable to react
with oxygen.
 Proteins, DNA, and other complex organic molecules are rich in free energy. Their
hydrolysis is spontaneous, with the release of large amounts of energy.
 However, there is not enough energy at the temperatures typical of the cell for the vast
majority of organic molecules to make it over the hump of activation energy.
 How are the barriers for selected reactions surmounted to allow cells to carry out the
processes of life?
 Heat would speed up reactions, but it would also denature proteins and kill cells.
 Enzymes speed reactions by lowering EA.
 The transition state can then be reached even at moderate temperatures.
 Enzymes do not change G.
 They hasten reactions that would occur eventually.
 Because enzymes are so selective, they determine which chemical processes will occur
at any time.
Enzymes are substrate specific.
 The reactant that an enzyme acts on is the substrate.
 The enzyme binds to a substrate, or substrates, forming an enzyme-substrate complex.
 While the enzyme and substrate are bound, the catalytic action of the enzyme converts the
substrate to the product or products.
 The reaction catalyzed by each enzyme is very specific.
 What accounts for this molecular recognition?
 The specificity of an enzyme results from its three-dimensional shape.
 Only a portion of the enzyme binds to the substrate.
 The active site of an enzyme is typically a pocket or groove on the surface of the
protein into which the substrate fits.
 The active site is usually formed by only a few amino acids.
 The specificity of an enzyme is due to the fit between the active site and the substrate.
 As the substrate enters the active site, interactions between the substrate and the amino
acids of the protein causes the enzyme to change shape slightly, leading to a tighter
induced fit that brings chemical groups in position to catalyze the reaction.

Biology Chapter Notes

The active site is an enzyme’s catalytic center.
 In most cases, substrates are held in the active site by weak interactions, such as hydrogen
bonds and ionic bonds.
 R groups of a few amino acids on the active site catalyze the conversion of substrate to
 The product then leaves the active site.
 A single enzyme molecule can catalyze thousands of reactions a second.
 Enzymes are unaffected by the reaction and are reusable.
 Most metabolic enzymes can catalyze a reaction in both the forward and reverse
 The actual direction depends on the relative concentrations of products and reactants.
 Enzymes catalyze reactions in the direction of equilibrium.
 Enzymes use a variety of mechanisms to lower activation energy and speed up a reaction.
 In reactions involving more than one reactant, the active site brings substrates together
in the correct orientation for the reaction to proceed.
 As the active site binds the substrate, it may put stress on bonds that must be broken,
making it easier for the reactants to reach the transition state.
 R groups at the active site may create a microenvironment that is conducive to a
specific reaction.
 An active site may be a pocket of low pH, facilitating H+ transfer to the substrate as
a key step in catalyzing the reaction.
 Enzymes may briefly bind covalently to substrates.
 Subsequent steps of the reaction restore the R groups within the active site to their
original state.
 The rate that a specific number of enzymes convert substrates to products depends in part
on substrate concentrations.
 At low substrate concentrations, an increase in substrate concentration speeds binding
to available active sites.
 However, there is a limit to how fast a reaction can occur.
 At high substrate concentrations, the active sites on all enzymes are engaged.
 The enzyme is saturated.
 The rate of the reaction is determined by the speed at which the active site can
convert substrate to product.
 The only way to increase productivity at this point is to add more enzyme molecules.
A cell’s physical and chemical environment affects enzyme activity.
 The activity of an enzyme is affected by general environmental conditions, such as
temperature and pH.
 Each enzyme works best at certain optimal conditions, which favor the most active
conformation for the enzyme molecule.
 Temperature has a major impact on reaction rate.
 As temperature increases, collisions between substrates and active sites occur more
frequently as molecules move more rapidly.
 As temperature increases further, thermal agitation begins to disrupt the weak bonds
that stabilize the protein’s active conformation, and the protein denatures.
Biology Chapter Notes
 Each enzyme has an optimal temperature.
 Most human enzymes have optimal temperatures of about 35–40°C.
 Bacteria that live in hot springs contain enzymes with optimal temperatures of 70°C
or above.
 Each enzyme also has an optimal pH.
 Maintenance of the active conformation of the enzyme requires a particular pH.
 This falls between pH 6 and 8 for most enzymes.
 However, digestive enzymes in the stomach are designed to work best at pH 2, while
those in the intestine have an optimum of pH 8.
 Many enzymes require nonprotein helpers, called cofactors, for catalytic activity.
 Cofactors bind permanently or reversibly to the enzyme.
 Some inorganic cofactors include zinc, iron, and copper.
 Organic cofactors are called coenzymes.
 Many vitamins are coenzymes.
 Binding by inhibitors prevents enzymes from catalyzing reactions.
 If inhibitors attach to the enzyme by covalent bonds, inhibition may be irreversible.
 If inhibitors bind by weak bonds, inhibition may be reversible.
 Some reversible inhibitors resemble the substrate and compete for binding to the active
 These molecules are called competitive inhibitors.
 Competitive inhibition can be overcome by increasing the concentration of the
 Noncompetitive inhibitors impede enzymatic reactions by binding to another part of the
 Binding by the inhibitor causes the enzyme to change shape, rendering the active site
less effective at catalyzing the reaction.
 Toxins and poisons are often irreversible enzyme inhibitors.
 Sarin is the nerve gas that was released by terrorists in the Tokyo subway in 1995.
 Sarin binds covalently to the R group on the amino acid serine.
 Serine is found in the active site of acetylcholinesterase, an important nervous system

Concept 8.5 Regulation of enzyme activity helps control metabolism

Metabolic control often depends on allosteric regulation.
 In many cases, the molecules that naturally regulate enzyme activity behave like
reversible noncompetitive inhibitors.
 Regulatory molecules often bind weakly to an allosteric site, a specific receptor on the
enzyme away from the active site.
 Binding by these molecules can either inhibit or stimulate enzyme activity.
 Most allosterically regulated enzymes are constructed of two or more polypeptide chains.
 Each subunit has its own active site.
 Allosteric sites are often located where subunits join.
Biology Chapter Notes
 The binding of an activator stabilizes the conformation that has functional active sites,
while the binding of an inhibitor stabilizes the inactive form of the enzyme.
 As the chemical conditions in the cell shift, the pattern of allosteric regulation may shift as
 By binding to key enzymes, reactants and products of ATP hydrolysis may play a major
role in balancing the flow of traffic between anabolic and catabolic pathways.
 For example, ATP binds to several catabolic enzymes allosterically, inhibiting their
activity by lowering their affinity for substrate.
 ADP functions as an activator of the same enzymes.
 ATP and ADP also affect key enzymes in anabolic pathways.
 In this way, allosteric enzymes control the rates of key reactions in metabolic
 In enzymes with multiple catalytic subunits, binding by a substrate to one active site
stabilizes favorable conformational changes at all other subunits, a process called
 This mechanism amplifies the response of enzymes to substrates, priming the enzyme
to accept additional substrates.
 A common method of metabolic control is feedback inhibition in which an early step in a
metabolic pathway is switched off by the pathway’s final product.
 The product acts as an inhibitor of an enzyme in the pathway.
 Feedback inhibition prevents a cell from wasting chemical resources by synthesizing more
product than is needed.
The localization of enzymes within a cell helps order metabolism.
 Structures within the cell help bring order to metabolic pathways.
 A team of enzymes for several steps of a metabolic pathway may be assembled as a
multienzyme complex.
 The product from the first reaction can then pass quickly to the next enzyme until the final
product is released.
 Some enzymes and enzyme complexes have fixed locations within the cells as structural
components of particular membranes.
 Others are confined within membrane-enclosed eukaryotic organelles.
 Metabolism, the intersecting set of chemical pathways characteristic of life, is a
choreographed interplay of thousands of different kinds of cellular molecules.

Biology Chapter Notes

Chapter 9 Cellular Respiration: Harvesting Chemical
Chapter Notes

Overview: Life Is Work

 To perform their many tasks, living cells require energy from outside sources.
 Energy enters most ecosystems as sunlight and leaves as heat.
 Photosynthesis generates oxygen and organic molecules that the mitochondria of
eukaryotes use as fuel for cellular respiration.
 Cells harvest the chemical energy stored in organic molecules and use it to regenerate
ATP, the molecule that drives most cellular work.
 Respiration has three key pathways: glycolysis, the citric acid cycle, and oxidative

Concept 9.1 Catabolic pathways yield energy by oxidizing organic fuels

 The arrangement of atoms of organic molecules represents potential energy.
 Enzymes catalyze the systematic degradation of organic molecules that are rich in energy
to simpler waste products with less energy.
 Some of the released energy is used to do work; the rest is dissipated as heat.
 Catabolic metabolic pathways release the energy stored in complex organic molecules.
 One type of catabolic process, fermentation, leads to the partial degradation of sugars in
the absence of oxygen.
 A more efficient and widespread catabolic process, cellular respiration, consumes
oxygen as a reactant to complete the breakdown of a variety of organic molecules.
 In eukaryotic cells, mitochondria are the site of most of the processes of cellular
 Cellular respiration is similar in broad principle to the combustion of gasoline in an
automobile engine after oxygen is mixed with hydrocarbon fuel.
 Food is the fuel for respiration. The exhaust is carbon dioxide and water.
 The overall process is:
 organic compounds + O2  CO2 + H2O + energy (ATP + heat).
 Carbohydrates, fats, and proteins can all be used as the fuel, but it is most useful to
consider glucose.
 C6H12O6 + 6O2  6CO2 + 6H2O + Energy (ATP + heat)
 The catabolism of glucose is exergonic with a  G of −686 kcal per mole of glucose.
 Some of this energy is used to produce ATP, which can perform cellular work.
Redox reactions release energy when electrons move closer to electronegative atoms.

Biology Chapter Notes

 Catabolic pathways transfer the electrons stored in food molecules, releasing energy that
is used to synthesize ATP.
 Reactions that result in the transfer of one or more electrons from one reactant to another
are oxidation-reduction reactions, or redox reactions.
 The loss of electrons is called oxidation.
 The addition of electrons is called reduction.
 The formation of table salt from sodium and chloride is a redox reaction.
 Na + Cl  Na+ + Cl−
 Here sodium is oxidized and chlorine is reduced (its charge drops from 0 to −1).
 More generally: Xe− + Y  X + Ye−
 X, the electron donor, is the reducing agent and reduces Y.
 Y, the electron recipient, is the oxidizing agent and oxidizes X.
 Redox reactions require both a donor and acceptor.
 Redox reactions also occur when the transfer of electrons is not complete but involves a
change in the degree of electron sharing in covalent bonds.
 In the combustion of methane to form water and carbon dioxide, the nonpolar covalent
bonds of methane (C—H) and oxygen (O=O) are converted to polar covalent bonds
(C=O and O—H).
 When methane reacts with oxygen to form carbon dioxide, electrons end up farther
away from the carbon atom and closer to their new covalent partners, the oxygen
atoms, which are very electronegative.
 In effect, the carbon atom has partially “lost” its shared electrons. Thus, methane has
been oxidized.
 The two atoms of the oxygen molecule share their electrons equally. When oxygen reacts
with the hydrogen from methane to form water, the electrons of the covalent bonds are
drawn closer to the oxygen.
 In effect, each oxygen atom has partially “gained” electrons, and so the oxygen
molecule has been reduced.
 Oxygen is very electronegative, and is one of the most potent of all oxidizing agents.
 Energy must be added to pull an electron away from an atom.
 The more electronegative the atom, the more energy is required to take an electron away
from it.
 An electron loses potential energy when it shifts from a less electronegative atom toward
a more electronegative one.
 A redox reaction that relocates electrons closer to oxygen, such as the burning of methane,
releases chemical energy that can do work.
The “fall” of electrons during respiration is stepwise, via NAD+ and an electron transport
 Cellular respiration does not oxidize glucose in a single step that transfers all the
hydrogen in the fuel to oxygen at one time.
 Rather, glucose and other fuels are broken down in a series of steps, each catalyzed by a
specific enzyme.
 At key steps, electrons are stripped from the glucose.
 In many oxidation reactions, the electron is transferred with a proton, as a hydrogen
Biology Chapter Notes
 The hydrogen atoms +are not transferred directly to oxygen but are passed first to a
coenzyme called NAD (nicotinamide adenine dinucleotide).
 How does NAD+ trap electrons from glucose?
 Dehydrogenase enzymes strip two hydrogen atoms from the fuel (e.g., glucose),
oxidizing it.

The enzyme passes two electrons and one proton to NAD+.

The other proton is released as H+ to the surrounding solution.
 By receiving two electrons and only one proton, NAD + has its charge neutralized when it
is reduced to NADH.
 NAD+ functions as the oxidizing agent in many of the redox steps during the
catabolism of glucose.
 The electrons carried by NADH have lost very little of their potential energy in this
 Each NADH molecule formed during respiration represents stored energy. This energy is
tapped to synthesize ATP as electrons “fall” from NADH to oxygen.
 How are electrons extracted from food and stored by NADH finally transferred to
 Unlike the explosive release of heat energy that occurs when H 2 and O2 are combined
(with a spark for activation energy), cellular respiration uses an electron transport
chain to break the fall of electrons to O2 into several steps.
 The electron transport chain consists of several molecules (primarily proteins) built into
the inner membrane of a mitochondrion.
 Electrons released from food are shuttled by NADH to the “top” higher-energy end of the
 At the “bottom” lower-energy end, oxygen captures the electrons along with H + to form
 Electron transfer from NADH to oxygen is an exergonic reaction with a free energy
change of −53 kcal/mol.
 Electrons are passed to increasingly electronegative molecules in the chain until they
reduce oxygen, the most electronegative receptor.
 In summary, during cellular respiration, most electrons travel the following “downhill”
route: food  NADH  electron transport chain  oxygen.
These are the stages of cellular respiration: a preview.
 Respiration occurs in three metabolic stages: glycolysis, the citric acid cycle, and the
electron transport chain and oxidative phosphorylation.
 Glycolysis occurs in the cytoplasm.
 It begins catabolism by breaking glucose into two molecules of pyruvate.
 The citric acid cycle occurs in the mitochondrial matrix.
 It completes the breakdown of glucose by oxidizing a derivative of pyruvate to carbon
 Several steps in glycolysis and the citric acid cycle are redox reactions in which
dehydrogenase enzymes transfer electrons from substrates to NAD+, forming NADH.
 NADH passes these electrons to the electron transport chain.

Biology Chapter Notes

 In the electron transport chain, the electrons move from molecule to molecule until they
combine with molecular oxygen and hydrogen ions to form water.
 As they are passed along the chain, the energy carried by these electrons is transformed in
the mitochondrion into a form that can be used to synthesize ATP via oxidative
 The inner membrane of the mitochondrion is the site of electron transport and
chemiosmosis, processes that together constitute oxidative phosphorylation.
 Oxidative phosphorylation produces almost 90% of the ATP generated by respiration.
 Some ATP is also formed directly during glycolysis and the citric acid cycle by
substrate-level phosphorylation.
 Here an enzyme transfers a phosphate group from an organic substrate to ADP,
forming ATP.
 For each molecule of glucose degraded to carbon dioxide and water by respiration, the
cell makes up to 38 ATP, each with 7.3 kcal/mol of free energy.
 Respiration uses the small steps in the respiratory pathway to break the large
denomination of energy contained in glucose into the small change of ATP.
 The quantity of energy in ATP is more appropriate for the level of work required in the

Concept 9.2 Glycolysis harvests chemical energy by oxidizing glucose to pyruvate

 During glycolysis, glucose, a six carbon-sugar, is split into two three-carbon sugars.
 These smaller sugars are oxidized and rearranged to form two molecules of pyruvate, the
ionized form of pyruvic acid.
 Each of the ten steps in glycolysis is catalyzed by a specific enzyme.
 These steps can be divided into two phases: an energy investment phase and an energy
payoff phase.
 In the energy investment phase, the cell invests ATP to provide activation energy by
phosphorylating glucose.
 This requires 2 ATP per glucose.
 In the+ energy payoff phase, ATP is produced by substrate-level phosphorylation and
NAD is reduced to NADH by electrons released by the oxidation of glucose.
 The net yield from glycolysis is 2 ATP and 2 NADH per glucose.
 No CO2 is produced during glycolysis.
 Glycolysis can occur whether O2 is present or not.

Concept 9.3 The citric acid cycle completes the energy-yielding oxidation of organic
 More than three-quarters of the original energy in glucose is still present in the two
molecules of pyruvate.
 If oxygen is present, pyruvate enters the mitochondrion where enzymes of the citric acid
cycle complete the oxidation of the organic fuel to carbon dioxide.

Biology Chapter Notes

 After pyruvate enters the mitochondrion via active transport, it is converted to a
compound called acetyl coenzyme A or acetyl CoA.
 This step is accomplished by a multienzyme complex that catalyzes three reactions:
o A carboxyl group is removed as CO2.
o The remaining two-carbon fragment is oxidized to form acetate. An enzyme transfers
the pair of electrons to NAD+ to form NADH.
o Acetate combines with coenzyme A to form the very reactive molecule acetyl CoA.
 Acetyl CoA is now ready to feed its acetyl group into the citric acid cycle for further
 The citric acid cycle is also called the Krebs cycle in honor of Hans Krebs, who was
largely responsible for elucidating its pathways in the 1930s.
 The citric acid cycle oxidizes organic fuel derived from pyruvate.
 The citric acid cycle has eight steps, each catalyzed by a specific enzyme.
 The acetyl group of acetyl CoA joins the cycle by combining with the compound
oxaloacetate, forming citrate.
 The next seven steps decompose the citrate back to oxaloacetate. It is the regeneration
of oxaloacetate that makes this process a cycle.
 Three CO2 molecules are released, including the one released during the conversion of
pyruvate to acetyl CoA.
 The cycle generates one ATP per turn by substrate-level phosphorylation.
 A GTP molecule is formed by substrate-level phosphorylation.
 The GTP is then used to synthesize an ATP, the only ATP generated directly by the
citric acid cycle.
 Most of the chemical energy is transferred to NAD+ and FAD during the redox reactions.
 The reduced coenzymes NADH and FADH2 then transfer high-energy electrons to the
electron transport chain.
 Each cycle produces one ATP by substrate-level phosphorylation, three NADH, and one
FADH2 per acetyl CoA.

Concept 9.4 During oxidative phosphorylation, chemiosmosis couples electron transport

to ATP synthesis
The inner mitochondrial membrane couples electron transport to ATP synthesis.
 Only 4 of 38 ATP ultimately produced by respiration of glucose are produced by
substrate-level phosphorylation.
 Two are produced during glycolysis, and 2 are produced during the citric acid cycle.
 NADH and FADH2 account for the vast majority of the energy extracted from the food.
 These reduced coenzymes link glycolysis and the citric acid cycle to oxidative
phosphorylation, which uses energy released by the electron transport chain to power
ATP synthesis.
 The electron transport chain is a collection of molecules embedded in the cristae, the
folded inner membrane of the mitochondrion.
 The folding of the cristae increases its surface area, providing space for thousands of
copies of the chain in each mitochondrion.

Biology Chapter Notes

 Most components of the chain are proteins bound to prosthetic groups, nonprotein
components essential for catalysis.
 Electrons drop in free energy as they pass down the electron transport chain.
 During electron transport along the chain, electron carriers alternate between reduced and
oxidized states as they accept and donate electrons.
 Each component of the chain becomes reduced when it accepts electrons from its
“uphill” neighbor, which is less electronegative.
 It then returns to its oxidized form as it passes electrons to its more electronegative
“downhill” neighbor.
 Electrons carried by NADH are transferred to the first molecule in the electron transport
chain, a flavoprotein.
 The electrons continue along the chain that includes several cytochrome proteins and one
lipid carrier.
 The prosthetic group of each cytochrome is a heme group with an iron atom that
accepts and donates electrons.
 The last cytochrome of the chain, cyt a3, passes its electrons to oxygen, which is very
 Each oxygen atom also picks up a pair of hydrogen ions from the aqueous solution to
form water.
 For every two electron carriers (four electrons), one O2 molecule is reduced to two
molecules of water.
 The electrons carried by FADH2 have lower free energy and are added at a lower energy
level than those carried by NADH.
 The electron transport chain provides about one-third less energy for ATP synthesis
when the electron donor is FADH2 rather than NADH.
 The electron transport chain generates no ATP directly.
 Its function is to break the large free energy drop from food to oxygen into a series of
smaller steps that release energy in manageable amounts.
 How does the mitochondrion couple electron transport and energy release to ATP
 The answer is a mechanism called chemiosmosis.
 A protein complex, ATP synthase, in the cristae actually makes ATP from ADP and Pi.
 ATP uses the energy of an existing proton gradient to power ATP synthesis.
 The proton gradient develops between the intermembrane space and the matrix.
 The proton gradient is produced by the movement of electrons along the electron transport
 The chain is an energy converter that uses the exergonic flow of electrons to pump H +
from the matrix into the intermembrane space.
 The protons pass back to the matrix through a channel in ATP synthase, using the
exergonic flow of H+ to drive the phosphorylation of ADP.
 Thus, the energy stored in a H+ gradient across a membrane couples the redox reactions of
the electron transport chain to ATP synthesis.
 From studying the structure of ATP synthase, scientists have learned how the flow of H+
through this large enzyme powers ATP generation.
Biology Chapter Notes
 ATP synthase is a multisubunit complex with four main parts, each made up of multiple
o A rotor in the inner mitochondrial membrane.
o A knob that protrudes into the mitochondrial matrix.
o An internal rod extending from the rotor into the knob.
o A stator, anchored next to the rotor, which holds the knob stationary.
 Protons flow down a narrow space between the stator and rotor, causing the rotor and its
attached rod to rotate.
 The spinning rod causes conformational changes in the stationary knob, activating
three catalytic sites in the knob where ADP and inorganic phosphate combine to make
 How does the inner mitochondrial membrane generate and maintain the H + gradient that
drives ATP synthesis in the ATP synthase protein complex?
 Creating the H+ gradient is the function of the electron transport chain.
 The ETC is an energy converter that uses the exergonic flow of electrons to pump H +
across the membrane from the mitochondrial matrix to the intermembrane space.
 The H+ has a tendency to diffuse down its gradient.
 The ATP synthase molecules are the only place that H+ can diffuse back to the matrix.
 The exergonic flow of H+ is used by the enzyme to generate ATP.
 This coupling of the redox reactions of the electron transport chain to ATP synthesis is
called chemiosmosis.
 How does the electron transport chain pump protons?
 Certain members of the electron transport chain accept and release H + along with
 At certain steps along the chain, electron transfers cause H+ to be taken up and released
into the surrounding solution.
 The electron carriers are spatially arranged in the membrane in such a way that protons
are accepted from the mitochondrial matrix and deposited in the intermembrane space.
 The H+ gradient that results is the proton-motive force.
 The gradient has the capacity to do work.
 Chemiosmosis is an energy-coupling mechanism that uses energy stored in the form of an
H+ gradient across a membrane to drive cellular work.
 In mitochondria, the energy for proton gradient formation comes from exergonic redox
reactions, and ATP synthesis is the work performed.
 Chemiosmosis in chloroplasts also+ generates ATP, but light drives the electron flow down
an electron transport chain and H gradient formation.
 Prokaryotes generate H+ gradients across their plasma membrane.
 They can use this proton-motive force not only to generate ATP, but also to pump
nutrients and waste products across the membrane and to rotate their flagella.
Here is an accounting of ATP production by cellular respiration.
 During cellular respiration, most energy flows from glucose  NADH  electron
transport chain  proton-motive force  ATP.
 Let’s consider the products generated when cellular respiration oxidizes a molecule of
glucose to six CO2 molecules.
Biology Chapter Notes
 Four ATP molecules are produced by substrate-level phosphorylation during glycolysis
and the citric acid cycle.
 Many more ATP molecules are generated by oxidative phosphorylation.
 Each NADH from the citric acid cycle and the conversion of pyruvate contributes enough
energy to the proton-motive force to generate a maximum of 3 ATP.
 The NADH from glycolysis may also yield 3 ATP.
 Each FADH2 from the citric acid cycle can be used to generate about 2 ATP.
 Why is our accounting so inexact?
 There are three reasons that we cannot state an exact number of ATP molecules generated
by one molecule of glucose.
o Phosphorylation and the redox reactions are not directly coupled to each other, so the
ratio of number of NADH to number of ATP is not a whole number.
 One NADH results in 10 H+ being transported across the inner mitochondrial
 Between 3 and 4 H+ must reenter the mitochondrial matrix via ATP synthase to
generate 1 ATP.
 Therefore, 1 NADH generates enough proton-motive force for synthesis of 2.5 to 3.3
 We round off and say that 1 NADH generates 3 ATP.
o The ATP yield varies slightly depending on the type of shuttle used to transport
electrons from the cytosol into the mitochondrion.
 The mitochondrial inner membrane is impermeable to NADH, so the two electrons of
the NADH produced in glycolysis must be conveyed into the mitochondrion by one of
several electron shuttle systems.
 In some shuttle systems, the electrons are passed to NAD +, which generates 3 ATP. In
others, the electrons are passed to FAD, which generates only 2 ATP.
o The proton-motive force generated by the redox reactions of respiration may drive
other kinds of work, such as mitochondrial uptake of pyruvate from the cytosol.
 If all the proton-motive force generated by the electron transport chain were used to
drive ATP synthesis, one glucose molecule could generate a maximum of 34 ATP by
oxidative phosphorylation plus 4 ATP (net) from substrate-level phosphorylation to
give a total yield of 36–38 ATP (depending on the efficiency of the shuttle).
 How efficient is respiration in generating ATP?
 Complete oxidation of glucose releases 686 kcal/mol.
 Phosphorylation of ADP to form ATP requires at least 7.3 kcal/mol.
 Efficiency of respiration is 7.3 kcal/mol times 38 ATP/glucose divided by 686
kcal/mol glucose, which equals 0.4 or 40%.
 Approximately 60% of the energy from glucose is lost as heat.
 Some of that heat is used to maintain our high body temperature (37°C).
 Cellular respiration is remarkably efficient in energy conversion.

Concept 9.5 Fermentation enables some cells to produce ATP without the use of oxygen
 Without electronegative oxygen to pull electrons down the transport chain, oxidative
phosphorylation ceases.

Biology Chapter Notes

 However, fermentation provides a mechanism by which some cells can oxidize organic
fuel and generate ATP without the use of oxygen.
 In glycolysis, glucose is oxidized to two pyruvate molecules with NAD + as the
oxidizing agent.
 Glycolysis is exergonic and produces 2 ATP (net).
 If oxygen is present, additional ATP can be generated when NADH delivers its
electrons to the electron transport chain.
 Glycolysis generates 2 ATP whether oxygen is present (aerobic) or not (anaerobic).
 Anaerobic catabolism of sugars can occur by fermentation.
 Fermentation can generate ATP from glucose by substrate-level phosphorylation as long
as there is a supply of NAD+ to accept electrons.
 If the NAD+ pool is exhausted, glycolysis shuts down.
 Under aerobic conditions, NADH transfers its electrons to the electron transfer chain,
recycling NAD+.
 Under anaerobic conditions, various fermentation pathways generate ATP by glycolysis
and recycle NAD+ by transferring electrons from NADH to pyruvate or derivatives of
 In alcohol fermentation, pyruvate is converted to ethanol in two steps.
 First, pyruvate is converted to a two-carbon compound, acetaldehyde, by the removal
of CO2.
 Second, acetaldehyde is reduced by NADH to ethanol.
 Alcohol fermentation by yeast is used in brewing and winemaking.
 During lactic acid fermentation, pyruvate is reduced directly by NADH to form lactate
(the ionized form of lactic acid) without release of CO2.
 Lactic acid fermentation by some fungi and bacteria is used to make cheese and
 Human muscle cells switch from aerobic respiration to lactic acid fermentation to
generate ATP when O2 is scarce.
 The waste product, lactate, may cause muscle fatigue, but ultimately it is converted
back to pyruvate in the liver.
 Fermentation and cellular respiration are anaerobic and aerobic alternatives, respectively,
for producing ATP from sugars.
 Both use glycolysis to oxidize sugars to pyruvate with a net production of 2 ATP by
substrate-level phosphorylation.
 Both use NAD+ as an oxidizing agent to accept electrons from food during glycolysis.
 The two processes differ in their mechanism for oxidizing NADH to NAD+.
 In fermentation,+ the electrons of NADH are passed to an organic molecule to
regenerate NAD .
 In respiration, the electrons of NADH are ultimately passed to O 2, generating ATP by
oxidative phosphorylation.
 More ATP is generated from the oxidation of pyruvate in the citric acid cycle.
 Without oxygen, the energy still stored in pyruvate is unavailable to the cell.
 Under aerobic respiration, a molecule of glucose yields 38 ATP, but the same molecule
of glucose yields only 2 ATP under anaerobic respiration.

Biology Chapter Notes

 Yeast and many bacteria are facultative anaerobes that can survive using either
fermentation or respiration.
 At a cellular level, human muscle cells can behave as facultative anaerobes.
 For facultative anaerobes, pyruvate is a fork in the metabolic road that leads to two
alternative routes.
 Under aerobic conditions, pyruvate is converted to acetyl CoA and oxidation continues
in the citric acid cycle.
 Under anaerobic conditions, pyruvate serves as an electron acceptor to recycle NAD+.
 The oldest bacterial fossils are more than 3.5 billion years old, appearing long before
appreciable quantities of O2 accumulated in the atmosphere.
 Therefore, the first prokaryotes may have generated ATP exclusively from glycolysis.
 The fact that glycolysis is a ubiquitous metabolic pathway and occurs in the cytosol
without membrane-enclosed organelles suggests that glycolysis evolved early in the
history of life.

Concept 9.6 Glycolysis and the citric acid cycle connect to many other metabolic
 Glycolysis can accept a wide range of carbohydrates for catabolism.
 Polysaccharides like starch or glycogen can be hydrolyzed to glucose monomers that
enter glycolysis.
 Other hexose sugars, such as galactose and fructose, can also be modified to undergo
 The other two major fuels, proteins and fats, can also enter the respiratory pathways used
by carbohydrates.
 Proteins must first be digested to individual amino acids.
 Amino acids that will be catabolized must have their amino groups removed via
 The nitrogenous waste is excreted as ammonia, urea, or another waste product.
 The carbon skeletons are modified by enzymes and enter as intermediaries into glycolysis
or the citric acid cycle, depending on their structure.
 Catabolism can also harvest energy stored in fats.
 Fats must be digested to glycerol and fatty acids.
 Glycerol can be converted to glyceraldehyde phosphate, an intermediate of glycolysis.
 The rich energy of fatty acids is accessed as fatty acids are split into two-carbon
fragments via beta oxidation.
 These molecules enter the citric acid cycle as acetyl CoA.
 A gram of fat oxides by respiration generates twice as much ATP as a gram of
 The metabolic pathways of respiration also play a role in anabolic pathways of the cell.
 Intermediaries in glycolysis and the citric acid cycle can be diverted to anabolic pathways.
 For example, a human cell can synthesize about half the 20 different amino acids by
modifying compounds from the citric acid cycle.
 Glucose can be synthesized from pyruvate; fatty acids can be synthesized from acetyl
Biology Chapter Notes
 Glycolysis and the citric acid cycle function as metabolic interchanges that enable cells to
convert one kind of molecule to another as needed.
 For example, excess carbohydrates and proteins can be converted to fats through
intermediaries of glycolysis and the citric acid cycle.
 Metabolism is remarkably versatile and adaptable.
Feedback mechanisms control cellular respiration.
 Basic principles of supply and demand regulate the metabolic economy.
 If a cell has an excess of a certain amino acid, it typically uses feedback inhibition to
prevent the diversion of intermediary molecules from the citric acid cycle to the
synthesis pathway of that amino acid.
 The rate of catabolism is also regulated, typically by the level of ATP in the cell.
 If ATP levels drop, catabolism speeds up to produce more ATP.
 Control of catabolism is based mainly on regulating the activity of enzymes at strategic
points in the catabolic pathway.
 One strategic point occurs in the third step of glycolysis, catalyzed by
 Allosteric regulation of phosphofructokinase sets the pace of respiration.
 This enzyme catalyzes the earliest step that irreversibly commits the substrate to
 Phosphofructokinase is an allosteric enzyme with receptor sites for specific inhibitors
and activators.
 It is inhibited by ATP and stimulated by AMP (derived from ADP).
 When ATP levels are high, inhibition of this enzyme slows glycolysis.
 As ATP levels drop and ADP and AMP levels rise, the enzyme becomes active
again and glycolysis speeds up.
 Citrate, the first product of the citric acid cycle, is also an inhibitor of
 This synchronizes the rate of glycolysis and the citric acid cycle.
 If intermediaries from the citric acid cycle are diverted to other uses (e.g., amino acid
synthesis), glycolysis speeds up to replace these molecules.
 Metabolic balance is augmented by the control of other enzymes at other key locations in
glycolysis and the citric acid cycle.
 Cells are thrifty, expedient, and responsive in their metabolism.

Biology Chapter Notes

Chapter 10 Photosynthesis
Chapter Notes

Overview: The Process That Feeds the Biosphere

 Life on Earth is solar powered.

 The chloroplasts of plants use a process called photosynthesis to capture light energy from
the sun and convert it to chemical energy stored in sugars and other organic molecules.
Plants and other autotrophs are the producers of the biosphere.
 Photosynthesis nourishes almost all the living world directly or indirectly.
 All organisms use organic compounds for energy and for carbon skeletons.
 Organisms obtain organic compounds by one of two major modes: autotrophic
nutrition or heterotrophic nutrition.
 Autotrophs produce their organic molecules from CO2 and other inorganic raw materials
obtained from the environment.
 Autotrophs are the ultimate sources of organic compounds for all heterotrophic
 Autotrophs are the producers of the biosphere.
 Autotrophs can be separated by the source of energy that drives their metabolism.
 Photoautotrophs use light as a source of energy to synthesize organic compounds.
 Photosynthesis occurs in plants, algae, some other protists, and some prokaryotes.
 Chemoautotrophs harvest energy from oxidizing inorganic substances, such as sulfur
and ammonia.
 Chemoautotrophy is unique to prokaryotes.
 Heterotrophs live on organic compounds produced by other organisms.
 These organisms are the consumers of the biosphere.
 The most obvious type of heterotrophs feeds on other organisms.
 Animals feed this way.
 Other heterotrophs decompose and feed on dead organisms or on organic litter, like
feces and fallen leaves.
 Most fungi and many prokaryotes get their nourishment this way.
 Almost all heterotrophs are completely dependent on photoautotrophs for food and for
oxygen, a by-product of photosynthesis.

Concept 10.1 Photosynthesis converts light energy to the chemical energy of food
 All green parts of a plant have chloroplasts.
 However, the leaves are the major site of photosynthesis for most plants.
 There are about half a million chloroplasts per square millimeter of leaf surface.
 The color of a leaf comes from chlorophyll, the green pigment in the chloroplasts.
 Chlorophyll plays an important role in the absorption of light energy during
Biology Chapter Notes
 Chloroplasts are found mainly in mesophyll cells forming the tissues in the interior of the
 O2 exits and CO2 enters the leaf through microscopic pores called stomata in the leaf.
 Veins deliver water from the roots and carry off sugar from mesophyll cells to
nonphotosynthetic areas of the plant.
 A typical mesophyll cell has 30–40 chloroplasts, each about 2–4 microns by 4–7 microns
 Each chloroplast has two membranes around a central aqueous space, the stroma.
 In the stroma is an elaborate system of interconnected membranous sacs, the thylakoids.
 The interior of the thylakoids forms another compartment, the thylakoid space.
 Thylakoids may be stacked into columns called grana.
 Chlorophyll is located in the thylakoids.
 Photosynthetic prokaryotes lack chloroplasts.
 Their photosynthetic membranes arise from infolded regions of the plasma
membranes, folded in a manner similar to the thylakoid membranes of chloroplasts.
Evidence that chloroplasts split water molecules enabled researchers to track atoms
through photosynthesis.
 Powered by light, the green parts of plants produce organic compounds and O 2 from CO2
and H2O.
 The equation describing the process of photosynthesis is:
 6CO2 + 12H2O + light energy  C6H12O6 + 6O2+ 6H2O
 C6H12O6 is glucose.
 Water appears on both sides of the equation because 12 molecules of water are consumed,
and 6 molecules are newly formed during photosynthesis.
 We can simplify the equation by showing only the net consumption of water:
 6CO2 + 6H2O + light energy  C6H12O6 + 6O2
 The overall chemical change during photosynthesis is the reverse of cellular respiration.
 In its simplest possible form: CO2 + H2O + light energy  [CH2O] + O2
 [CH2O] represents the general formula for a sugar.
 One of the first clues to the mechanism of photosynthesis came from the discovery that
the O2 given off by plants comes from H2O, not CO2.
 Before the 1930s, the prevailing hypothesis was that photosynthesis split carbon
dioxide and then added water to the carbon:
 Step 1: CO2  C + O2
 Step 2: C + H2O  CH2O
 C. B. van Niel challenged this hypothesis.
 In the bacteria that he was studying, hydrogen sulfide (H 2S), not water, is used in
 These bacteria produce yellow globules of sulfur as a waste, rather than oxygen.
 Van Niel proposed this chemical equation for photosynthesis in sulfur bacteria:
 CO2 + 2H2S  [CH2O] + H2O + 2S
 He generalized this idea and applied it to plants, proposing this reaction for their
Biology Chapter Notes
 CO2 + 2H2O  [CH2O] + H2O + O2
 Thus, van Niel hypothesized that plants split water as a source of electrons from hydrogen
atoms, releasing oxygen as a byproduct.
 Other scientists confirmed van Niel’s hypothesis twenty years later.
 They used 18O, a heavy isotope, as a tracer.
 They could label either C18O2 or H218O.
 They found that the 18O label only appeared in the oxygen produced in photosynthesis
when water was the source of the tracer.
 Hydrogen extracted from water is incorporated into sugar, and oxygen is released to the
atmosphere (where it can be used in respiration).
 Photosynthesis is a redox reaction.
 It reverses the direction of electron flow in respiration.
 Water is split and electrons transferred with H+ from water to CO2, reducing it to sugar.
 Because the electrons increase in potential energy as they move from water to sugar,
the process requires energy.
 The energy boost is provided by light.
Here is a preview of the two stages of photosynthesis.
 Photosynthesis is two processes, each with multiple stages.
 The light reactions (photo) convert solar energy to chemical energy.
 The Calvin cycle (synthesis) uses energy from the light reactions to incorporate CO2 from
the atmosphere into sugar.
 In the light reactions, light energy absorbed by chlorophyll in +the thylakoids drives the
transfer of electrons and hydrogen from water to NADP (nicotinamide adenine
dinucleotide phosphate), forming NADPH.
 NADPH, an electron acceptor, provides reducing power via energized electrons to the
Calvin cycle.
 Water is split in the process, and O2 is released as a by-product.
 The light reaction also generates ATP using chemiosmosis, in a process called
 Thus light energy is initially converted to chemical energy in the form of two compounds:
 The Calvin cycle is named for Melvin Calvin who, with his colleagues, worked out many
of its steps in the 1940s.
 The cycle begins with the incorporation of CO2 into organic molecules, a process known
as carbon fixation.
 The fixed carbon is reduced with electrons provided by NADPH.
 ATP from the light reactions also powers parts of the Calvin cycle.
 Thus, it is the Calvin cycle that makes sugar, but only with the help of ATP and NADPH
from the light reactions.
 The metabolic steps of the Calvin cycle are sometimes referred to as the light-independent
reactions, because none of the steps requires light directly.
 Nevertheless, the Calvin cycle in most plants occurs during daylight, because that is when
the light reactions can provide the NADPH and ATP the Calvin cycle requires.
Biology Chapter Notes
 While the light reactions occur at the thylakoids, the Calvin cycle occurs in the stroma.

Concept 10.2 The light reactions convert solar energy to the chemical energy of ATP
 The thylakoids convert light energy into the chemical energy of ATP and NADPH.
 Light is a form of electromagnetic radiation.
 Like other forms of electromagnetic energy, light travels in rhythmic waves.
 The distance between crests of electromagnetic waves is called the wavelength.
 Wavelengths of electromagnetic radiation range from less than a nanometer (gamma
rays) to more than a kilometer (radio waves).
 The entire range of electromagnetic radiation is the electromagnetic spectrum.
 The most important segment for life is a narrow band between 380 to 750 nm, the band of
visible light.
 While light travels as a wave, many of its properties are those of a discrete particle, the
 Photons are not tangible objects, but they do have fixed quantities of energy.
 The amount of energy packaged in a photon is inversely related to its wavelength.
 Photons with shorter wavelengths pack more energy.
 While the sun radiates a full electromagnetic spectrum, the atmosphere selectively screens
out most wavelengths, permitting only visible light to pass in significant quantities.
 Visible light is the radiation that drives photosynthesis.
 When light meets matter, it may be reflected, transmitted, or absorbed.
 Different pigments absorb photons of different wavelengths, and the wavelengths that
are absorbed disappear.
 A leaf looks green because chlorophyll, the dominant pigment, absorbs red and blue
light, while transmitting and reflecting green light.
 A spectrophotometer measures the ability of a pigment to absorb various wavelengths of
 It beams narrow wavelengths of light through a solution containing the pigment and
measures the fraction of light transmitted at each wavelength.
 An absorption spectrum plots a pigment’s light absorption versus wavelength.
 The light reaction can perform work with those wavelengths of light that are absorbed.
 There are several pigments in the thylakoid that differ in their absorption spectra.
 Chlorophyll a, the dominant pigment, absorbs best in the red and violet-blue
wavelengths and least in the green.
 Other pigments with different structures have different absorption spectra.
 Collectively, these photosynthetic pigments determine an overall action spectrum for
 An action spectrum measures changes in some measure of photosynthetic activity (for
example, O2 release) as the wavelength is varied.
 The action spectrum of photosynthesis was first demonstrated in 1883 in an elegant
experiment performed by Thomas Engelmann.

Biology Chapter Notes

 In this experiment, different segments of a filamentous alga were exposed to different
wavelengths of light.
 Areas receiving wavelengths favorable to photosynthesis produced excess O2.
 Engelmann used the abundance of aerobic bacteria that clustered along the alga at
different segments as a measure of O2 production.
 The action spectrum of photosynthesis does not match exactly the absorption spectrum of
any one photosynthetic pigment, including chlorophyll a.
 Only chlorophyll a participates directly in the light reaction, but accessory photosynthetic
pigments absorb light and transfer energy to chlorophyll a.
 Chlorophyll b, with a slightly different structure than chlorophyll a, has a slightly
different absorption spectrum and funnels the energy from these wavelengths to
chlorophyll a.
 Carotenoids can funnel the energy from other wavelengths to chlorophyll a and also
participate in photoprotection against excessive light.
 These compounds absorb and dissipate excessive light energy that would otherwise
damage chlorophyll.
 They also interact with oxygen to form reactive oxidative molecules that could damage
the cell.
 When a molecule absorbs a photon, one of that molecule’s electrons is elevated to an
orbital with more potential energy.
 The electron moves from its ground state to an excited state.
 The only photons that a molecule can absorb are those whose energy matches exactly
the energy difference between the ground state and excited state of this electron.
 Because this energy difference varies among atoms and molecules, a particular
compound absorbs only photons corresponding to specific wavelengths.
 Thus, each pigment has a unique absorption spectrum.
 Excited electrons are unstable.
 Generally, they drop to their ground state in a billionth of a second, releasing heat energy.
 Some pigments, including chlorophyll, can also release a photon of light in a process
called fluorescence.
 If a solution of chlorophyll isolated from chloroplasts is illuminated, it will fluoresce
and give off heat.
 Chlorophyll excited by absorption of light energy produces very different results in an
intact chloroplast than it does in isolation.
 In the thylakoid membrane, chlorophyll is organized along with proteins and smaller
organic molecules into photosystems.
 A photosystem is composed of a reaction center surrounded by a light-harvesting
 Each light-harvesting complex consists of pigment molecules (which may include
chlorophyll a, chlorophyll b, and carotenoid molecules) bound to particular proteins.
 Together, these light-harvesting complexes act like light-gathering “antenna complexes”
for the reaction center.
 When any antenna molecule absorbs a photon, it is transmitted from molecule to molecule
until it reaches a particular chlorophyll a molecule, the reaction center.

Biology Chapter Notes

 At the reaction center is a primary electron acceptor, which accepts an excited electron
from the reaction center chlorophyll a.
 The solar-powered transfer of an electron from a special chlorophyll a molecule to the
primary electron acceptor is the first step of the light reactions.
 Each photosystem—reaction-center chlorophyll and primary electron acceptor surrounded
by an antenna complex—functions in the chloroplast as a light-harvesting unit.
 There are two types of photosystems in the thylakoid membrane.
 Photosystem I (PS I) has a reaction center chlorophyll a that has an absorption peak at
700 nm.
 Photosystem II (PS II) has a reaction center chlorophyll a that has an absorption peak
at 680 nm.
 The differences between these reaction centers (and their absorption spectra) lie not in
the chlorophyll molecules, but in the proteins associated with each reaction center.
 These two photosystems work together to use light energy to generate ATP and
 During the light reactions, there are two possible routes for electron flow: cyclic and
 Noncyclic electron flow, the predominant route, produces both ATP and NADPH.
o Photosystem II absorbs a photon of light. One of the electrons of P680 is excited to a
higher energy state.
o This electron is captured by the primary electron acceptor, leaving the reaction center
o An enzyme extracts electrons from water and supplies them to the oxidized reaction
center. This reaction splits water into two hydrogen ions and an oxygen atom that
combines with another oxygen atom to form O2.
o Photoexcited electrons pass along an electron transport chain before ending up at an
oxidized photosystem I reaction center.
o As these electrons “fall” to a lower energy level, their energy is harnessed to produce
o Meanwhile, light energy has excited an electron of PS I’s P700 reaction center. The
photoexcited electron was captured by PS I’s primary electron acceptor, creating an
electron “hole” in P700. This hole is filled by an electron that reaches the bottom of the
electron transport chain from PS II.
o Photoexcited electrons are passed from PS I’s primary electron acceptor down a
second electron transport chain through the protein ferredoxin (Fd).
o The enzyme NADP+ reductase +
transfers electrons from Fd to NADP+. Two electrons
are required for NADP ’s reduction to NADPH. NADPH will carry the reducing
power of these high-energy electrons to the Calvin cycle.
 The light reactions use the solar power of photons absorbed by both photosystem I and
photosystem II to provide chemical energy in the form of ATP and reducing power in the
form of the electrons carried by NADPH.
 Under certain conditions, photoexcited electrons from photosystem I, but not photosystem
II, can take an alternative pathway, cyclic electron flow.
 Excited electrons cycle from their reaction center to a primary acceptor, along an
electron transport chain, and return to the oxidized P700 chlorophyll.
 As electrons flow along the electron transport chain, they generate ATP by cyclic
 There is no production of NADPH and no release of oxygen.
Biology Chapter Notes
 What is the function of cyclic electron flow?
 Noncyclic electron flow produces ATP and NADPH in roughly equal quantities.
 However, the Calvin cycle consumes more ATP than NADPH.
 Cyclic electron flow allows the chloroplast to generate enough surplus ATP to satisfy the
higher demand for ATP in the Calvin cycle.
 Chloroplasts and mitochondria generate ATP by the same mechanism: chemiosmosis.
 In both organelles, an electron transport chain pumps protons across a membrane as
electrons are passed along a series of increasingly electronegative carriers.
 This transforms redox energy to a proton-motive force in the form of an H+ gradient
across the membrane.
 ATP synthase molecules harness the proton-motive force to generate ATP as H+
diffuses back across the membrane.
 Some of the electron carriers, including the cytochromes, are very similar in chloroplasts
and mitochondria.
 The ATP synthase complexes of the two organelles are also very similar.
 There are differences between oxidative phosphorylation in mitochondria and
photophosphorylation in chloroplasts.
 Mitochondria transfer chemical energy from food molecules to ATP; chloroplasts
transform light energy into the chemical energy of ATP.
 The spatial organization of chemiosmosis also differs in the two organelles.
 The inner membrane of the mitochondrion pumps protons from the mitochondrial matrix
out to the intermembrane space. The thylakoid membrane of the chloroplast pumps
protons from the stroma into the thylakoid space inside the thylakoid.
 The thylakoid membrane makes ATP as the hydrogen ions diffuse down their
concentration gradient from the thylakoid space back to the stroma through ATP synthase
complexes, whose catalytic knobs are on the stroma side of the membrane.
 The proton gradient, or pH gradient, across the thylakoid membrane is substantial.
 When chloroplasts are illuminated, the pH in the thylakoid space drops+ to about 5 and
the pH in the stroma increases to about 8, a thousandfold different in H concentration.
 The light-reaction “machinery” produces ATP and NADPH on the stroma side of the
 Noncyclic electron flow pushes electrons from water, where they have low potential
energy, to NADPH, where they have high potential energy.
 This process also produces ATP and oxygen as a by-product.

Concept 10.3 The Calvin cycle uses ATP and NADPH to convert CO2 to sugar
 The Calvin cycle regenerates its starting material after molecules enter and leave the
 The Calvin cycle is anabolic, using energy to build sugar from smaller molecules.
 Carbon enters the cycle as CO2 and leaves as sugar.
 The cycle spends the energy of ATP and the reducing power of electrons carried by
NADPH to make sugar.

Biology Chapter Notes

 The actual sugar product of the Calvin cycle is not glucose, but a three-carbon sugar,
glyceraldehyde-3-phosphate (G3P).
 Each turn of the Calvin cycle fixes one carbon.
 For the net synthesis of one G3P molecule, the cycle must take place three times, fixing
three molecules of CO2.
 To make one glucose molecule requires six cycles and the fixation of six CO 2 molecules.
 The Calvin cycle has three phases.
Phase 1: Carbon fixation
 In the carbon fixation phase, each CO2 molecule is attached to a five-carbon sugar,
ribulose bisphosphate (RuBP).
 This is catalyzed by RuBP carboxylase or rubisco.
 Rubisco is the most abundant protein in chloroplasts and probably the most abundant
protein on Earth.
 The six-carbon intermediate is unstable and splits in half to form two molecules of 3-
phosphoglycerate for each CO2.
Phase 2: Reduction
 During reduction, each 3-phosphoglycerate receives another phosphate group from ATP
to form 1,3-bisphosphoglycerate.
 A pair of electrons from NADPH reduces each 1,3-bisphosphoglycerate to G3P.
 The electrons reduce a carboxyl group to the aldehyde group of G3P, which stores
more potential energy.
 If our goal was the net production of one G3P, we would start with 3CO 2 (3C) and three
RuBP (15C).
 After fixation and reduction, we would have six molecules of G3P (18C).
 One of these six G3P (3C) is a net gain of carbohydrate.
 This molecule can exit the cycle and be used by the plant cell.
Phase 3: Regeneration
 The other five G3P (15C) remain in the cycle to regenerate three RuBP. In a complex
series of reactions, the carbon skeletons of five molecules of G3P are rearranged by the
last steps of the Calvin cycle to regenerate three molecules of RuBP.
 For the net synthesis of one G3P molecule, the Calvin cycle consumes nine ATP and six
 The light reactions regenerate ATP and NADPH.
 The G3P from the Calvin cycle is the starting material for metabolic pathways that
synthesize other organic compounds, including glucose and other carbohydrates.

Concept 10.4 Alternative mechanisms of carbon fixation have evolved in hot, arid
 One of the major problems facing terrestrial plants is dehydration.
 At times, solutions to this problem require tradeoffs with other metabolic processes,
especially photosynthesis.
Biology Chapter Notes
 The stomata are not only the major route for gas exchange (CO 2 in and O2 out), but also
for the evaporative loss of water.
 On hot, dry days, plants close their stomata to conserve water. This causes problems for
 In most plants (C3 plants), initial fixation of CO2 occurs via rubisco, forming a three-
carbon compound, 3-phosphoglycerate.
 C3 plants include rice, wheat, and soybeans.
 When their stomata partially close on a hot, dry day, CO 2 levels drop as CO2 is consumed
in the Calvin cycle.
 At the same time, O2 levels rise as the light reaction converts light to chemical energy.
 While rubisco normally accepts CO2, when the O2:CO2 ratio increases (on a hot, dry day
with closed stomata), rubisco can add O2 to RuBP.
 When rubisco adds O2 to RuBP, RuBP splits into a three-carbon piece and a two-carbon
piece in a process called photorespiration.
 The two-carbon fragment is exported from the chloroplast and degraded to CO 2 by
mitochondria and peroxisomes.
 Unlike normal respiration, this process produces no ATP.
 In fact, photorespiration consumes ATP.
 Unlike photosynthesis, photorespiration does not produce organic molecules.
 In fact, photorespiration decreases photosynthetic output by siphoning organic
material from the Calvin cycle.
 A hypothesis for the existence of photorespiration is that it is evolutionary baggage.
 When rubisco first evolved, the atmosphere had far less O 2 and more CO2 than it does
 The inability of the active site of rubisco to exclude O 2 would have made little
 Today it does make a difference.
 Photorespiration can drain away as much as 50% of the carbon fixed by the Calvin
cycle on a hot, dry day.
 Certain plant species have evolved alternate modes of carbon fixation to minimize
 C4 plants first fix CO2 in a four-carbon compound.
 Several thousand plants, including sugarcane and corn, use this pathway.
 A unique leaf anatomy is correlated with the mechanism of C4 photosynthesis.
 In C4 plants, there are two distinct types of photosynthetic cells: bundle-sheath cells and
mesophyll cells.
 Bundle-sheath cells are arranged into tightly packed sheaths around the veins of the
 Mesophyll cells are more loosely arranged cells located between the bundle sheath and
the leaf surface.
 The Calvin cycle is confined to the chloroplasts of the bundle-sheath cells.
 However, the cycle is preceded by the incorporation of CO2 into organic molecules in the

Biology Chapter Notes

 The key enzyme, phosphoenolpyruvate carboxylase, adds CO 2 to phosphoenolpyruvate
(PEP) to form oxaloacetate.
 PEP carboxylase has a very high affinity for CO2 and can fix CO2 efficiently when
rubisco cannot (i.e., on hot, dry days when the stomata are closed).
 The mesophyll cells pump these four-carbon compounds into bundle-sheath cells.
 The bundle-sheath cells strip a carbon from the four-carbon compound as CO2, and
return the three-carbon remainder to the mesophyll cells.
 The bundle-sheath cells then use rubisco to start the Calvin cycle with an abundant
supply of CO2.
 In effect, the mesophyll cells pump CO2 into the bundle-sheath cells, keeping CO2 levels
high enough for rubisco to accept CO2 and not O2.
 C4 photosynthesis minimizes photorespiration and enhances sugar production.
 C4 plants thrive in hot regions with intense sunlight.
 A second strategy to minimize photorespiration is found in succulent plants, cacti,
pineapples, and several other plant families.
 These plants are known as CAM plants for crassulacean acid metabolism.
 They open their stomata during the night and close them during the day.
 Temperatures are typically lower at night, and humidity is higher.
 During the night, these plants fix CO2 into a variety of organic acids in mesophyll
 During the day, the light reactions supply ATP and NADPH to the Calvin cycle, and
CO2 is released from the organic acids.
 Both C4 and CAM plants add CO2 into organic intermediates before it enters the Calvin
 In C4 plants, carbon fixation and the Calvin cycle are spatially separated.
 In CAM plants, carbon fixation and the Calvin cycle are temporally separated.
 Both eventually use the Calvin cycle to make sugar from carbon dioxide.
Here is a review of the importance of photosynthesis.
 In photosynthesis, the energy that enters the chloroplasts as sunlight becomes stored as
chemical energy in organic compounds.
 Sugar made in the chloroplasts supplies the entire plant with chemical energy and carbon
skeletons to synthesize all the major organic molecules of cells.
 About 50% of the organic material is consumed as fuel for cellular respiration in plant
 Carbohydrate in the form of the disaccharide sucrose travels via the veins to
nonphotosynthetic cells.
 There, it provides fuel for respiration and the raw materials for anabolic pathways,
including synthesis of proteins and lipids and formation of the extracellular
polysaccharide cellulose.
 Cellulose, the main ingredient of cell walls, is the most abundant organic molecule
in the plant, and probably on the surface of the planet.
 Plants also store excess sugar by synthesis of starch.
 Starch is stored in chloroplasts and in storage cells in roots, tubers, seeds, and fruits.
 Heterotrophs, including humans, may completely or partially consume plants for fuel and
raw materials.
Biology Chapter Notes
 On a global scale, photosynthesis is the most important process on Earth.
 It is responsible for the presence of oxygen in our atmosphere.
 Each year, photosynthesis synthesizes 160 billion metric tons of carbohydrate.

Biology Chapter Notes

Chapter 11 Cell Communication
Chapter Notes

Overview: The Cellular Internet

 Cell-to-cell communication is absolutely essential for multicellular organisms.

 Cells must communicate to coordinate their activities.
 Communication between cells is also important for many unicellular organisms.
 Biologists have discovered universal mechanisms of cellular regulation involving the
same small set of cell-signaling mechanisms.
 The ubiquity of these mechanisms provides additional evidence for the evolutionary
relatedness of all life.
 Cells most often communicate by chemical signals, although signals may take other

Concept 11.1 External signals are converted into responses within the cell
 What messages are passed from cell to cell? How do cells respond to these messages?
 We will first consider communication in microbes, to gain insight into the evolution of
cell signaling.
Cell signaling evolved early in the history of life.
 One topic of cell “conversation” is sex.
 Saccharomyces cerevisiae, the yeast of bread, wine, and beer, identifies potential mates
by chemical signaling.
 There are two sexes, a and , each of which secretes a specific signaling molecule, a
factor and  factor, respectively.
 These factors each bind to receptor proteins on the other mating type.
 Once the mating factors have bound to the receptors, the two cells grow toward each other
and undergo other cellular changes.
 The two cells fuse, or mate, to form an a/ cell containing the genes of both cells.
 The process by which a signal on a cell’s surface is converted into a specific cellular
response is a series of steps called a signal-transduction pathway.
 The molecular details of these pathways are strikingly similar in yeast and animal
cells, even though their last common ancestor lived more than a billion years ago.
 Signaling systems of bacteria and plants also share similarities.
 These similarities suggest that ancestral signaling molecules evolved long ago in
prokaryotes and have since been adopted for new uses by single-celled eukaryotes and
multicellular descendents.
Communicating cells may be close together or far apart.
 Multicellular organisms release signaling molecules that target other cells.
 Cells may communicate by direct contact.
Biology Chapter Notes
 Both animals and plants have cell junctions that connect to the cytoplasm of adjacent
 Signaling substances dissolved in the cytosol can pass freely between adjacent cells.
 Animal cells can communicate by direct contact between membrane-bound cell
surface molecules.
 Such cell-cell recognition is important to such processes as embryonic development
and the immune response.
 In other cases, messenger molecules are secreted by the signaling cell.
 Some transmitting cells release local regulators that influence cells in the local
 One class of local regulators in animals, growth factors, includes compounds that
stimulate nearby target cells to grow and multiply.
 This is an example of paracrine signaling, which occurs when numerous cells
simultaneously receive and respond to growth factors produced by a single cell in their
 In synaptic signaling, a nerve cell produces a neurotransmitter that diffuses across a
synapse to a single cell that is almost touching the sender.
 The neurotransmitter stimulates the target cell.
 The transmission of a signal through the nervous system can also be considered an
example of long-distance signaling.
 Local signaling in plants is not well understood. Because of their cell walls, plants must
have different mechanisms from animals.
 Plants and animals use hormones for long-distance signaling.
 In animals, specialized endocrine cells release hormones into the circulatory system,
by which they travel to target cells in other parts of the body.
 Plant hormones, called growth regulators, may travel in vessels but more often travel
from cell to cell or move through air by diffusion.
 Hormones and local regulators range widely in size and type.
 The plant hormone ethylene (C2H4), which promotes fruit ripening and regulates
growth, is a hydrocarbon of only six atoms, capable of passing through cell walls.
 Insulin, which regulates blood sugar levels in mammals, is a protein with thousands of
 What happens when a cell encounters a signal?
 The signal must be recognized by a specific receptor molecule, and the information it
carries must be changed into another form, or transduced, inside the cell before the
cell can respond.
The three stages of cell signaling are reception, transduction, and response.
 E. W. Sutherland and his colleagues pioneered our understanding of cell signaling.
 Their work investigated how the animal hormone epinephrine stimulates breakdown of
the storage polysaccharide glycogen in liver and skeletal muscle.
 Breakdown of glycogen releases glucose derivatives that can be used for fuel in
glycolysis or released as glucose in the blood for fuel elsewhere.
 Thus one effect of epinephrine, which is released from the adrenal gland during times
of physical or mental stress, is mobilization of fuel reserves.
 Sutherland’s research team discovered that epinephrine activated a cytosolic enzyme,
glycogen phosphorylase.
Biology Chapter Notes
 However, epinephrine did not activate the phosphorylase directly in vitro but could
only act via intact cells.
 Therefore, there must be an intermediate step or steps occurring inside the cell.
 The plasma membrane must be involved in transmitting the epinephrine signal.
 The process involves three stages: reception, transduction, and response.
 In reception, a chemical signal binds to a cellular protein, typically at the cell’s
surface or inside the cell.
 In transduction, binding leads to a change in the receptor that triggers a series of
changes in a series of different molecules along a signal-transduction pathway. The
molecules in the pathway are called relay molecules.
 In response, the transduced signal triggers a specific cellular activity.

Concept 11.2 Reception: A signal molecule binds to a receptor protein, causing it to

change shape
 The cell targeted by a particular chemical signal has a receptor protein on or in the target
cell that recognizes the signal molecule.
 Recognition occurs when the signal binds to a specific site on the receptor that is
complementary in shape to the signal.
 The signal molecule behaves as a ligand, a small molecule that binds with specificity to a
larger molecule.
 Ligand binding causes the receptor protein to undergo a change in shape.
 This may activate the receptor so that it can interact with other molecules.
 For other receptors, this causes aggregation of receptor molecules, leading to further
molecular events inside the cell.
 Most signal receptors are plasma membrane proteins, whose ligands are large water-
soluble molecules that are too large to cross the plasma membrane.
Some receptor proteins are intracellular.
 Some signal receptors are dissolved in the cytosol or nucleus of target cells.
 To reach these receptors, the signals pass through the target cell’s plasma membrane.
 Such chemical messengers are either hydrophobic enough or small enough to cross the
phospholipid interior of the plasma membrane.
 Hydrophobic messengers include the steroid and thyroid hormones of animals.
 Nitric oxide (NO) is a gas whose small size allows it to pass between membrane
 Testosterone is secreted by the testis and travels through the blood to enter cells
throughout the body.
 The cytosol of target cells contains receptor molecules that bind testosterone,
activating the receptor.
 These activated proteins enter the nucleus and turn on specific genes that control male
sex characteristics.
 How does the activated hormone-receptor complex turn on genes?
 These activated proteins act as transcription factors.

Biology Chapter Notes

 Transcription factors control which genes are turned on—that is, which genes are
transcribed into messenger RNA.
 mRNA molecules leave the nucleus and carry information that directs the synthesis
(translation) of specific proteins at the ribosome.
 Other intracellular receptors (such as thyroid hormone receptors) are found in the nucleus
and bind to the signal molecules there.
Most signal receptors are plasma membrane proteins.
 Most signal molecules are water-soluble and too large to pass through the plasma
 They influence cell activities by binding to receptor proteins on the plasma membrane.
 Binding leads to changes in the shape of the receptor or to the aggregation of receptors.
 These cause changes in the intracellular environment.
 There are three major types of membrane receptors: G-protein-linked receptors, receptor
tyrosine kinases, and ion-channel receptors.
 A G-protein-linked receptor consists of a receptor protein associated with a G protein on
the cytoplasmic side.
 Seven alpha helices span the membrane.
 G-protein-linked receptors bind many different signal molecules, including yeast
mating factors, epinephrine and many other hormones, and neurotransmitters.
 The G protein acts as an on/off switch.
 If GDP is bound to the G protein, the G protein is inactive.
 When the appropriate signal molecule binds to the extracellular side of the receptor,
the G protein binds GTP (instead of GDP) and becomes active.
 The activated G protein dissociates from the receptor and diffuses along the
membrane, where it binds to an enzyme, altering its activity.
 The activated enzyme triggers the next step in a pathway leading to a cellular response.
 The G protein can also act as a GTPase enzyme to hydrolyze GTP to GDP.
 This change turns the G protein off.
 Now inactive, the G protein leaves the enzyme, which returns to its original state.
 The whole system can be shut down quickly when the extracellular signal molecule is no
longer present.
 G-protein receptor systems are extremely widespread and diverse in their functions.
 They play important roles during embryonic development.
 Vision and smell in humans depend on these proteins.
 Similarities among G proteins and G-protein-linked receptors of modern organisms
suggest that this signaling system evolved very early.
 Several human diseases involve G-protein systems.
 Bacterial infections causing cholera and botulism interfere with G-protein function.
 The tyrosine-kinase receptor system is especially effective when the cell needs to trigger
several signal transduction pathways and cellular responses at once.
 This system helps the cell regulate and coordinate many aspects of cell growth and

Biology Chapter Notes

 The tyrosine-kinase receptor belongs to a major class of plasma membrane receptors that
have enzymatic activity.
 A kinase is an enzyme that catalyzes the transfer of phosphate groups.
 The cytoplasmic side of these receptors functions as a tyrosine kinase, transferring a
phosphate group from ATP to tyrosine on a substrate protein.
 An individual tyrosine-kinase receptor consists of several parts:
 An extracellular signal-binding site.
 A single alpha helix spanning the membrane.
 An intracellular tail with several tyrosines.
 The signal molecule binds to an individual receptor.
 Ligands bind to two receptors, causing the two receptors to aggregate and form a
 This dimerization activates the tyrosine-kinase section of the receptors, each of which
then adds phosphate from ATP to the tyrosine tail of the other polypeptide.
 The fully activated receptor proteins activate a variety of specific relay proteins that bind
to specific phosphorylated tyrosine molecules.
 One tyrosine-kinase receptor dimer may activate ten or more different intracellular
proteins simultaneously.
 These activated relay proteins trigger many different transduction pathways and
 A ligand-gated ion channel is a type of membrane receptor that can act as a gate when
the receptor changes shape.
 When a signal molecule binds as a ligand to the receptor protein, the gate opens to allow
the flow of specific ions, such as Na+ or Ca2+, through a channel in the receptor.
 Binding by a ligand to the extracellular side changes the protein’s shape and opens the
 When the ligand dissociates from the receptor protein, the channel closes.
 The change in ion concentration within the cell may directly affect the activity of the cell.
 Ligand-gated ion channels are very important in the nervous system.
 For example, neurotransmitter molecules released at a synapse between two neurons
bind as ligands to ion channels on the receiving cell, causing the channels to open.
 Ions flow in and trigger an electrical signal that propagates down the length of the
receiving cell.
 Some gated ion channels respond to electrical signals, instead of ligands.

Concept 11.3 Transduction: Cascades of molecular interactions relay signals from

receptors to target molecules in the cell
 The transduction stage of signaling is usually a multistep pathway.
 These pathways often greatly amplify the signal.
 If some molecules in a pathway transmit a signal to multiple molecules of the next
component in the series, the result can be large numbers of activated molecules at the
end of the pathway.
 A small number of signal molecules can produce a large cellular response.
Biology Chapter Notes
 Also, multistep pathways provide more opportunities for coordination and regulation than
do simpler systems.
Pathways relay signals from receptors to cellular responses.
 Signal-transduction pathways act like falling dominoes.
 The signal-activated receptor activates another protein, which activates another, and so
on, until the protein that produces the final cellular response is activated.
 The relay molecules that relay a signal from receptor to response are mostly proteins.
 The interaction of proteins is a major theme of cell signaling.
 Protein interaction is a unifying theme of all cellular regulation.
 The original signal molecule is not passed along the pathway and may not even enter the
 It passes on information.
 At each step, the signal is transduced into a different form, often by a conformational
change in a protein.
 The conformational change is often brought about by phosphorylation.
Protein phosphorylation, a common mode of regulation in cells, is a major mechanism of
signal transduction.
 The phosphorylation of proteins by a specific enzyme (a protein kinase) is a widespread
cellular mechanism for regulating protein activity.
 Most protein kinases act on other substrate proteins, unlike tyrosine kinases that act on
 Most phosphorylation occurs at either serine or threonine amino acids of the substrate
protein (unlike tyrosine phosphorylation in tyrosine kinases).
 Many of the relay molecules in a signal-transduction pathway are protein kinases that act
on other protein kinases to create a “phosphorylation cascade.”
 Each protein phosphorylation leads to a conformational change because of the interaction
between the newly added phosphate group and charged or polar amino acids on the
 Phosphorylation of a protein typically converts it from an inactive form to an active form.
 Rarely, phosphorylation inactivates protein activity.
 A single cell may have hundreds of different protein kinases, each specific for a different
substrate protein.
 Fully 2% of our genes are thought to code for protein kinases.
 Together, they regulate a large proportion of the thousands of cell proteins.
 Abnormal activity of protein kinases can cause abnormal cell growth and may contribute
to the development of cancer.
 The responsibility for turning off a signal-transduction pathway belongs to protein
 These enzymes rapidly remove phosphate groups from proteins, a process called
 Phosphatases also make the protein kinases available for reuse, enabling the cell to
respond again to a signal.
 At any given moment, the activity of a protein regulated by phosphorylation depends on
the balance of active kinase molecules and active phosphatase molecules.
Biology Chapter Notes
 When the extracellular signal molecule is absent, active phosphatase molecules
predominate, and the signaling pathway and cellular response are shut down.
 The phosphorylation/dephosphorylation system acts as a molecular switch in the cell,
turning activities on and off as required.
Certain signal molecules and ions are key components of signaling pathways (second
 Many signaling pathways involve small, water-soluble, nonprotein molecules or ions
called second messengers.
 These molecules rapidly diffuse throughout the cell.
 Second messengers participate in pathways initiated by both G-protein-linked receptors
and tyrosine-kinase receptors.
 Two of the most widely used second messengers are cyclic AMP and Ca2+.
 Once Sutherland knew that epinephrine caused glycogen breakdown without entering the
cell, he looked for a second messenger inside the cell.
 Binding by epinephrine leads to increases in the cytosolic concentration of cyclic AMP,
or cAMP.
 This occurs because the activated receptor activates adenylyl cyclase, which converts
ATP to cAMP.
 The normal cellular concentration of cAMP can be boosted twentyfold within seconds.
 cAMP is short-lived, as phosphodiesterase converts it to AMP.
 Another surge of epinephrine is needed to reboost the cytosolic concentration of
 Caffeine-containing beverages such as coffee provide an artificial way to keep the body
 Caffeine blocks the conversion of cAMP to AMP, maintaining the system in a state of
activation in the absence of epinephrine.
 Many hormones and other signal molecules trigger the formation of cAMP.
 G-protein-linked receptors, G proteins, and protein kinases are other components of
cAMP pathways.
 cAMP diffuses through the cell and activates a serine/threonine kinase called protein
kinase A.
 The activated kinase phosphorylates various other proteins.
 Regulation of cell metabolism is also provided by G-protein systems that inhibit adenylyl
 These use a different signal molecule to activate a different receptor that activates an
inhibitory G protein.
 Certain microbes cause disease by disrupting G-protein signaling pathways.
 The cholera bacterium, Vibrio cholerae, may be present in water contaminated with
human feces.
 This bacterium colonizes the small intestine and produces a toxin that modifies a G
protein that regulates salt and water secretion.
 The modified G protein is unable to hydrolyze GTP to GDP and remains stuck in its
active form, continuously stimulating adenylyl cyclase to make cAMP.
 The resulting high concentration of cAMP causes the intestinal cells to secrete large
amounts of water and salts into the intestines, leading to profuse diarrhea and death
from loss of water and salts.
Biology Chapter Notes
 Treatments for certain human conditions involve signaling pathways.
 One pathway uses cyclic GMP, or cGMP, as a signaling molecule. Its effects include
the relaxation of smooth muscle cells in artery walls.
 A compound was developed to treat chest pains. This compound inhibits the hydrolysis
of cGMP to GMP, prolonging the signal and increasing blood flow to the heart muscle.
 Under the trade name Viagra, this compound is now widely used as a treatment for
erectile dysfunction. Viagra causes dilation of blood vessels, allowing increased blood
flow to the penis.
 Many signal molecules in animals induce responses in their target cells via signal-
transduction pathways that increase the cytosolic concentration of Ca 2+.
 In animal cells, increases in Ca2+ may cause contraction of muscle cells, secretion of
certain substances, and cell division.
 In plant cells, increases in Ca2+ trigger responses such as the pathway for greening in
response to light.
 Cells use Ca2+ as a second messenger in both G-protein pathways and tyrosine-kinase
 The Ca2+ concentration in the cytosol is typically much lower than that outside the cell,
often by a factor of 10,000 or more.
 Various protein pumps transport Ca2+ outside the cell or into the endoplasmic
reticulum or other organelles.
 As a result, the concentration of Ca2+ in the ER is usually much higher than the
concentration in the cytosol.
 Because cytosolic Ca2+ is so low, small 2+ changes in the absolute numbers of ions causes a
relatively large percentage change in Ca concentration.
 Signal-transduction pathways trigger the release of Ca2+ from the cell’s ER.
 The pathways leading to release involve still other second messengers, diacylglycerol
(DAG) and inositol trisphosphate (IP3).
 DAG and IP3 are created when a phospholipase cleaves membrane phospholipid PIP 2.
 The phospholipase may be activated by a G protein or by a tyrosine-kinase receptor.
 IP3 activates a gated-calcium channel, releasing Ca2+ from the ER.
 Calcium ions activate the next protein in a signal-transduction pathway.

Concept 11.4 Response: Cell signaling leads to regulation of cytoplasmic activities or

 Ultimately, a signal-transduction pathway leads to the regulation of one or more cellular
 This may be the opening or closing of an ion channel or a change in cell metabolism.
 For example, epinephrine helps regulate cellular energy metabolism by activating
enzymes that catalyze the breakdown of glycogen.
 The stimulation of glycogen breakdown by epinephrine involves a G-protein-linked
receptor, a G protein, adenylyl cyclase, cAMP, and several protein kinases before
glycogen phosphorylase is activated.
 Other signaling pathways do not regulate the activity of enzymes but the synthesis of
enzymes or other proteins.

Biology Chapter Notes

 Activated receptors may act as transcription factors that turn specific genes on or off in
the nucleus.
Elaborate pathways amplify and specify the cell’s response to signals.
 Signaling pathways with multiple steps have two benefits.
o They amplify the response to a signal.
o They contribute to the specificity of the response.
 At each catalytic step in a cascade, the number of activated products is much greater than
in the preceding step.
 In the epinephrine-triggered pathway, binding by a small number of epinephrine
molecules can lead to the release of hundreds of millions of glucose molecules.
 Various types of cells may receive the same signal but produce very different responses.
 For example, epinephrine triggers liver or striated muscle cells to break down
glycogen, but stimulates cardiac muscle cells to contract, leading to a rapid heartbeat.
 The explanation for this specificity is that different kinds of cells have different
collections of proteins.
 The response of a particular cell to a signal depends on its particular collection of
receptor proteins, relay proteins, and proteins needed to carry out the response.
 Two cells that respond differently to the same signal differ in one or more of the
proteins that handle and respond to the signal.
 A signal may trigger a single pathway in one cell but trigger a branched pathway in
 Two pathways may converge to modulate a single response.
 Branching of pathways and interactions between pathways are important for regulating
and coordinating a cell’s response to incoming information.
 Rather than relying on diffusion of large relay molecules such as proteins, many signal
pathways are linked together physically by scaffolding proteins.
 Scaffolding proteins may themselves be relay proteins to which several other relay
proteins attach.
 This hardwiring enhances the speed, accuracy, and efficiency of signal transfer
between cells.
 The importance of relay proteins that serve as branch or intersection points in signaling
pathways is underscored when these proteins are defective or missing.
 The inherited disorder Wiskott-Aldrich syndrome (WAS) is caused by the absence of a
single relay protein.
 Symptoms include abnormal bleeding, eczema, and a predisposition to infections and
leukemia, due largely to the absence of the protein in the cells of the immune system.
 The WAS protein is located just beneath the cell surface, where it interacts with the
microfilaments of the cytoskeleton and with several signaling pathways, including
those that regulate immune cell proliferation.
 When the WAS protein is absent, the cytoskeleton is not properly organized and
signaling pathways are disrupted.
 As important as activating mechanisms are inactivation mechanisms.
 For a cell to remain alert and capable of responding to incoming signals, each
molecular change in its signaling pathways must last only a short time.

Biology Chapter Notes

 If signaling pathway components become locked into one state, whether active or
inactive, the proper function of the cell can be disrupted.
 Binding of signal molecules to receptors must be reversible, allowing the receptors to
return to their inactive state when the signal is released.
 Similarly, activated signals (cAMP and phosphorylated proteins) must be inactivated
by appropriate enzymes to prepare the cell for a fresh signal.

Biology Chapter Notes

Chapter 12 The Cell Cycle
Chapter Notes

Overview: The Key Roles of Cell Division

 The ability of organisms to reproduce their kind is the one characteristic that best
distinguishes living things from nonliving matter.
 The continuity of life is based on the reproduction of cells, or cell division.
Cell division functions in reproduction, growth, and repair.
 The division of a unicellular organism reproduces an entire organism, increasing the
 Cell division on a larger scale can produce progeny for some multicellular organisms.
 This includes organisms that can grow by cuttings.
 Cell division enables a multicellular organism to develop from a single fertilized egg or
 In a multicellular organism, cell division functions to repair and renew cells that die from
normal wear and tear or accidents.
 Cell division is part of the cell cycle, the life of a cell from its origin in the division of a
parent cell until its own division into two.

Concept 12.1 Cell division results in genetically identical daughter cells

 Cell division requires the distribution of identical genetic material—DNA—to two
daughter cells.
 What is remarkable is the fidelity with which DNA is passed along, without dilution, from
one generation to the next.
 A dividing cell duplicates its DNA, allocates the two copies to opposite ends of the cell,
and then splits into two daughter cells.
 A cell’s genetic information, packaged as DNA, is called its genome.
 In prokaryotes, the genome is often a single long DNA molecule.
 In eukaryotes, the genome consists of several DNA molecules.
 A human cell must duplicate about 2 m of DNA and separate the two copies such that
each daughter cell ends up with a complete genome.
 DNA molecules are packaged into chromosomes.
 Every eukaryotic species has a characteristic number of chromosomes in each cell
 Human somatic cells (body cells) have 46 chromosomes, made up of two sets of 23
(one from each parent).
 Human gametes (sperm or eggs) have one set of 23 chromosomes, half the number
in a somatic cell.
 Eukaryotic chromosomes are made of chromatin, a complex of DNA and associated
Biology Chapter Notes
 Each single chromosome contains one long, linear DNA molecule carrying hundreds
or thousands of genes, the units that specify an organism’s inherited traits.
 The associated proteins maintain the structure of the chromosome and help control gene
 When a cell is not dividing, each chromosome is in the form of a long, thin chromatin
 Before cell division, chromatin condenses, coiling and folding to make a smaller package.
 Each duplicated chromosome consists of two sister chromatids, which contain identical
copies of the chromosome’s DNA.
 The chromatids are initially attached by adhesive proteins along their lengths.
 As the chromosomes condense, the region where the chromatids connect shrinks to a
narrow area, the centromere.
 Later in cell division, the sister chromatids are pulled apart and repackaged into two new
nuclei at opposite ends of the parent cell.
 Once the sister chromatids separate, they are considered individual chromosomes.
 Mitosis, the formation of the two daughter nuclei, is usually followed by division of the
cytoplasm, cytokinesis.
 These processes start with one cell and produce two cells that are genetically identical to
the original parent cell.
 Each of us inherited 23 chromosomes from each parent: one set in an egg and one set
in sperm.
 The fertilized egg, or zygote, underwent cycles of mitosis and cytokinesis to produce a
fully developed multicellular human made up of 200 trillion somatic cells.
 These processes continue every day to replace dead and damaged cells.
 Essentially, these processes produce clones—cells with identical genetic information.
 In contrast, gametes (eggs or sperm) are produced only in gonads (ovaries or testes) by a
variation of cell division called meiosis.
 Meiosis yields four nonidentical daughter cells, each with half the chromosomes of the
 In humans, meiosis reduces the number of chromosomes from 46 to 23.
 Fertilization fuses two gametes together and doubles the number of chromosomes to
46 again.

Concept 12.2 The mitotic phase alternates with interphase in the cell cycle
 The mitotic (M) phase of the cell cycle alternates with the much longer interphase.
 The M phase includes mitosis and cytokinesis.
 Interphase accounts for 90% of the cell cycle.
 During interphase, the cell grows by producing proteins and cytoplasmic organelles,
copies its chromosomes, and prepares for cell division.
 Interphase has three subphases: the G1 phase (“first gap”), the S phase (“synthesis”), and
the G2 phase (“second gap”).
 During all three subphases, the cell grows by producing proteins and cytoplasmic
organelles such as mitochondria and endoplasmic reticulum.
 However, chromosomes are duplicated only during the S phase.
Biology Chapter Notes
 The daughter cells may then repeat the cycle.
 A typical human cell might divide once every 24 hours.
 Of this time, the M phase would last less than an hour, while the S phase might take
10–12 hours, or half the cycle.
 The rest of the time would be divided between the G1 and G2 phases.
 The G1 phase varies most in length from cell to cell.
 Mitosis is a continuum of changes.
 For convenience, mitosis is usually broken into five subphases: prophase,
prometaphase, metaphase, anaphase, and telophase.
 In late interphase, the chromosomes have been duplicated but are not condensed.
 A nuclear membrane bounds the nucleus, which contains one or more nucleoli.
 The centrosome has replicated to form two centrosomes.
 In animal cells, each centrosome features two centrioles.
 In prophase, the chromosomes are tightly coiled, with sister chromatids joined together.
 The nucleoli disappear.
 The mitotic spindle begins to form.
 It is composed of centrosomes and the microtubules that extend from them.
 The radial arrays of shorter microtubules that extend from the centrosomes are called
 The centrosomes move away from each other, apparently propelled by lengthening
 During prometaphase, the nuclear envelope fragments, and microtubules from the spindle
interact with the condensed chromosomes.
 Each of the two chromatids of a chromosome has a kinetochore, a specialized protein
structure located at the centromere.
 Kinetochore microtubules from each pole attach to one of two kinetochores.
 Nonkinetochore microtubules interact with those from opposite ends of the spindle.
 The spindle fibers push the sister chromatids until they are all arranged at the metaphase
plate, an imaginary plane equidistant from the poles, defining metaphase.
 At anaphase, the centromeres divide, separating the sister chromatids.
 Each is now pulled toward the pole to which it is attached by spindle fibers.
 By the end, the two poles have equivalent collections of chromosomes.
 At telophase, daughter nuclei begin to form at the two poles.
 Nuclear envelopes arise from the fragments of the parent cell’s nuclear envelope and
other portions of the endomembrane system.
 The chromosomes become less tightly coiled.
 Cytokinesis, division of the cytoplasm, is usually well underway by late telophase.
 In animal cells, cytokinesis involves the formation of a cleavage furrow, which pinches
the cell in two.
 In plant cells, vesicles derived from the Golgi apparatus produce a cell plate at the
middle of the cell.
The mitotic spindle distributes chromosomes to daughter cells: a closer look.

Biology Chapter Notes

 The mitotic spindle, fibers composed of microtubules and associated proteins, is a major
driving force in mitosis.
 As the spindle assembles during prophase, the elements come from partial disassembly of
the cytoskeleton.
 The spindle fibers elongate by incorporating more subunits of the protein tubulin.
 Assembly of the spindle microtubules starts in the centrosome.
 The centrosome (microtubule-organizing center) is a nonmembranous organelle that
organizes the cell’s microtubules.
 In animal cells, the centrosome has a pair of centrioles at the center, but the centrioles
are not essential for cell division.
 During interphase, the single centrosome replicates to form two centrosomes.
 As mitosis starts, the two centrosomes are located near the nucleus.
 As the spindle microtubules grow from them, the centrioles are pushed apart.
 By the end of prometaphase, they are at opposite ends of the cell.
 An aster, a radial array of short microtubules, extends from each centrosome.
 The spindle includes the centrosomes, the spindle microtubules, and the asters.
 Each sister chromatid has a kinetochore of proteins and chromosomal DNA at the
 The kinetochores of the joined sister chromatids face in opposite directions.
 During prometaphase, some spindle microtubules (called kinetochore microtubules) attach
to the kinetochores.
 When a chromosome’s kinetochore is “captured” by microtubules, the chromosome
moves toward the pole from which those microtubules come.
 When microtubules attach to the other pole, this movement stops and a tug-of-war ensues.
 Eventually, the chromosome settles midway between the two poles of the cell, on the
metaphase plate.
 Nonkinetochore microtubules from opposite poles overlap and interact with each other.
 By metaphase, the microtubules of the asters have grown and are in contact with the
plasma membrane.
 The spindle is now complete.
 Anaphase commences when the proteins holding the sister chromatids together are
 Once the chromosomes are separate, full-fledged chromosomes, they move toward
opposite poles of the cell.
 How do the kinetochore microtubules function into the poleward movement of
 One hypothesis is that the chromosomes are “reeled in” by the shortening of microtubules
at the spindle poles.
 Experimental evidence supports the hypothesis that motor proteins on the kinetochore
“walk” the attached chromosome along the microtubule toward the nearest pole.
 Meanwhile, the excess microtubule sections depolymerize at their kinetochore ends.
 What is the function of the nonkinetochore microtubules?

Biology Chapter Notes

 Nonkinetochore microtubules are responsible for lengthening the cell along the axis
defined by the poles.
 These microtubules interdigitate and overlap across the metaphase plate.
 During anaphase, the area of overlap is reduced as motor proteins attached to the
microtubules walk them away from one another, using energy from ATP.
 As microtubules push apart, the microtubules lengthen by the addition of new tubulin
monomers to their overlapping ends, allowing continued overlap.
Cytokinesis divides the cytoplasm: a closer look.
 Cytokinesis, division of the cytoplasm, typically follows mitosis.
 In animal cells, cytokinesis occurs by a process called cleavage.
 The first sign of cleavage is the appearance of a cleavage furrow in the cell surface near
the old metaphase plate.
 On the cytoplasmic side of the cleavage furrow is a contractile ring of actin
microfilaments associated with molecules of the motor protein myosin.
 Contraction of the ring pinches the cell in two.
 Cytokinesis in plants, which have cell walls, involves a completely different mechanism.
 During telophase, vesicles from the Golgi coalesce at the metaphase plate, forming a cell
 The plate enlarges until its membranes fuse with the plasma membrane at the
 The contents of the vesicles form new cell wall material between the daughter cells.
Mitosis in eukaryotes may have evolved from binary fission in bacteria.
 Prokaryotes reproduce by binary fission, not mitosis.
 Most bacterial genes are located on a single bacterial chromosome that consists of a
circular DNA molecule and associated proteins.
 While bacteria are smaller and simpler than eukaryotic cells, they still have large amounts
of DNA that must be copied and distributed equally to two daughter cells.
 The circular bacterial chromosome is highly folded and coiled in the cell.
 In binary fission, chromosome replication begins at one point in the circular chromosome,
the origin of replication site, producing two origins.
 As the chromosome continues to replicate, one origin moves toward each end of the
 While the chromosome is replicating, the cell elongates.
 When replication is complete, its plasma membrane grows inward to divide the parent
cell into two daughter cells, each with a complete genome.
 Researchers have developed methods to allow them to observe the movement of bacterial
 The movement is similar to the poleward movements of the centromere regions of
eukaryotic chromosomes.
 However, bacterial chromosomes lack visible mitotic spindles or even microtubules.
 The mechanism behind the movement of the bacterial chromosome is becoming clearer
but is still not fully understood.
 Several proteins have been identified and play important roles.
Biology Chapter Notes
 How did mitosis evolve?
 There is evidence that mitosis had its origins in bacterial binary fission.
 Some of the proteins involved in binary fission are related to eukaryotic proteins.
 Two of these are related to eukaryotic tubulin and actin proteins.
 As eukaryotes evolved, the ancestral process of binary fission gave rise to mitosis.
 Possible intermediate evolutionary steps are seen in the division of two types of
unicellular algae.
 In dinoflagellates, replicated chromosomes are attached to the nuclear envelope.
 In diatoms, the spindle develops within the nucleus.
 In most eukaryotic cells, the nuclear envelope breaks down and a spindle separates the

Concept 12.3 The cell cycle is regulated by a molecular control system

 The timing and rates of cell division in different parts of an animal or plant are crucial for
normal growth, development, and maintenance.
 The frequency of cell division varies with cell type.
 Some human cells divide frequently throughout life (skin cells).
 Others have the ability to divide, but keep it in reserve (liver cells).
 Mature nerve and muscle cells do not appear to divide at all after maturity.
 Investigation of the molecular mechanisms regulating these differences provide important
insights into the operation of normal cells, and may also explain cancer cells escape
Cytoplasmic signals drive the cell cycle.
 The cell cycle appears to be driven by specific chemical signals present in the cytoplasm.
 Some of the initial evidence for this hypothesis came from experiments in which cultured
mammalian cells at different phases of the cell cycle were fused to form a single cell with
two nuclei.
 Fusion of an S phase cell and a G1 phase cell induces the G1 nucleus to start S phase.
 This suggests that chemicals present in the S phase nucleus stimulated the fused
 Fusion of a cell in mitosis (M phase) with one in interphase (even G 1 phase) induces
the second cell to enter mitosis.
 The sequential events of the cell cycle are directed by a distinct cell cycle control system.
 Cyclically operating molecules trigger and coordinate key events in the cell cycle.
 The control cycle has a built-in clock, but it is also regulated by external adjustments
and internal controls.
 A checkpoint in the cell cycle is a critical control point where stop and go-ahead signals
regulate the cycle.
 The signals are transmitted within the cell by signal transduction pathways.
 Animal cells generally have built-in stop signals that halt the cell cycle at checkpoints
until overridden by go-ahead signals.
 Many signals registered at checkpoints come from cellular surveillance mechanisms.
 These indicate whether key cellular processes have been completed correctly.
Biology Chapter Notes
 Checkpoints also register signals from outside the cell.
 Three major checkpoints are found in the G1, G2, and M phases.
 For many cells, the G1 checkpoint, the “restriction point” in mammalian cells, is the most
 If the cell receives a go-ahead signal at the G1 checkpoint, it usually completes the cell
cycle and divides.
 If it does not receive a go-ahead signal, the cell exits the cycle and switches to a
nondividing state, the G0 phase.
 Most cells in the human body are in this phase.
 Liver cells can be “called back” to the cell cycle by external cues, such as growth
factors released during injury.
 Highly specialized nerve and muscle cells never divide.
 Rhythmic fluctuations in the abundance and activity of cell cycle control molecules pace
the events of the cell cycle.
 These regulatory molecules include protein kinases that activate or deactivate other
proteins by phosphorylating them.
 These kinases are present in constant amounts but require attachment of a second protein,
a cyclin, to become activated.
 Levels of cyclin proteins fluctuate cyclically.
 Because of the requirement for binding of a cyclin, the kinases are called cyclin-
dependent kinases, or Cdks.
 Cyclin levels rise sharply throughout interphase, and then fall abruptly during mitosis.
 Peaks in the activity of one cyclin-Cdk complex, MPF, correspond to peaks in cyclin
 MPF (“maturation-promoting factor” or “M-phase-promoting-factor”) triggers the cell’s
passage past the G2 checkpoint to the M phase.
 MPF promotes mitosis by phosphorylating a variety of other protein kinases.
 MPF stimulates fragmentation of the nuclear envelope by phosphorylation of various
proteins of the nuclear lamina.
 It also triggers the breakdown of cyclin, dropping cyclin and MPF levels during
mitosis and inactivating MPF.
 The noncyclin part of MPF, the Cdk, persists in the cell in inactive form until it
associates with new cyclin molecules synthesized during the S and G2 phases of the
next round of the cycle.
 At least three Cdk proteins and several cyclins regulate the key G1 checkpoint.
 Similar mechanisms are also involved in driving the cell cycle past the M phase
Internal and external cues help regulate the cell cycle.
 While research scientists know that active Cdks function by phosphorylating proteins, the
identity of all these proteins is still under investigation.
 Scientists do not yet know what Cdks actually do in most cases.
 Some steps in the signaling pathways that regulate the cell cycle are clear.
 Some signals originate inside the cell, others outside.

Biology Chapter Notes

 The M phase checkpoint ensures that all the chromosomes are properly attached to the
spindle at the metaphase plate before anaphase.
 This ensures that daughter cells do not end up with missing or extra chromosomes.
 A signal to delay anaphase originates at kinetochores that have not yet attached to spindle
 This keeps the anaphase-promoting complex (APC) in an inactive state.
 When all kinetochores are attached, the APC activates, triggering breakdown of cyclin
and inactivation of proteins holding sister chromatids together.
 A variety of external chemical and physical factors can influence cell division.
 For example, cells fail to divide if an essential nutrient is left out of the culture
 Particularly important for mammalian cells are growth factors, proteins released by one
group of cells that stimulate other cells to divide.
 For example, platelet-derived growth factors (PDGF), produced by platelet blood
cells, bind to tyrosine-kinase receptors of fibroblasts, a type of connective tissue cell.
 This triggers a signal-transduction pathway that allows cells to pass the G 1 checkpoint
and divide.
 Each cell type probably responds specifically to a certain growth factor or combination of
 The role of PDGF is easily seen in cell culture.
 Fibroblasts in culture will only divide in the presence of a medium that also contains
 In a living organism, platelets release PDGF in the vicinity of an injury.
 The resulting proliferation of fibroblasts helps heal the wound.
 At least 50 different growth factors can trigger specific cells to divide.
 The effect of an external physical factor on cell division can be seen in density-
dependent inhibition of cell division.
 Cultured cells normally divide until they form a single layer on the inner surface of the
culture container.
 If a gap is created, the cells will grow to fill the gap.
 At high densities, the amount of growth factors and nutrients is insufficient to allow
continued cell growth.
 Most animal cells also exhibit anchorage dependence for cell division.
 To divide, they must be anchored to a substratum, typically the extracellular matrix of
a tissue.
 Control appears to be mediated by pathways involving plasma membrane proteins and
elements of the cytoskeleton linked to them.
 Cancer cells exhibit neither density-dependent inhibition nor anchorage dependence.
Cancer cells have escaped from cell cycle controls.
 Cancer cells divide excessively and invade other tissues because they are free of the
body’s control mechanisms.
 Cancer cells do not stop dividing when growth factors are depleted.
 This is either because a cancer cell manufactures its own growth factors, has an
abnormality in the signaling pathway, or has an abnormal cell cycle control system.
Biology Chapter Notes
 If and when cancer cells stop dividing, they do so at random points, not at the normal
checkpoints in the cell cycle.
 Cancer cells may divide indefinitely if they have a continual supply of nutrients.
 In contrast, nearly all mammalian cells divide 20 to 50 times under culture conditions
before they stop, age, and die.
 Cancer cells may be “immortal.”
 HeLa cells from a tumor removed from a woman (Henrietta Lacks) in 1951 are still
reproducing in culture.
 The abnormal behavior of cancer cells begins when a single cell in a tissue undergoes a
transformation that converts it from a normal cell to a cancer cell.
 Normally, the immune system recognizes and destroys transformed cells.
 However, cells that evade destruction proliferate to form a tumor, a mass of abnormal
 If the abnormal cells remain at the originating site, the lump is called a benign tumor.
 Most do not cause serious problems and can be fully removed by surgery.
 In a malignant tumor, the cells become invasive enough to impair the functions of one or
more organs.
 In addition to chromosomal and metabolic abnormalities, cancer cells often lose
attachment to nearby cells, are carried by the blood and lymph system to other tissues, and
start more tumors in an event called metastasis.
 Cancer cells are abnormal in many ways.
 They may have an unusual number of chromosomes, their metabolism may be
disabled, and they may cease to function in any constructive way.
 Cancer cells may secrete signal molecules that cause blood vessels to grow toward the
 Treatments for metastasizing cancers include high-energy radiation and chemotherapy
with toxic drugs.
 These treatments target actively dividing cells.
 Chemotherapeutic drugs interfere with specific steps in the cell cycle.
 For example, Taxol prevents mitotic depolymerization, preventing cells from
proceeding past metaphase.
 The side effects of chemotherapy are due to the drug’s effects on normal cells.
 Researchers are beginning to understand how a normal cell is transformed into a cancer
 The causes are diverse, but cellular transformation always involves the alteration of
genes that influence the cell cycle control system.

Biology Chapter Notes

Chapter 13 Meiosis and Sexual Life Cycles
Chapter Notes

Overview: Hereditary Similarity and Variation

 Living organisms are distinguished by their ability to reproduce their own kind.
 Offspring resemble their parents more than they do less closely related individuals of the
same species.
 The transmission of traits from one generation to the next is called heredity or inheritance.
 However, offspring differ somewhat from parents and siblings, demonstrating variation.
 Farmers have bred plants and animals for desired traits for thousands of years, but the
mechanisms of heredity and variation eluded biologists until the development of genetics
in the 20th century.
 Genetics is the scientific study of heredity and variation.

Concept 13.1 Offspring acquire genes from parents by inheriting chromosomes

 Parents endow their offspring with coded information in the form of genes.
 Your genome is comprised of the tens of thousands of genes that you inherited from
your mother and your father.
 Genes program specific traits that emerge as we develop from fertilized eggs into adults.
 Genes are segments of DNA. Genetic information is transmitted as specific sequences of
the four deoxyribonucleotides in DNA.
 This is analogous to the symbolic information of language in which words and
sentences are translated into mental images.
 Cells translate genetic “sentences” into freckles and other features with no resemblance
to genes.
 Most genes program cells to synthesize specific enzymes and other proteins whose
cumulative action produces an organism’s inherited traits.
 The transmission of hereditary traits has its molecular basis in the precise replication of
 This produces copies of genes that can be passed from parents to offspring.
 In plants and animals, sperm and ova (unfertilized eggs) transmit genes from one
generation to the next.
 After fertilization (fusion of a sperm cell and an ovum), genes from both parents are
present in the nucleus of the fertilized egg, or zygote.
 Almost all the DNA in a eukaryotic cell is subdivided into chromosomes in the nucleus.
 Tiny amounts of DNA are also found in mitochondria and chloroplasts.
 Every living species has a characteristic number of chromosomes.
 Humans have 46 chromosomes in almost all of their cells.
 Each chromosome consists of a single DNA molecule associated with various proteins.

Biology Chapter Notes

 Each chromosome has hundreds or thousands of genes, each at a specific location, its
Like begets like, more or less: a comparison of asexual and sexual reproduction.
 Only organisms that reproduce asexually can produce offspring that are exact copies of
 In asexual reproduction, a single individual is the sole parent to donate genes to its
 Single-celled eukaryotes can reproduce asexually by mitotic cell division to produce
two genetically identical daughter cells.
 Some multicellular eukaryotes, like Hydra, can reproduce by budding, producing a
mass of cells by mitosis.
 An individual that reproduces asexually gives rise to a clone, a group of genetically
identical individuals.
 Members of a clone may be genetically different as a result of mutation.
 In sexual reproduction, two parents produce offspring that have unique combinations of
genes inherited from the two parents.
 Unlike a clone, offspring produced by sexual reproduction vary genetically from their
siblings and their parents.

Concept 13.2 Fertilization and meiosis alternate in sexual life cycles

 A life cycle is the generation-to-generation sequence of stages in the reproductive history
of an organism.
 It starts at the conception of an organism and continues until the organism produces its
own offspring.
Human cells contain sets of chromosomes.
 In humans, each somatic cell (all cells other than sperm or ovum) has 46 chromosomes.
 Each chromosome can be distinguished by size, position of the centromere, and pattern
of staining with certain dyes.
 Images of the 46 human chromosomes can be arranged in pairs in order of size to produce
a karyotype display.
 The two chromosomes comprising a pair have the same length, centromere position,
and staining pattern.
 These homologous chromosome pairs carry genes that control the same inherited
 Two distinct sex chromosomes, the X and the Y, are an exception to the general pattern
of homologous chromosomes in human somatic cells.
 The other 22 pairs are called autosomes.
 The pattern of inheritance of the sex chromosomes determines an individual’s sex.
 Human females have a homologous pair of X chromosomes (XX).
 Human males have an X and a Y chromosome (XY).
 Only small parts of the X and Y are homologous.
 Most of the genes carried on the X chromosome do not have counterparts on the tiny
Biology Chapter Notes
 The Y chromosome also has genes not present on the X.
 The occurrence of homologous pairs of chromosomes is a consequence of sexual
 We inherit one chromosome of each homologous pair from each parent.
 The 46 chromosomes in each somatic cell are two sets of 23, a maternal set (from your
mother) and a paternal set (from your father).
 The number of chromosomes in a single set is represented by n.
 Any cell with two sets of chromosomes is called a diploid cell and has a diploid number
of chromosomes, abbreviated as 2n.
 Sperm cells or ova (gametes) have only one set of chromosomes—22 autosomes and an
X (in an ovum) and 22 autosomes and an X or a Y (in a sperm cell).
 A gamete with a single chromosome set is haploid, abbreviated as n.
 Any sexually reproducing species has a characteristic haploid and diploid number of
 For humans, the haploid number of chromosomes is 23 (n = 23), and the diploid
number is 46 (2n = 46).
Let’s discuss the role of meiosis in the human life cycle.
 The human life cycle begins when a haploid sperm cell fuses with a haploid ovum.
 These cells fuse (syngamy), resulting in fertilization.
 The fertilized egg (zygote) is diploid because it contains two haploid sets of chromosomes
bearing genes from the maternal and paternal family lines.
 As an organism develops from a zygote to a sexually mature adult, mitosis generates all
the somatic cells of the body.
 Each somatic cell contains a full diploid set of chromosomes.
 Gametes, which develop in the gonads (testes or ovaries), are not produced by mitosis.
 If gametes were produced by mitosis, the fusion of gametes would produce offspring
with four sets of chromosomes after one generation, eight after a second, and so on.
 Instead, gametes undergo the process of meiosis in which the chromosome number is
 Human sperm or ova have a haploid set of 23 different chromosomes, one from each
homologous pair.
 Fertilization restores the diploid condition by combining two haploid sets of
Organisms display a variety of sexual life cycles.
 Fertilization and meiosis alternate in all sexual life cycles.
 However, the timing of meiosis and fertilization does vary among species.
 These variations can be grouped into three main types of life cycles.
 In most animals, including humans, gametes are the only haploid cells.
 Gametes do not divide but fuse to form a diploid zygote that divides by mitosis to
produce a multicellular organism.
 Plants and some algae have a second type of life cycle called alternation of generations.
 This life cycle includes two multicellular stages, one haploid and one diploid.
Biology Chapter Notes
 The multicellular diploid stage is called the sporophyte.
 Meiosis in the sporophyte produces haploid spores that develop by mitosis into the
haploid gametophyte stage.
 Gametes produced via mitosis by the gametophyte fuse to form the zygote, which
grows into the sporophyte by mitosis.
 Most fungi and some protists have a third type of life cycle.
 Gametes fuse to form a zygote, which is the only diploid phase.
 The zygote undergoes meiosis to produce haploid cells.
 These haploid cells grow by mitosis to form the haploid multicellular adult organism.
 The haploid adult produces gametes by mitosis.
 Note that either haploid or diploid cells can divide by mitosis, depending on the type of
life cycle. However, only diploid cells can undergo meiosis.
 Although the three types of sexual life cycles differ in the timing of meiosis and
fertilization, they share a fundamental feature: each cycle of chromosome halving and
doubling contributes to genetic variation among offspring.

Concept 13.3 Meiosis reduces the number of chromosome sets from diploid to haploid
 Many steps of meiosis resemble steps in mitosis.
 Both are preceded by the replication of chromosomes.
 However, in meiosis, there are two consecutive cell divisions, meiosis I and meiosis II,
resulting in four daughter cells.
 The first division, meiosis I, separates homologous chromosomes.
 The second, meiosis II, separates sister chromatids.
 The four daughter cells have only half as many chromosomes as the parent cell.
 Meiosis I is preceded by interphase, in which the chromosomes are replicated to form
sister chromatids.
 These are genetically identical and joined at the centromere.
 The single centrosome is replicated, forming two centrosomes.
 Division in meiosis I occurs in four phases: prophase I, metaphase I, anaphase I, and
telophase I.
Prophase I
 Prophase I typically occupies more than 90% of the time required for meiosis.
 During prophase I, the chromosomes begin to condense.
 Homologous chromosomes loosely pair up along their length, precisely aligned gene for
 In crossing over, DNA molecules in nonsister chromatids break at corresponding
places and then rejoin the other chromatid.
 In synapsis, a protein structure called the synaptonemal complex forms between
homologues, holding them tightly together along their length.
 As the synaptonemal complex disassembles in late prophase, each chromosome pair
becomes visible as a tetrad, or group of four chromatids.
 Each tetrad has one or more chiasmata, sites where the chromatids of homologous
chromosomes have crossed and segments of the chromatids have been traded.
Biology Chapter Notes
 Spindle microtubules form from the centrosomes, which have moved to the poles.
 The breakdown of the nuclear envelope and nucleoli take place.
 Kinetochores of each homologue attach to microtubules from one of the poles.
Metaphase I
 At metaphase I, the tetrads are all arranged at the metaphase plate, with one chromosome
facing each pole.
 Microtubules from one pole are attached to the kinetochore of one chromosome of
each tetrad, while those from the other pole are attached to the other.
Anaphase I
 In anaphase I, the homologous chromosomes separate. One chromosome moves toward
each pole, guided by the spindle apparatus.
 Sister chromatids remain attached at the centromere and move as a single unit toward the
Telophase I and cytokinesis
 In telophase I, movement of homologous chromosomes continues until there is a haploid
set at each pole.
 Each chromosome consists of two sister chromatids.
 Cytokinesis usually occurs simultaneously, by the same mechanisms as mitosis.
 In animal cells, a cleavage furrow forms. In plant cells, a cell plate forms.
 No chromosome replication occurs between the end of meiosis I and the beginning of
meiosis II, as the chromosomes are already replicated.
Meiosis II
 Meiosis II is very similar to mitosis.
 During prophase II, a spindle apparatus forms and attaches to kinetochores of each
sister chromatid.
 Spindle fibers from one pole attach to the kinetochore of one sister chromatid, and
those of the other pole attach to kinetochore of the other sister chromatid.
 At metaphase II, the sister chromatids are arranged at the metaphase plate.
 Because of crossing over in meiosis I, the two sister chromatids of each chromosome
are no longer genetically identical.
 The kinetochores of sister chromatids attach to microtubules extending from opposite
 At anaphase II, the centomeres of sister chromatids separate and two newly individual
chromosomes travel toward opposite poles.
 In telophase II, the chromosomes arrive at opposite poles.
 Nuclei form around the chromosomes, which begin expanding, and cytokinesis
separates the cytoplasm.
 At the end of meiosis, there are four haploid daughter cells.
There are key differences between mitosis and meiosis.
 Mitosis and meiosis have several key differences.

Biology Chapter Notes

 The chromosome number is reduced from diploid to haploid in meiosis but is
conserved in mitosis.
 Mitosis produces daughter cells that are genetically identical to the parent and to each
 Meiosis produces cells that are genetically distinct from the parent cell and from each
 Three events, unique to meiosis, occur during the first division cycle.
o During prophase I of meiosis, replicated homologous chromosomes line up and
become physically connected along their lengths by a zipperlike protein complex, the
synaptonemal complex, in a process called synapsis. Genetic rearrangement between
nonsister chromatids called crossing over also occurs. Once the synaptonemal complex
is disassembled, the joined homologous chromosomes are visible as a tetrad. X-shaped
regions called chiasmata are visible as the physical manifestation of crossing over.
Synapsis and crossing over do not occur in mitosis.
o At metaphase I of meiosis, homologous pairs of chromosomes align along the
metaphase plate. In mitosis, individual replicated chromosomes line up along the
metaphase plate.
o At anaphase I of meiosis, it is homologous chromosomes, not sister chromatids, that
separate and are carried to opposite poles of the cell. Sister chromatids of each
replicated chromosome remain attached. In mitosis, sister chromatids separate to
become individual chromosomes.
 Meiosis I is called the reductional division because it halves the number of chromosome
sets per cell—a reduction from the diploid to the haploid state.
 The sister chromatids separate during the second meiosis division, meiosis II.

Concept 13.4 Genetic variation produced in sexual life cycles contributes to evolution
 What is the origin of genetic variation?
 Mutations are the original source of genetic diversity.
 Once different versions of genes arise through mutation, reshuffling during meiosis and
fertilization produce offspring with their own unique set of traits.
Sexual life cycles produce genetic variation among offspring.
 The behavior of chromosomes during meiosis and fertilization is responsible for most of
the variation that arises in each generation.
 Three mechanisms contribute to genetic variation:
o Independent assortment of chromosomes.
o Crossing over.
o Random fertilization.
 Independent assortment of chromosomes contributes to genetic variability due to the
random orientation of homologous pairs of chromosomes at the metaphase plate during
meiosis I.
 There is a fifty-fifty chance that a particular daughter cell of meiosis I will get the
maternal chromosome of a certain homologous pair and a fifty-fifty chance that it will
receive the paternal chromosome.
 Each homologous pair of chromosomes segregates independently of the other
homologous pairs during metaphase I.
Biology Chapter Notes
 Therefore, the first meiotic division results in independent assortment of maternal and
paternal chromosomes into daughter cells.
 The numbern of combinations possible when chromosomes assort independently into
gametes is 2 , where n is the haploid number of the organism.
 If n = 3, there are 23 = 8 possible combinations.
 For humans with n = 23, there are 223, or more than 8 million possible combinations of
 Crossing over produces recombinant chromosomes, which combine genes inherited
from each parent.
 Crossing over begins very early in prophase I as homologous chromosomes pair up gene
by gene.
 In crossing over, homologous portions of two nonsister chromatids trade places.
 For humans, this occurs an average of one to three times per chromosome pair.
 Recent research suggests that, in some organisms, crossing over may be essential for
synapsis and the proper assortment of chromosomes in meiosis I.
 Crossing over, by combining DNA inherited from two parents into a single chromosome,
is an important source of genetic variation.
 At metaphase II, nonidentical sister chromatids sort independently from one another,
increasing by even more the number of genetic types of daughter cells that are formed by
 The random nature of fertilization adds to the genetic variation arising from meiosis.
 Any sperm can fuse with any egg.
 The ovum is one of more than 8 million possible chromosome combinations.
 The successful sperm is one of more than 8 million possibilities.
 The resulting zygote could contain any one of more than 70 trillion possible
combinations of chromosomes.
 Crossing over adds even more variation to this.
 Each zygote has a unique genetic identity.
 The three sources of genetic variability in a sexually reproducing organism are:
o Independent assortment of homologous chromosomes during meiosis I and of
nonidentical sister chromatids during meiosis II.
o Crossing over between homologous chromosomes during prophase I.
o Random fertilization of an ovum by a sperm.
 All three mechanisms reshuffle the various genes carried by individual members of a
Evolutionary adaptation depends on a population’s genetic variation.
 Darwin recognized the importance of genetic variation in evolution.
 A population evolves through the differential reproductive success of its variant
 Those individuals best suited to the local environment leave the most offspring,
transmitting their genes in the process.
 This natural selection results in adaptation, the accumulation of favorable genetic

Biology Chapter Notes

 If the environment changes or a population moves to a new environment, new genetic
combinations that work best in the new conditions will produce more offspring, and these
genes will increase.
 The formerly favored genes will decrease.
 Sex and mutation continually generate new genetic variability.
 Although Darwin realized that heritable variation makes evolution possible, he did not
have a theory of inheritance.
 Gregor Mendel, a contemporary of Darwin’s, published a theory of inheritance that
supported Darwin’s theory.
 However, this work was largely unknown until 1900, after Darwin and Mendel had
both been dead for more than 15 years.

Biology Chapter Notes

Chapter 14 Mendel and the Gene Idea
Chapter Notes

Overview: Drawing from the Deck of Genes

 Every day we observe heritable variations (such as brown, green, or blue eyes) among
individuals in a population.
 These traits are transmitted from parents to offspring.
 One possible explanation for heredity is a “blending” hypothesis.
 This hypothesis proposes that genetic material contributed by each parent mixes in a
manner analogous to the way blue and yellow paints blend to make green.
 With blending inheritance, a freely mating population will eventually give rise to a
uniform population of individuals.
 Everyday observations and the results of breeding experiments tell us that heritable
traits do not blend to become uniform.
 An alternative model, “particulate” inheritance, proposes that parents pass on discrete
heritable units, genes, that retain their separate identities in offspring.
 Genes can be sorted and passed on, generation after generation, in undiluted form.
 Modern genetics began in an abbey garden, where a monk named Gregor Mendel
documented a particulate mechanism of inheritance.

Concept 14.1 Mendel used the scientific approach to identify two laws of inheritance
 Mendel discovered the basic principles of heredity by breeding garden peas in carefully
planned experiments.
 Mendel grew up on a small farm in what is today the Czech Republic.
 In 1843, Mendel entered an Augustinian monastery.
 He studied at the University of Vienna from 1851 to 1853, where he was influenced by a
physicist who encouraged experimentation and the application of mathematics to science
and by a botanist who stimulated Mendel’s interest in the causes of variation in plants.
 These influences came together in Mendel’s experiments.
 After university, Mendel taught at the Brunn Modern School and lived in the local
 The monks at this monastery had a long tradition of interest in the breeding of plants,
including peas.
 Around 1857, Mendel began breeding garden peas to study inheritance.
 Pea plants have several advantages for genetic study.
 Pea plants are available in many varieties with distinct heritable features, or
characters, with different variant traits.
 Mendel could strictly control which plants mated with which.
 Each pea plant has male (stamens) and female (carpal) sexual organs.
 In nature, pea plants typically self-fertilize, fertilizing ova with the sperm nuclei from
their own pollen.
Biology Chapter Notes
 However, Mendel could also use pollen from another plant for cross-pollination.
 Mendel tracked only those characters that varied in an “either-or” manner, rather than a
“more-or-less” manner.
 For example, he worked with flowers that were either purple or white.
 He avoided traits, such as seed weight, that varied on a continuum.
 Mendel started his experiments with varieties that were true-breeding.
 When true-breeding plants self-pollinate, all their offspring have the same traits.
 In a typical breeding experiment, Mendel would cross-pollinate (hybridize) two
contrasting, true-breeding pea varieties.
 The true-breeding parents are the P generation, and their hybrid offspring are the F1
 Mendel would then allow the F1 hybrids to self-pollinate to produce an F2 generation.
 It was mainly Mendel’s quantitative analysis of F 2 plants that revealed two fundamental
principles of heredity: the law of segregation and the law of independent assortment.
By the law of segregation, the two alleles for a character are separated during the
formation of gametes.
 If the blending model was correct, the F1 hybrids from a cross between purple-flowered
and white-flowered pea plants would have pale purple flowers.
 Instead, F1 hybrids all have purple flowers, just as purple as their purple-flowered parents.
 When Mendel allowed the F1 plants to self-fertilize, the F2 generation included both
purple-flowered and white-flowered plants.
 The white trait, absent in the F1, reappeared in the F2.
 Mendel used very large sample sizes and kept accurate records of his results.
 Mendel recorded 705 purple-flowered F2 plants and 224 white-flowered F2 plants.
 This cross produced a traits ratio of three purple to one white in the F2 offspring.
 Mendel reasoned that the heritable factor for white flowers was present in the F 1 plants,
but did not affect flower color.
 Purple flower color is a dominant trait, and white flower color is a recessive trait.
 The reappearance of white-flowered plants in the F2 generation indicated that the heritable
factor for the white trait was not diluted or “blended” by coexisting with the purple-flower
factor in F1 hybrids.
 Mendel found similar 3-to-1 ratios of two traits among F2 offspring when he conducted
crosses for six other characters, each represented by two different traits.
 For example, when Mendel crossed two true-breeding varieties, one producing round
seeds and the other producing wrinkled seeds, all the F1 offspring had round seeds.
 In the F2 plants, 75% of the seeds were round and 25% were wrinkled.
 Mendel developed a hypothesis to explain these results that consisted of four related
ideas. We will explain each idea with the modern understanding of genes and
o Alternative versions of genes account for variations in inherited characters.
 The gene for flower color in pea plants exists in two versions, one for purple flowers
and one for white flowers.
 These alternate versions are called alleles.
 Each gene resides at a specific locus on a specific chromosome.
Biology Chapter Notes
 The DNA at that locus can vary in its sequence of nucleotides.
 The purple-flower and white-flower alleles are two DNA variations at the flower-color
o For each character, an organism inherits two alleles, one from each parent.
 A diploid organism inherits one set of chromosomes from each parent.
 Each diploid organism has a pair of homologous chromosomes and, therefore, two
copies of each gene.
 These homologous loci may be identical, as in the true-breeding plants of the P
 Alternatively, the two alleles may differ.
o If the two alleles at a locus differ, then one, the dominant allele, determines the
organism’s appearance. The other, the recessive allele, has no noticeable effect on the
organism’s appearance.
 In the flower-color example, the F1 plants inherited a purple-flower allele from one
parent and a white-flower allele from the other.
 They had purple flowers because the allele for that trait is dominant.
o 4. Mendel’s law of segregation states that the two alleles for a heritable character
separate and segregate during gamete production and end up in different gametes.
 This segregation of alleles corresponds to the distribution of homologous
chromosomes to different gametes in meiosis.
 If an organism has two identical alleles for a particular character, then that allele is
present as a single copy in all gametes.
 If different alleles are present, then 50% of the gametes will receive one allele and
50% will receive the other.
 Mendel’s law of segregation accounts for the 3:1 ratio that he observed in the F 2
 The F1 hybrids produce two classes of gametes, half with the purple-flower allele and half
with the white-flower allele.
 During self-pollination, the gametes of these two classes unite randomly.
 This produces four equally likely combinations of sperm and ovum.
 A Punnett square predicts the results of a genetic cross between individuals of known
 Let us describe a Punnett square analysis of the flower-color example.
 We will use a capital letter to symbolize the dominant allele and a lowercase letter to
symbolize the recessive allele.
 P is the purple-flower allele, and p is the white-flower allele.
 What will be the physical appearance of the F2 offspring?
 One in four F2 offspring will inherit two white-flower alleles and produce white
 Half of the F2 offspring will inherit one white-flower allele and one purple-flower
allele and produce purple flowers.
 One in four F2 offspring will inherit two purple-flower alleles and produce purple
 Mendel’s model accounts for the 3:1 ratio in the F2 generation.
 An organism with two identical alleles for a character is homozygous for that character.
Biology Chapter Notes
 Organisms with two different alleles for a character is heterozygous for that character.
 An organism’s traits are called its phenotype.
 Its genetic makeup is called its genotype.
 Two organisms can have the same phenotype but have different genotypes if one is
homozygous dominant and the other is heterozygous.
 For flower color in peas, the only individuals with white flowers are those that are
homozygous recessive (pp) for the flower-color gene.
 However, PP and Pp plants have the same phenotype (purple flowers) but different
genotypes (homozygous dominant and heterozygous).
 How can we tell the genotype of an individual with the dominant phenotype?
 The organism must have one dominant allele, but could be homozygous dominant or
 The answer is to carry out a testcross.
 The mystery individual is bred with a homozygous recessive individual.
 If any of the offspring display the recessive phenotype, the mystery parent must be
By the law of independent assortment, each pair of alleles segregates independently into
 Mendel’s first experiments followed only a single character, such as flower color.
 All F1 progeny produced in these crosses were monohybrids, heterozygous for one
 A cross between two heterozygotes is a monohybrid cross.
 Mendel identified the second law of inheritance by following two characters at the same
 In one such dihybrid cross, Mendel studied the inheritance of seed color and seed shape.
 The allele for yellow seeds (Y) is dominant to the allele for green seeds (y).
 The allele for round seeds (R) is dominant to the allele for wrinkled seeds (r).
 Mendel crossed true-breeding plants that had yellow, round seeds (YYRR) with true-
breeding plants that has green, wrinkled seeds (yyrr).
 One possibility is that the two characters are transmitted from parents to offspring as a
 The Y and R alleles and y and r alleles stay together.
 If this were the case, the F1 offspring would produce yellow, round seeds.
 The F2 offspring would produce two phenotypes (yellow + round; green + wrinkled) in a
3:1 ratio, just like a monohybrid cross.
 This was not consistent with Mendel’s results.
 An alternative hypothesis is that the two pairs of alleles segregate independently of each
 The presence of a specific allele for one trait in a gamete has no impact on the presence
of a specific allele for the second trait.
 In our example, the F1 offspring would still produce yellow, round seeds.
 However, when the F1s produced gametes, genes would be packaged into gametes with all
possible allelic combinations.
Biology Chapter Notes
 Four classes of gametes (YR, Yr, yR, and yr) would be produced in equal amounts.
 When sperm with four classes of alleles and ova with four classes of alleles combined,
there would be 16 equally probable ways in which the alleles can combine in the F 2
 These combinations produce four distinct phenotypes in a 9:3:3:1 ratio.
 This was consistent with Mendel’s results.
 Mendel repeated the dihybrid cross experiment for other pairs of characters and always
observed a 9:3:3:1 phenotypic ratio in the F2 generation.
 Each character appeared to be inherited independently.
 If you follow just one character in these crosses, you will observe a 3:1 F 2 ratio, just as if
this were a monohybrid cross.
 The independent assortment of each pair of alleles during gamete formation is now called
Mendel’s law of independent assortment.
 Mendel’s law of independent assortment states that each pair of alleles segregates
independently during gamete formation.
 Strictly speaking, this law applies only to genes located on different, nonhomologous
 Genes located near each other on the same chromosome tend to be inherited together and
have more complex inheritance patterns than those predicted for the law of independent

Concept 14.2 The laws of probability govern Mendelian inheritance

 Mendel’s laws of segregation and independent assortment reflect the same laws of
probability that apply to tossing coins or rolling dice.
 The probability scale ranges from 0 (an event with no chance of occurring) to 1 (an event
that is certain to occur).
 The probability of tossing heads with a normal coin is 1/2.
 The probability of rolling a 3 with a six-sided die is 1/6, and the probability of rolling
any other number is 1 − 1/6 = 5/6.
 When tossing a coin, the outcome of one toss has no impact on the outcome of the next
 Each toss is an independent event, just like the distribution of alleles into gametes.
 Like a coin toss, each ovum from a heterozygous parent has a 1/2 chance of carrying
the dominant allele and a 1/2 chance of carrying the recessive allele.
 The same odds apply to the sperm.
 We can use the multiplication rule to determine the chance that two or more independent
events will occur together in some specific combination.
 Compute the probability of each independent event.
 Multiply the individual probabilities to obtain the overall probability of these events
occurring together.
 The probability that two coins tossed at the same time will land heads up is 1/2 × 1/2 =

Biology Chapter Notes

 Similarly, the probability that a heterozygous pea plant (Pp) will self-fertilize to
produce a white-flowered offspring (pp) is the chance that a sperm with a white allele
will fertilize an ovum with a white allele.
 This probability is 1/2 × 1/2 = 1/4.
 The rule of multiplication also applies to dihybrid crosses.
 For a heterozygous parent (YyRr) the probability of producing a YR gamete is 1/2 × 1/2
= 1/4.
 We can use this to predict the probability of a particular F 2 genotype without
constructing a 16-part Punnett square.
 The probability that an F2 plant from heterozygous parents will have a YYRR genotype
is 1/16 (1/4 chance for a YR ovum and 1/4 chance for a YR sperm).
 The rule of addition also applies to genetic problems.
 Under the rule of addition, the probability of an event that can occur two or more different
ways is the sum of the separate probabilities of those ways.
 For example, there are two ways that F1 gametes can combine to form a heterozygote.
 The dominant allele could come from the sperm and the recessive from the ovum
(probability = 1/4).
 Or the dominant allele could come from the ovum and the recessive from the sperm
(probability = 1/4).
 The probability of obtaining a heterozygote is 1/4 + 1/4 = 1/2.
 We can combine the rules of multiplication and addition to solve complex problems in
Mendelian genetics.
 Let’s determine the probability of an offspring having two recessive phenotypes for at
least two of three traits resulting from a trihybrid cross between pea plants that are
PpYyRr and Ppyyrr.
 There are five possible genotypes that fulfill this condition: ppyyRr, ppYyrr, Ppyyrr,
PPyyrr, and ppyyrr.
 We can use the rule of multiplication to calculate the probability for each of these
genotypes and then use the rule of addition to pool the probabilities for fulfilling the
condition of at least two recessive traits.
 The probability of producing a ppyyRr offspring:
 The probability of producing pp = 1/2 × 1/2 = 1/4.
 The probability of producing yy = 1/2 × 1 = 1/2.
 The probability of producing Rr = 1/2 × 1 = 1/2.
 Therefore, the probability of all three being present (ppyyRr) in one offspring is 1/4 ×
1/2 × 1/2 = 1/16.
 For ppYyrr: 1/4 × 1/2 × 1/2 = 1/16.
 For Ppyyrr: 1/2 × 1/2 × 1/2 = 1/8 or 2/16.
 For PPyyrr: 1/4 × 1/2 × 1/2 = 1/16.
 For ppyyrr: 1/4 × 1/2 × 1/2 = 1/16.
 Therefore, the chance that a given offspring will have at least two recessive traits is 1/16 +
2/16 + 1/16 + 1/16 = 6/16.
Mendel discovered the particulate behavior of genes: a review.

Biology Chapter Notes

 While we cannot predict with certainty the genotype or phenotype of any particular seed
from the F2 generation of a dihybrid cross, we can predict the probability that it will have
a specific genotype or phenotype.
 Mendel’s experiments succeeded because he counted so many offspring, was able to
discern the statistical nature of inheritance, and had a keen sense of the rules of chance.
 Mendel’s laws of independent assortment and segregation explain heritable variation in
terms of alternative forms of genes that are passed along according to simple rules of
 These laws apply not just to garden peas, but to all diploid organisms that reproduce by
sexual reproduction.
 Mendel’s studies of pea inheritance endure not only in genetics, but as a case study of the
power of scientific reasoning using the hypothetico-deductive approach.

Concept 14.3 Inheritance patterns are often more complex than predicted by simple
Mendelian genetics
 In the 20th century, geneticists have extended Mendelian principles not only to diverse
organisms, but also to patterns of inheritance more complex than Mendel described.
 In fact, Mendel had the good fortune to choose a system that was relatively simple
 Each character that Mendel studied is controlled by a single gene.
 Each gene has only two alleles, one of which is completely dominant to the other.
 The heterozygous F1 offspring of Mendel’s crosses always looked like one of the parental
varieties because one allele was dominant to the other.
 The relationship between genotype and phenotype is rarely so simple.
 The inheritance of characters determined by a single gene deviates from simple
Mendelian patterns when alleles are not completely dominant or recessive, when a gene
has more than two alleles, or when a gene produces multiple phenotypes.
 We will consider examples of each of these situations.
 Alleles show different degrees of dominance and recessiveness in relation to each other.
 One extreme is the complete dominance characteristic of Mendel’s crosses.
 At the other extreme from complete dominance is codominance, in which two alleles
affect the phenotype in separate, distinguishable ways.
 For example, the M, N, and MN blood groups of humans are due to the presence of
two specific molecules on the surface of red blood cells.
 People of group M (genotype MM) have one type of molecule on their red blood cells,
people of group N (genotype NN) have the other type, and people of group MN
(genotype MN) have both molecules present.
 The MN phenotype is not intermediate between M and N phenotypes but rather
exhibits both the M and the N phenotype.
 Some alleles show incomplete dominance, in which heterozygotes show a distinct
intermediate phenotype not seen in homozygotes.
 This is not blending inheritance because the traits are separable (particulate), as shown
in further crosses.

Biology Chapter Notes

 Offspring of a cross between heterozygotes show three phenotypes: each parental and
the heterozygote.
 The phenotypic and genotypic ratios are identical: 1:2:1.
 A clear example of incomplete dominance is seen in flower color of snapdragons.
 A cross between a white-flowered plant and a red-flowered plant will produce all pink
F1 offspring.
 Self-pollination of the F1 offspring produces 25% white, 25% red, and 50% pink F2
 The relative effects of two alleles range from complete dominance of one allele, through
incomplete dominance of either allele, to codominance of both alleles.
 It is important to recognize that a dominant allele does not somehow subdue a recessive
 Alleles are simply variations in a gene’s nucleotide sequence.
 When a dominant allele coexists with a recessive allele in a heterozygote, they do not
interact at all.
 To illustrate the relationship between dominance and phenotype, let us consider Mendel’s
character of round versus wrinkled pea seed shape.
 Pea plants with wrinkled seeds have two copies of the recessive allele.
 The seeds are wrinkled due to the accumulation of monosaccharides because of the
lack of a key enzyme that converts them to starch.
 Excess water enters the seed due to the accumulation of monosaccharides.
 The seeds wrinkle when the excess water dries.
 Both homozygous dominants and heterozygotes produce enough enzymes to convert
all the monosaccharides into starch.
 As a result, they do not fill with excess water and form smooth seeds as they dry.
 For any character, dominance/recessiveness relationships depend on the level at which we
examine the phenotype.
 For example, humans with Tay-Sachs disease lack a functioning enzyme to
metabolize certain lipids. These lipids accumulate in the brain, harming brain cells, and
ultimately leading to death.
 Children with two Tay-Sachs alleles (homozygotes) have the disease.
 Both heterozygotes with one working allele and homozygotes with two working alleles
are healthy and normal at the organismal level.
 The activity level of the lipid-metabolizing enzyme is reduced in heterozygotes. At the
biochemical level, the alleles show incomplete dominance.
 Heterozygous individuals produce equal numbers of normal and dysfunctional enzyme
molecules. At the molecular level, the Tay-Sachs and functional alleles are
 A dominant allele is not necessarily more common in a population than the recessive
 For example, one baby in 400 is born with polydactyly, a condition in which
individuals are born with extra fingers or toes.
 Polydactyly is due to a dominant allele.
 However, the recessive allele is far more prevalent than the dominant allele.
 399 individuals out of 400 have five digits per appendage.
 Many genes exist in populations in more than two allelic forms.
Biology Chapter Notes
 The ABO blood groups in humans are determined by three alleles, IA, IB, and i.
 Both the IA and IB alleles are dominant to the i allele.
 The IA and IB alleles are codominant to each other.
 Because each individual carries two alleles, there are six possible genotypes and four
possible blood types.
 Individuals that are IAIA or IAi are type A and have type A carbohydrates on the surface
of their red blood cells.
 Individuals that are IBIB or IBi are type B and have type B carbohydrates on the surface
of their red blood cells.
 Individuals that are IAIB are type AB and have both type A and type B carbohydrates
on the surface of their red blood cells.
 Individuals that are ii are type O and have neither carbohydrate on the surface of their
red blood cells.
 Matching compatible blood groups is critical for blood transfusions because a person
produces antibodies against foreign blood factors.
 If the donor’s blood has an A or B carbohydrate that is foreign to the recipient,
antibodies in the recipient’s blood will bind to the foreign molecules, cause the
donated blood cells to clump together, and can kill the recipient.
 The genes that we have covered so far affect only one phenotypic character.
 However, most genes are pleiotropic, affecting more than one phenotypic character.
 For example, the wide-ranging symptoms of sickle-cell disease are due to a single
 Considering the intricate molecular and cellular interactions responsible for an organism’s
development, it is not surprising that a gene can affect a number of characteristics.
 In epistasis, a gene at one locus alters the phenotypic expression of a gene at a second
 For example, in mice and many other mammals, coat color depends on two genes.
 One, the epistatic gene, determines whether pigment will be deposited in hair or not.
 Presence (C) is dominant to absence (c) of pigment.
 The second gene determines whether the pigment to be deposited is black (B) or brown
 The black allele is dominant to the brown allele.
 An individual that is cc has a white (albino) coat regardless of the genotype of the
second gene.
 A cross between two black mice that are heterozygous (BbCc) will follow the law of
independent assortment.
 However, unlike the 9:3:3:1 offspring ratio of a normal Mendelian experiment, the
offspring ratio is nine black, three brown, and four white.
 All cc mice will be albino, regardless of the alleles they inherit at the B gene.
 Some characters cannot be classified as either-or, as Mendel’s genes were.
 Quantitative characters vary in a population along a continuum.
 These are usually due to polygenic inheritance, the additive effects of two or more genes
on a single phenotypic character.
 For example, skin color in humans is controlled by at least three independent genes.

Biology Chapter Notes

 Imagine that each gene has two alleles, one light and one dark, which demonstrate
incomplete dominance.
 An AABBCC individual is very dark; an aabbcc individual is very light.
 A cross between two AaBbCc individuals (with intermediate skin shade) will produce
offspring covering a wide range of shades.
 Individuals with intermediate skin shades will be most common, but some very light
and very dark individuals could be produced as well.
 The range of phenotypes will form a normal distribution, if the number of offspring is
great enough.
 Phenotype depends on environment and genes.
 A person becomes darker if they tan, despite their inherited skin color.
 A single tree may have leaves that vary in size, shape, and greenness, depending on
exposure to wind and sun.
 For humans, nutrition influences height, exercise alters build, sun-tanning darkens
skin, and experience improves performance on intelligence tests.
 Even identical twins, who are genetically identical, accumulate phenotypic differences
as a result of their unique experiences.
 The relative importance of genes and the environment in influencing human
characteristics is a very old and hotly contested debate.
 The product of a genotype is generally not a rigidly defined phenotype, but a range of
phenotypic possibilities, the norm of reaction, that are determined by the environment.
 In some cases, the norm of reaction has no breadth, and a given genotype specifies a
particular phenotype (for example, blood type).
 In contrast, a person’s red and white blood cell count varies with factors such as
altitude, customary exercise level, and presence of infection.
 Norms of reaction are broadest for polygenic characters.
 For these multifactorial characters, environment contributes to their quantitative
 A reductionist emphasis on single genes and single phenotypic characters presents an
inadequate perspective on heredity and variation.
 A more comprehensive theory of Mendelian genetics must view organisms as a whole.
 The term phenotype can refer not only to specific characters such as flower color or blood
group, but also to an organism in its entirety, including all aspects of its physical
 Genotype can refer not just to a single genetic locus, but also to an organism’s entire
genetic makeup.
 An organism’s phenotype reflects its overall genotype and its unique environmental

Concept 14.4 Many human traits follow Mendelian patterns of inheritance

 While peas are convenient subjects for genetic research, humans are not.
 The generation time is too long, fecundity is too low, and breeding experiments are
 Yet humans are subject to the same rules governing inheritance as other organisms.
Biology Chapter Notes
 New techniques in molecular biology have led to many breakthrough discoveries in the
study of human genetics.
Pedigree analysis reveals Mendelian patterns in human inheritance.
 Rather than manipulate mating patterns of people, geneticists analyze the results of
matings that have already occurred.
 In a pedigree analysis, information about the presence or absence of a particular
phenotypic trait is collected from as many individuals in a family as possible, across
 The distribution of these characters is then mapped on the family tree.
 For example, the occurrence of widow’s peak (W) is dominant to a straight hairline
 Phenotypes of family members and knowledge of dominant/recessive relations
between alleles allow researchers to predict the genotypes of members of this family.
 For example, if an individual in the third generation lacks a widow’s peak, but both her
parents have widow’s peaks, then her parents must be heterozygous for that gene.
 If some siblings in the second generation lack a widow’s peak and one of the
grandparents (first generation) also lacks one, then we know the other grandparent
must be heterozygous, and we can determine the genotype of many other individuals.
 We can use the same family tree to trace the distribution of attached earlobes (f), a
recessive characteristic.
 Individuals with a dominant allele (F) have free earlobes.
 Some individuals may be ambiguous, especially if they have the dominant phenotype and
could be heterozygous or homozygous dominant.
 A pedigree can help us understand the past and predict the future.
 We can use normal Mendelian rules, including multiplication and addition, to predict the
probability of specific phenotypes.
 For example, these rules could be used to predict the probability that a child with
WwFf parents will have a widow’s peak and attached earlobes.
 The chance of having a widow’s peak is 3/4 (1/2 [WW] + 1/4 [Ww]).
 The chance of having attached earlobes is 1/4 [ff].
 This combination has a probability of 3/4 × 1/4 = 3/16.
Many human disorders follow Mendelian patterns of inheritance.
 Thousands of genetic disorders, including disabling or deadly hereditary diseases, are
inherited as simple recessive traits.
 These conditions range from relatively mild (albinism) to life-threatening (cystic
 The recessive behavior of the alleles causing these conditions occurs because the allele
codes for a malfunctioning protein or for no protein at all.
 Heterozygotes have a normal phenotype because one normal allele produces enough of
the required protein.
 A recessively inherited disorder shows up only in homozygous individuals who inherit a
recessive allele from each parent.
 Individuals who lack the disorder are either homozygous dominant or heterozygotes.

Biology Chapter Notes

 While heterozygotes may lack obvious phenotypic effects, they are carriers who may
transmit a recessive allele to their offspring.
 Most people with recessive disorders are born to carriers with normal phenotypes.
 Two carriers have a 1/4 chance of having a child with the disorder, 1/2 chance of
having a child who is a carrier, and 1/4 chance of having a child without a defective
 Genetic disorders are not evenly distributed among all groups of humans.
 This results from the different genetic histories of the world’s people during times when
populations were more geographically and genetically isolated.
 Cystic fibrosis strikes one of every 2,500 whites of European descent.
 One in 25 people of European descent is a carrier for this condition.
 The normal allele for this gene codes for a membrane protein that transports Cl −
between cells and extracellular fluid.
 If these channels are defective or absent, there are abnormally high extracellular levels
of chloride.
 This causes the mucus coats of certain cells to become thicker and stickier than
 This mucus buildup in the pancreas, lungs, digestive tract, and elsewhere causes poor
absorption of nutrients, chronic bronchitis, and bacterial infections.
 Without treatment, affected children die before five, but with treatment, they can live
past their late 20s or even 30s.
 Tay-Sachs disease is another lethal recessive disorder.
 It is caused by a dysfunctional enzyme that fails to break down specific brain lipids.
 The symptoms begin with seizures, blindness, and degeneration of motor and mental
performance a few months after birth.
 Inevitably, the child dies after a few years.
 Among Ashkenazic Jews (those from central Europe), this disease occurs in one of
3,600 births, about 100 times greater than the incidence among non-Jews or
Mediterranean (Sephardic) Jews.
 The most common inherited disease among people of African descent is sickle-cell
disease, which affects one of 400 African-Americans.
 Sickle-cell disease is caused by the substitution of a single amino acid in hemoglobin.
 When oxygen levels in the blood of an affected individual are low, sickle-cell
hemoglobin aggregate into long rods that deform red blood cells into a sickle shape.
 This sickling creates a cascade of symptoms, demonstrating the pleiotropic effects of
this allele, as sickled cells clump and clog capillaries throughout the body.
 Doctors can use regular blood transfusions to prevent brain damage and new drugs to
prevent or treat other problems.
 At the organismal level, the nonsickle allele is incompletely dominant to the sickle-cell
 Carriers are said to have sickle-cell trait.
 These individuals are usually healthy, although some suffer some symptoms of sickle-
cell disease under blood oxygen stress.
 At the molecular level, the two alleles are codominant as both normal and abnormal
(sickle-cell) hemoglobins are synthesized.
 About one in ten African-Americans has sickle-cell trait.
Biology Chapter Notes
 The high frequency of heterozygotes is unusual for an allele with severe detrimental
effects in homozygotes.
 Individuals with one sickle-cell allele have increased resistance to malaria, a parasite
that spends part of its life cycle in red blood cells.
 In tropical Africa, where malaria is common, the sickle-cell allele is both a boon and a
 Homozygous normal individuals die of malaria and homozygous recessive
individuals die of sickle-cell disease, while carriers are relatively free of both.
 The relatively high frequency of sickle-cell trait in African-Americans is a vestige of their
African roots.
 Normally it is relatively unlikely that two carriers of the same rare, harmful allele will
meet and mate.
 However, consanguineous matings between close relatives increase the risk.
 Individuals who share a recent common ancestor are more likely to carry the same
recessive alleles.
 Most societies and cultures have laws or taboos forbidding marriages between close
 Although most harmful alleles are recessive, a number of human disorders are due to
dominant alleles.
 For example, achondroplasia, a form of dwarfism, has an incidence of one case in 25,000
 Heterozygous individuals have the dwarf phenotype.
 Those who are not achondroplastic dwarfs, 99.99% of the population, are homozygous
recessive for this trait.
 This provides another example of a trait for which the recessive allele is far more
prevalent than the dominant allele.
 Lethal dominant alleles are much less common than lethal recessives.
 If a lethal dominant kills an offspring before it can mature and reproduce, the allele
will not be passed on to future generations.
 In contrast, a lethal recessive allele can be passed on by heterozygous carriers who
have normal phenotypes.
 A lethal dominant allele can escape elimination if it causes death at a relatively advanced
age, after the individual has already passed on the lethal allele to his or her children.
 One example is Huntington’s disease, a degenerative disease of the nervous system.
 The dominant lethal allele has no obvious phenotypic effect until an individual is about
35 to 45 years old.
 The deterioration of the nervous system is irreversible and inevitably fatal.
 Any child born to a parent who has the allele for Huntington’s disease has a 50% chance
of inheriting the disease and the disorder.
 In the United States, this devastating disease afflicts one in 10,000 people.
 Recently, molecular geneticists have used pedigree analysis of affected families to track
the Huntington’s allele to a locus near the tip of chromosome 4.
 This has led to the development of a test that can detect the presence of the
Huntington’s allele in an individual’s genome.

Biology Chapter Notes

 While some diseases are inherited in a simple Mendelian fashion due to alleles at a single
locus, many other disorders have a multifactorial basis.
 These may have a genetic component plus a significant environmental influence.
 Multifactorial disorders include heart disease; diabetes; cancer; alcoholism; and certain
mental illnesses, such as schizophrenia and manic-depressive disorder.
 The genetic component of such disorders is typically polygenic.
 At present, little is understood about the genetic contribution to most multifactorial
 The best public health strategy is education about relevant environmental factors and
promotion of healthy behavior.
Technology is providing new tools for genetic testing and counseling.
 A preventive approach to simple Mendelian disorders is sometimes possible.
 The risk that a particular genetic disorder will occur can sometimes be assessed before a
child is conceived or early in pregnancy.
 Many hospitals have genetic counselors to provide information to prospective parents who
are concerned about a family history of a specific disease.
 Consider a hypothetical couple, John and Carol, who are planning to have their first child.
 In both of their families’ histories, a recessive lethal disorder is present. Both John and
Carol had brothers who died of the disease.
 While not one of John, Carol, or their parents have the disease, their parents must have
been carriers (Aa × Aa).
 John and Carol each have a 2/3 chance of being carriers and a 1/3 chance of being
homozygous dominant.
 The probability that their first child will have the disease is 2/3 (chance that John is a
carrier) × 2/3 (chance that Carol is a carrier) × 1/4 (chance that the offspring of two
carriers is homozygous recessive) = 1/9.
 If their first child is born with the disease, we know that John and Carol’s genotype
must be Aa and they are both carriers.
 In that case, the chance that their next child will also have the disease is 1/4.
 Mendel’s laws are simply the rules of probability applied to heredity.
 Because chance has no memory, the genotype of each child is unaffected by the
genotypes of older siblings.
 The chance that John and Carol’s first three children will have the disorder is 1/4 × 1/4
× 1/4 = 1/64. Should that outcome happen, the likelihood that a fourth child will also
have the disorder is still 1/4.
 Because most children with recessive disorders are born to parents with a normal
phenotype, the key to assessing risk is identifying whether prospective parents are carriers
of the recessive trait.
 Recently developed tests for several disorders can distinguish normal phenotypes in
heterozygotes from homozygous dominants.
 These results allow individuals with a family history of a genetic disorder to make
informed decisions about having children.
 However, issues of confidentiality, discrimination, and counseling may arise.
 Tests are also available to determine in utero if a child has a particular disorder.

Biology Chapter Notes

 One technique, amniocentesis, can be used from the 14th to 16th week of pregnancy to
assess whether the fetus has a specific disease.
 Fetal cells extracted from amniotic fluid are cultured and karyotyped to identify some
 Other disorders can be identified from chemicals in the amniotic fluids.
 A second technique, chorionic villus sampling (CVS) allows faster karyotyping and can
be performed as early as the eighth to tenth week of pregnancy.
 This technique extracts a sample of fetal tissue from the chorionic villi of the placenta.
 This technique is not suitable for tests requiring amniotic fluid.
 Other techniques, ultrasound and fetoscopy, allow fetal health to be assessed visually in
 Both fetoscopy and amniocentesis cause complications such as maternal bleeding or
fetal death in about 1% of cases.
 Therefore, these techniques are usually reserved for cases in which the risk of a genetic
disorder or other type of birth defect is relatively great.
 If fetal tests reveal a serious disorder, the parents face the difficult choice of terminating
the pregnancy or preparing to care for a child with a genetic disorder.
 Some genetic traits can be detected at birth by simple tests that are now routinely
performed in hospitals.
 One test can detect the presence of a recessively inherited disorder, phenylketonuria
 This disorder occurs in one in 10,000 to 15,000 births.
 Individuals with this disorder accumulate the amino acid phenylalanine and its
derivative phenylpyruvate in the blood to toxic levels.
 This leads to mental retardation.
 If the disorder is detected, a special diet low in phenylalanine usually promotes normal
 Unfortunately, few other genetic diseases are so treatable.

Biology Chapter Notes

Chapter 15 The Chromosomal Basis of Inheritance
Chapter Notes

Overview: Locating Genes on Chromosomes

 Today we know that genes—Gregor Mendel’s “hereditary factors”—are located on

 A century ago, the relationship of genes and chromosomes was not so obvious.
 Many biologists were skeptical about Mendel’s laws of segregation and independent
assortment until evidence mounted that they had a physical basis in the behavior of

Concept 15.1 Mendelian inheritance has its physical basis in the behavior of
 Around 1900, cytologists and geneticists began to see parallels between the behavior of
chromosomes and the behavior of Mendel’s factors.
 Using improved microscopy techniques, cytologists worked out the process of mitosis
in 1875 and meiosis in the 1890s.
 Chromosomes and genes are both present in pairs in diploid cells.
 Homologous chromosomes separate and alleles segregate during meiosis.
 Fertilization restores the paired condition for both chromosomes and genes.
 Around 1902, Walter Sutton, Theodor Boveri, and others noted these parallels and a
chromosome theory of inheritance began to take form:
 Genes occupy specific loci on chromosomes.
 Chromosomes undergo segregation during meiosis.
 Chromosomes undergo independent assortment during meiosis.
 The behavior of homologous chromosomes during meiosis can account for the
segregation of the alleles at each genetic locus to different gametes.
 The behavior of nonhomologous chromosomes can account for the independent
assortment of alleles for two or more genes located on different chromosomes.
Morgan traced a gene to a specific chromosome.
 In the early 20th century, Thomas Hunt Morgan was the first geneticist to associate a
specific gene with a specific chromosome.
 Like Mendel, Morgan made an insightful choice in his experimental animal. Morgan
worked with Drosophila melanogaster, a fruit fly that eats fungi on fruit.
 Fruit flies are prolific breeders and have a generation time of two weeks.
 Fruit flies have three pairs of autosomes and a pair of sex chromosomes (XX in
females, XY in males).
 Morgan spent a year looking for variant individuals among the flies he was breeding.
 He discovered a single male fly with white eyes instead of the usual red.
 The normal character phenotype is the wild type.

Biology Chapter Notes

 Alternative traits are called mutant phenotypes because they are due to alleles that
originate as mutations in the wild-type allele.
 When Morgan crossed his white-eyed male with a red-eyed female, all the F1 offspring
had red eyes, suggesting that the red allele was dominant to the white allele.
 Crosses between the F1 offspring produced the classic 3:1 phenotypic ratio in the F 2
 Surprisingly, the white-eyed trait appeared only in F2 males.
 All the F2 females and half the F2 males had red eyes.
 Morgan concluded that a fly’s eye color was linked to its sex.
 Morgan deduced that the gene with the white-eyed mutation is on the X chromosome,
with no corresponding allele present on the Y chromosome.
 Females (XX) may have two red-eyed alleles and have red eyes or may be
heterozygous and have red eyes.
 Males (XY) have only a single allele. They will be red-eyed if they have a red-eyed
allele or white-eyed if they have a white-eyed allele.

Concept 15.2 Linked genes tend to be inherited together because they are located near
each other on the same chromosome
 Each chromosome has hundreds or thousands of genes.
 Genes located on the same chromosome that tend to be inherited together are called
linked genes.
 Results of crosses with linked genes deviate from those expected according to
independent assortment.
 Morgan observed this linkage and its deviations when he followed the inheritance of
characters for body color and wing size.
 The wild-type body color is gray (b+), and the mutant is black (b).
 The wild-type wing size is normal (vg+), and the mutant has vestigial wings (vg).
 The mutant alleles are recessive to the wild-type alleles.
 Neither gene is on a sex chromosome.
 Morgan crossed F1 heterozygous females (b+bvg+vg) with homozygous recessive males
 According to independent assortment, this should produce 4 phenotypes in a 1:1:1:1 ratio.
 Surprisingly, Morgan observed a large number of wild-type (gray-normal) and double-
mutant (black-vestigial) flies among the offspring.
 These phenotypes are those of the parents.
 Morgan reasoned that body color and wing shape are usually inherited together because
the genes for these characters are on the same chromosome.
 The other two phenotypes (gray-vestigial and black-normal) were fewer than expected
from independent assortment (but totally unexpected from dependent assortment).
 What led to this genetic recombination, the production of offspring with new
combinations of traits?
Independent assortment of chromosomes and crossing over produce genetic
Biology Chapter Notes
 Genetic recombination can result from independent assortment of genes located on
nonhomologous chromosomes or from crossing over of genes located on homologous
 Mendel’s dihybrid cross experiments produced offspring that had a combination of traits
that did not match either parent in the P generation.
 If the P generation consists of a yellow-round seed parent (YYRR) crossed with a
green-wrinkled seed parent (yyrr), all F1 plants have yellow-round seeds (YyRr).
 A cross between an F1 plant and a homozygous recessive plant (a testcross) produces
four phenotypes.
 Half are the parental types, with phenotypes that match the original P parents, with
either yellow-round seeds or green-wrinkled seeds.
 Half are recombinants, new combinations of parental traits, with yellow-wrinkled or
green-round seeds.
 A 50% frequency of recombination is observed for any two genes located on different
(nonhomologous) chromosomes.
 The physical basis of recombination between unlinked genes is the random orientation of
homologous chromosomes at metaphase I of meiosis, which leads to the independent
assortment of alleles.
 The F1 parent (YyRr) produces gametes with four different combinations of alleles: YR,
Yr, yR, and yr.
 The orientation of the tetrad containing the seed-color gene has no bearing on the
orientation of the tetrad with the seed-shape gene.
 In contrast, linked genes, genes located on the same chromosome, tend to move together
through meiosis and fertilization.
 Under normal Mendelian genetic rules, we would not expect linked genes to recombine
into assortments of alleles not found in the parents.
 If the seed color and seed coat genes were linked, we would expect the F 1 offspring to
produce only two types of gametes, YR and yr, when the tetrads separate.
 One homologous chromosome carries the Y and R alleles on the same chromosome,
and the other homologous chromosome carries the y and r alleles.
 The results of Morgan’s testcross for body color and wing shape did not conform to either
independent assortment or complete linkage.
 Under independent assortment, the testcross should produce a 1:1:1:1 phenotypic ratio.
 If completely linked, we should expect to see a 1:1:0:0 ratio with only parental
phenotypes among offspring.
 Most of the offspring had parental phenotypes, suggesting linkage between the genes.
 However, 17% of the flies were recombinants, suggesting incomplete linkage.
 Morgan proposed that some mechanism must occasionally break the physical connection
between genes on the same chromosome.
 This process, called crossing over, accounts for the recombination of linked genes.
 Crossing over occurs while replicated homologous chromosomes are paired during
prophase of meiosis I.
 One maternal and one paternal chromatid break at corresponding points and then rejoin
with each other.
 The occasional production of recombinant gametes during meiosis accounts for the
occurrence of recombinant phenotypes in Morgan’s testcross.
Biology Chapter Notes
 The percentage of recombinant offspring, the recombination frequency, is related to the
distance between linked genes.
Geneticists can use recombination data to map a chromosome’s genetic loci.
 One of Morgan’s students, Alfred Sturtevant, used crossing over of linked genes to
develop a method for constructing a genetic map, an ordered list of the genetic loci along
a particular chromosome.
 Sturtevant hypothesized that the frequency of recombinant offspring reflected the distance
between genes on a chromosome.
 He assumed that crossing over is a random event, and that the chance of crossing over is
approximately equal at all points on a chromosome.
 Sturtevant predicted that the farther apart two genes are, the higher the probability that a
crossover will occur between them, and therefore, the higher the recombination
 The greater the distance between two genes, the more points there are between them
where crossing over can occur.
 Sturtevant used recombination frequencies from fruit fly crosses to map the relative
position of genes along chromosomes.
 A genetic map based on recombination frequencies is called a linkage map.
 Sturtevant used the testcross design to map the relative position of three fruit fly genes,
body color (b), wing size (vg), and eye color (cn).
 The recombination frequency between cn and b is 9%.
 The recombination frequency between cn and vg is 9.5%.
 The recombination frequency between b and vg is 17%.
 The only possible arrangement of these three genes places the eye color gene between
the other two.
 Sturtevant expressed the distance between genes, the recombination frequency, as map
 One map unit (called a centimorgan) is equivalent to a 1% recombination frequency.
 You may notice that the three recombination frequencies in our mapping example are not
quite additive: 9% (b-cn) + 9.5% (cn-vg) > 17% (b-vg).
 This results from multiple crossing over events.
 A second crossing over “cancels out” the first and reduces the observed number of
recombinant offspring.
 Genes father apart (for example, b-vg) are more likely to experience multiple crossing
over events.
 Some genes on a chromosome are so far apart that a crossover between them is virtually
 In this case, the frequency of recombination reaches its maximum value of 50% and the
genes behave as if found on separate chromosomes.
 In fact, two genes studied by Mendel—for seed color and flower color—are located on
the same chromosome but still assort independently.
 Genes located far apart on a chromosome are mapped by adding the recombination
frequencies between the distant genes and the intervening genes.
 Sturtevant and his colleagues were able to map the linear positions of genes in Drosophila
into four groups, one for each chromosome.
Biology Chapter Notes
 A linkage map provides an imperfect picture of a chromosome.
 Map units indicate relative distance and order, not precise locations of genes.
 The frequency of crossing over is not actually uniform over the length of a
 A linkage map does portray the order of genes along a chromosome, but does not
accurately portray the precise location of those genes.
 Combined with other methods like chromosomal banding, geneticists can develop
cytogenetic maps of chromosomes.
 These indicate the positions of genes with respect to chromosomal features.
 Recent techniques show the physical distances between gene loci in DNA nucleotides.

Concept 15.3 Sex-linked genes exhibit unique patterns of inheritance

The chromosomal basis of sex varies with the organism.
 Although the anatomical and physiological differences between women and men are
numerous, the chromosomal basis of sex is rather simple.
 In humans and other mammals, there are two varieties of sex chromosomes, X and Y.
 An individual who inherits two X chromosomes usually develops as a female.
 An individual who inherits an X and a Y chromosome usually develops as a male.
 Other animals have different methods of sex determination.
 The X-0 system is found in some insects. Females are XX, males are X.
 In birds, some fishes, and some insects, females are ZW and males are ZZ.
 In bees and ants, females are diploid and males are haploid.
 In the X-Y system, the Y chromosome is much smaller than the X chromosome.
 Only relatively short segments at either end of the Y chromosome are homologous with
the corresponding regions of the X chromosome.
 The X and Y rarely cross over.
 In both testes (XY) and ovaries (XX), the two sex chromosomes segregate during meiosis,
and each gamete receives one.
 Each ovum receives an X chromosome.
 Half the sperm cells receive an X chromosome, and half receive a Y chromosome.
 Because of this, each conception has about a fifty-fifty chance of producing a particular
 If a sperm cell bearing an X chromosome fertilizes an ovum, the resulting zygote is
female (XX).
 If a sperm cell bearing a Y chromosome fertilizes an ovum, the resulting zygote is
male (XY).
 In humans, the anatomical signs of sex first appear when the embryo is about two months
 In 1990, a British research team identified a gene on the Y chromosome required for the
development of testes.
 They named the gene SRY (sex-determining region of the Y chromosome).
 In individuals with the SRY gene, the generic embryonic gonads develop into testes.
Biology Chapter Notes
 Activity of the SRY gene triggers a cascade of biochemical, physiological, and
anatomical features because it regulates many other genes.
 Other genes on the Y chromosome are necessary for the production of functional
 In the absence of these genes, an XY individual is male but does not produce normal
 In individuals lacking the SRY gene, the generic embryonic gonads develop into ovaries.
Sex-linked genes have unique patterns of inheritance.
 In addition to their role in determining sex, the sex chromosomes, especially the X
chromosome, have genes for many characters unrelated to sex.
 A gene located on either sex chromosome is called a sex-linked gene.
 In humans, the term refers to a gene on the X chromosome.
 Human sex-linked genes follow the same pattern of inheritance as Morgan’s white-eye
locus in Drosophila.
 Fathers pass sex-linked alleles to all their daughters but none of their sons.
 Mothers pass sex-linked alleles to both sons and daughters.
 If a sex-linked trait is due to a recessive allele, a female will express this phenotype only
if she is homozygous.
 Heterozygous females are carriers for the recessive trait.
 Because males have only one X chromosome (hemizygous), any male receiving the
recessive allele from his mother will express the recessive trait.
 The chance of a female inheriting a double dose of the mutant allele is much less than
the chance of a male inheriting a single dose.
 Therefore, males are far more likely to exhibit sex-linked recessive disorders than are
 For example, color blindness is a mild disorder inherited as a sex-linked trait.
 A color-blind daughter may be born to a color-blind father whose mate is a carrier.
 However, the odds of this are fairly low.
 Several serious human disorders are sex-linked.
 Duchenne muscular dystrophy affects one in 3,500 males born in the United States.
 Affected individuals rarely live past their early 20s.
 This disorder is due to the absence of an X-linked gene for a key muscle protein called
 The disease is characterized by a progressive weakening of the muscles and a loss of
 Hemophilia is a sex-linked recessive disorder defined by the absence of one or more
proteins required for blood clotting.
 These proteins normally slow and then stop bleeding.
 Individuals with hemophilia have prolonged bleeding because a firm clot forms
 Bleeding in muscles and joints can be painful and can lead to serious damage.
 Today, people with hemophilia can be treated with intravenous injections of the missing

Biology Chapter Notes

 Although female mammals inherit two X chromosomes, only one X chromosome is
 Therefore, males and females have the same effective dose (one copy) of genes on the X
 During female development, one X chromosome per cell condenses into a compact
object called a Barr body.
 Most of the genes on the Barr-body chromosome are not expressed.
 The condensed Barr-body chromosome is reactivated in ovarian cells that produce ova.
 Mary Lyon, a British geneticist, demonstrated that selection of which X chromosome will
form the Barr body occurs randomly and independently in embryonic cells at the time of
X inactivation.
 As a consequence, females consist of a mosaic of two types of cells, some with an active
paternal X chromosome, others with an active maternal X chromosome.
 After an X chromosome is inactivated in a particular cell, all mitotic descendants of
that cell will have the same inactive X.
 If a female is heterozygous for a sex-linked trait, approximately half her cells will
express one allele, and the other half will express the other allele.
 In humans, this mosaic pattern is evident in women who are heterozygous for an X-linked
mutation that prevents the development of sweat glands.
 A heterozygous woman will have patches of normal skin and skin patches lacking
sweat glands.
 Similarly, the orange-and-black pattern on tortoiseshell cats is due to patches of cells
expressing an orange allele while other patches have a nonorange allele.
 X inactivation involves modification of the DNA by attachment of methyl (—CH3)
groups to cytosine nucleotides on the X chromosome that will become the Barr body.
 Researchers have discovered a gene called XIST (X-inactive specific transcript).
 This gene is active only on the Barr-body chromosome and produces multiple copies of
an RNA molecule that attach to the X chromosome on which they were made.
 This initiates X inactivation.
 The mechanism that connects XIST RNA and DNA methylation is unknown.
 What determines which of the two X chromosomes has an active XIST gene is also

Concept 15.4 Alterations of chromosome number or structure cause some genetic

 Physical and chemical disturbances can damage chromosomes in major ways.
 Errors during meiosis can alter chromosome number in a cell.
 Plants tolerate genetic defects to a greater extent that do animals.
 Nondisjunction occurs when problems with the meiotic spindle cause errors in daughter
 This may occur if tetrad chromosomes do not separate properly during meiosis I.
 Alternatively, sister chromatids may fail to separate during meiosis II.

Biology Chapter Notes

 As a consequence of nondisjunction, one gamete receives two of the same type of
chromosome, and another gamete receives no copy.
 Offspring resulting from fertilization of a normal gamete with one produced by
nondisjunction will have an abnormal chromosome number, a condition known as
 Trisomic cells have three copies of a particular chromosome type and have 2n + 1
total chromosomes.
 Monosomic cells have only one copy of a particular chromosome type and have 2n − 1
 If the organism survives, aneuploidy typically leads to a distinct phenotype.
 Aneuploidy can also occur during failures of the mitotic spindle.
 If this happens early in development, the aneuploid condition will be passed along by
mitosis to a large number of cells.
 This is likely to have a substantial effect on the organism.
 Organisms with more than two complete sets of chromosomes are polyploid.
 This may occur when a normal gamete fertilizes another gamete in which there has been
nondisjunction of all its chromosomes.
 The resulting zygote would be triploid (3n).
 Alternatively, if a 2n zygote failed to divide after replicating its chromosomes, a
tetraploid (4n) embryo would result from subsequent successful cycles of mitosis.
 Polyploidy is relatively common among plants and much less common among animals,
although it is known to occur in fishes and amphibians.
 The spontaneous origin of polyploid individuals plays an important role in the
evolution of plants.
 Both fishes and amphibians have polyploid species.
 Recently, researchers in Chile have identified a new rodent species that may be
 Polyploids are more nearly normal in phenotype than aneuploids.
 One extra or missing chromosome apparently upsets the genetic balance during
development more than does an entire extra set of chromosomes.
 Breakage of a chromosome can lead to four types of changes in chromosome structure.
 A deletion occurs when a chromosome fragment lacking a centromere is lost during
cell division.
 This chromosome will be missing certain genes.
 A duplication occurs when a fragment becomes attached as an extra segment to a
sister chromatid.
 Alternatively, a detached fragment may attach to a nonsister chromatid of a
homologous chromosome.
 In this case, the duplicated segments will not be identical if the homologues carry
different alleles.
 An inversion occurs when a chromosomal fragment reattaches to the original
chromosome, but in the reverse orientation.
 In translocation, a chromosomal fragment joins a nonhomologous chromosome.
 Deletions and duplications are especially likely to occur during meiosis.

Biology Chapter Notes

 Homologous chromatids may break and rejoin at incorrect places during crossing over,
so that one chromatid loses more genes than it receives.
 The products of such a nonreciprocal crossover are one chromosome with a deletion
and one chromosome with a duplication.
 A diploid embryo that is homozygous for a large deletion or a male with a large deletion
to its single X chromosome is usually missing many essential genes.
 This is usually lethal.
 Duplications and translocations are typically harmful.
 Reciprocal translocation or inversion can alter phenotype because a gene’s expression is
influenced by its location among neighboring genes.
Human disorders are due to chromosome alterations.
 Several serious human disorders are due to alterations of chromosome number and
 Although the frequency of aneuploid zygotes may be quite high in humans, most of these
alterations are so disastrous to development that the embryos are spontaneously aborted
long before birth.
 Severe developmental problems result from an imbalance among gene products.
 Certain aneuploid conditions upset the balance less, making survival to birth and beyond
 Surviving individuals have a set of symptoms—a syndrome—characteristic of the type
of aneuploidy.
 Genetic disorders caused by aneuploidy can be diagnosed before birth by fetal testing.
 One aneuploid condition, Down syndrome, is due to three copies of chromosome 21 or
trisomy 21.
 It affects one in 700 children born in the United States.
 Although chromosome 21 is the smallest human chromosome, trisomy 21 severely alters
an individual’s phenotype in specific ways.
 Individuals with Down syndrome have characteristic facial features, short stature, heart
defects, susceptibility to respiratory infection, mental retardation, and increased risk of
developing leukemia and Alzheimer’s disease.
 Most are sexually underdeveloped and sterile.
 Most cases of Down syndrome result from nondisjunction during gamete production in
one parent.
 The frequency of Down syndrome increases with the age of the mother.
 This may be linked to some age-dependent abnormality in the spindle checkpoint
during meiosis I, leading to nondisjunction.
 Trisomies of other chromosomes also increase in incidence with maternal age, but it is
rare for infants with these autosomal trisomies to survive for long.
 Nondisjunction of sex chromosomes produces a variety of aneuploid conditions in
 This aneuploidy upsets the genetic balance less severely that autosomal aneuploidy.
 This may be because the Y chromosome contains relatively few genes and because
extra copies of the X chromosome become inactivated as Barr bodies in somatic cells.
 An XXY male has Klinefelter’s syndrome, which occurs once in every 2,000 live births.
Biology Chapter Notes
 These individuals have male sex organs, but have abnormally small testes and are
 Although the extra X is inactivated, some breast enlargement and other female
characteristics are common.
 Affected individuals have normal intelligence.
 Males with an extra Y chromosome (XYY) tend to be somewhat taller than average.
 Trisomy X (XXX), which occurs once in every 2,000 live births, produces healthy
 Monosomy X or Turner syndrome (X0) occurs once in every 5,000 births.
 This is the only known viable monosomy in humans.
 X0 individuals are phenotypically female but are sterile because their sex organs do
not mature.
 When provided with estrogen replacement therapy, girls with Turner syndrome
develop secondary sex characteristics.
 Most are of normal intelligence.
 Structural alterations of chromosomes can also cause human disorders.
 Deletions, even in a heterozygous state, can cause severe problems.
 One syndrome, cri du chat, results from a specific deletion in chromosome 5.
 These individuals are mentally retarded, have small heads with unusual facial features,
and have a cry like the mewing of a distressed cat.
 This syndrome is fatal in infancy or early childhood.
 Chromosomal translocations between nonhomologous chromosomes are also associated
with human disorders.
 Chromosomal translocations have been implicated in certain cancers, including chronic
myelogenous leukemia (CML).
 CML occurs when a large fragment of chromosome 22 switches places with a small
fragment from the tip of chromosome 9.
 The resulting short, easily recognized chromosome 22 is called the Philadelphia

Concept 15.5 Some inheritance patterns are exceptions to the standard chromosome
The phenotypic effects of some mammalian genes depend on whether they are inherited
from the mother or the father.
 For most genes, it is a reasonable assumption that a specific allele will have the same
effect regardless of whether it is inherited from the mother or father.
 However, for a few dozen mammalian traits, phenotype varies depending on which parent
passed along the alleles for those traits.
 The genes involved are not necessarily sex linked and may or may not lie on the X
 Variation in phenotype depending on whether an allele is inherited from the male or
female parent is called genomic imprinting.
 Genomic imprinting occurs during formation of gametes and results in the silencing of
certain genes.
Biology Chapter Notes
 Imprinted genes are not expressed.
 Because different genes are imprinted in sperm and ova, some genes in a zygote are
maternally imprinted, and others are paternally imprinted.
 These maternal and paternal imprints are transmitted to all body cells during
 For a maternally imprinted gene, only the paternal allele is expressed.
 For a paternally imprinted gene, only the maternal allele is expressed.
 Patterns of imprinting are characteristic of a given species.
 The gene for insulin-like growth factor 2 (Igf2) is one of the first imprinted genes to be
 Although the growth factor is required for normal prenatal growth, only the paternal allele
is expressed.
 Evidence that the Igf2 allele is imprinted initially came from crosses between wild-type
mice and dwarf mice homozygous for a recessive mutation in the Igf2 gene.
 The phenotypes of heterozygous offspring differ, depending on whether the mutant
allele comes from the mother or the father.
 The Igf2 allele is imprinted in eggs, turning off expression of the imprinted allele.
 In sperm, the Igf2 allele is not imprinted and functions normally.
 What exactly is a genomic imprint?
 In many cases, it consists of methyl (—CH3) groups that are added to the cytosine
nucleotides of one of the alleles.
 The hypothesis that methylation directly silences an allele is consistent with the evidence
that heavily methylated genes are usually inactive.
 Other mechanisms may lead to silencing of imprinted genes.
 Most of the known imprinted genes are critical for embryonic development.
 In experiments with mice, embryos engineered to inherit both copies of certain
chromosomes from the same parent die before birth, whether their lone parent is male or
 Normal development requires that embryonic cells have one active copy of certain genes.
 Aberrant imprinting is associated with abnormal development and certain cancers.
Extranuclear genes exhibit a non-Mendelian pattern of inheritance.
 Not all of a eukaryote cell’s genes are located on nuclear chromosomes, or even in the
 Extranuclear genes are found in small circles of DNA in mitochondria and chloroplasts.
 These organelles reproduce themselves and transmit their genes to daughter organelles.
 Their cytoplasmic genes do not display Mendelian inheritance, because they are not
distributed to offspring according to the same rules that direct distribution of nuclear
chromosomes during meiosis.
 Karl Correns first observed cytoplasmic genes in plants in 1909 when he studied the
inheritance of patches of yellow or white on the leaves of an otherwise green plant.
 He determined that the coloration of the offspring was determined by only the maternal

Biology Chapter Notes

 These coloration patterns are due to genes in the plastids that are inherited only via the
ovum, not via the sperm nucleus in the pollen.
 Because a zygote inherits all its mitochondria from the ovum, all mitochondrial genes in
mammals demonstrate maternal inheritance.
 Several rare human disorders are produced by mutations to mitochondrial DNA.
 These primarily impact ATP supply by producing defects in the electron transport
chain or ATP synthase.
 Tissues that require high energy supplies (the nervous system and muscles) may suffer
energy deprivation from these defects.
 For example, a person with mitochondrial myopathy suffers weakness, intolerance of
exercise, and muscle deterioration.
 Other mitochondrial mutations may contribute to diabetes, heart disease, and other
diseases of aging.

Biology Chapter Notes

Chapter 16 The Molecular Basis of Inheritance
Chapter Notes

Overview: Life’s Operating Instructions

 In April 1953, James Watson and Francis Crick shook the scientific world with an elegant
double-helical model for the structure of deoxyribonucleic acid, or DNA.
 Your genetic endowment is the DNA you inherited from your parents.
 Nucleic acids are unique in their ability to direct their own replication.
 The resemblance of offspring to their parents depends on the precise replication of DNA
and its transmission from one generation to the next.
 It is this DNA program that directs the development of your biochemical, anatomical,
physiological, and (to some extent) behavioral traits.

Concept 16.1 DNA is the genetic material

The search for genetic material led to DNA.
 Once T. H. Morgan’s group showed that genes are located on chromosomes, the two
constituents of chromosomes—proteins and DNA—were the candidates for the genetic
 Until the 1940s, the great heterogeneity and specificity of function of proteins seemed to
indicate that proteins were the genetic material.
 However, this was not consistent with experiments with microorganisms, such as bacteria
and viruses.
 The discovery of the genetic role of DNA began with research by Frederick Griffith in
 He studied Streptococcus pneumoniae, a bacterium that causes pneumonia in mammals.
 One strain, the R strain, was harmless.
 The other strain, the S strain, was pathogenic.
 Griffith mixed heat-killed S strain with live R strain bacteria and injected this into a
 The mouse died, and he recovered the pathogenic strain from the mouse’s blood.
 Griffith called this phenomenon transformation, a phenomenon now defined as a change
in genotype and phenotype due to the assimilation of foreign DNA by a cell.
 For the next 14 years, scientists tried to identify the transforming substance.
 Finally in 1944, Oswald Avery, Maclyn McCarty, and Colin MacLeod announced that the
transforming substance was DNA.
 Still, many biologists were skeptical.
 Proteins were considered better candidates for the genetic material.
 There was also a belief that the genes of bacteria could not be similar in composition
and function to those of more complex organisms.
Biology Chapter Notes
 Further evidence that DNA was the genetic material was derived from studies that tracked
the infection of bacteria by viruses.
 Viruses consist of DNA (or sometimes RNA) enclosed by a protective coat of protein.
 To replicate, a virus infects a host cell and takes over the cell’s metabolic machinery.
 Viruses that specifically attack bacteria are called bacteriophages or just phages.
 In 1952, Alfred Hershey and Martha Chase showed that DNA was the genetic material of
the phage T2.
 The T2 phage, consisting almost entirely of DNA and protein, attacks Escherichia coli (E.
coli), a common intestinal bacteria of mammals.
 This phage can quickly turn an E. coli cell into a T2-producing factory that releases
phages when the cell ruptures.
 To determine the source of genetic material in the phage, Hershey and Chase designed an
experiment in which they could label protein or DNA and then track which entered the E.
coli cell during infection.
 They grew one batch of T2 phage in the presence of radioactive sulfur, marking the
proteins but not DNA.
 They grew another batch in the presence of radioactive phosphorus, marking the DNA
but not proteins.
 They allowed each batch to infect separate E. coli cultures.
 Shortly after the onset of infection, they spun the cultured infected cells in a blender,
shaking loose any parts of the phage that remained outside the bacteria.
 The mixtures were spun in a centrifuge, which separated the heavier bacterial cells in
the pellet from lighter free phages and parts of phage in the liquid supernatant.
 They then tested the pellet and supernatant of the separate treatments for the presence
of radioactivity.
 Hershey and Chase found that when the bacteria had been infected with T2 phages that
contained radiolabeled proteins, most of the radioactivity was in the supernatant that
contained phage particles, not in the pellet with the bacteria.
 When they examined the bacterial cultures with T2 phage that had radiolabeled DNA,
most of the radioactivity was in the pellet with the bacteria.
 Hershey and Chase concluded that the injected DNA of the phage provides the genetic
information that makes the infected cells produce new viral DNA and proteins to
assemble into new viruses.
 The fact that cells double the amount of DNA in a cell prior to mitosis and then distribute
the DNA equally to each daughter cell provided some circumstantial evidence that DNA
was the genetic material in eukaryotes.
 Similar circumstantial evidence came from the observation that diploid sets of
chromosomes have twice as much DNA as the haploid sets in gametes of the same
 By 1947, Erwin Chargaff had developed a series of rules based on a survey of DNA
composition in organisms.
 He already knew that DNA was a polymer of nucleotides consisting of a nitrogenous
base, deoxyribose, and a phosphate group.
 The bases could be adenine (A), thymine (T), guanine (G), or cytosine (C).
 Chargaff noted that the DNA composition varies from species to species.

Biology Chapter Notes

 In any one species, the four bases are found in characteristic, but not necessarily equal,
 He also found a peculiar regularity in the ratios of nucleotide bases that are known as
Chargaff’s rules.
 In all organisms, the number of adenines was approximately equal to the number of
thymines (%T = %A).
 The number of guanines was approximately equal to the number of cytosines (%G = %C).
 Human DNA is 30.9% adenine, 29.4% thymine, 19.9% guanine, and 19.8% cytosine.
 The basis for these rules remained unexplained until the discovery of the double helix.
Watson and Crick discovered the double helix by building models to conform to X-ray
 By the beginnings of the 1950s, the race was on to move from the structure of a single
DNA strand to the three-dimensional structure of DNA.
 Among the scientists working on the problem were Linus Pauling in California and
Maurice Wilkins and Rosalind Franklin in London.
 Maurice Wilkins and Rosalind Franklin used X-ray crystallography to study the structure
of DNA.
 In this technique, X-rays are diffracted as they passed through aligned fibers of
purified DNA.
 The diffraction pattern can be used to deduce the three-dimensional shape of
 James Watson learned from their research that DNA was helical in shape, and he deduced
the width of the helix and the spacing of nitrogenous bases.
 The width of the helix suggested that it was made up of two strands, contrary to a
three-stranded model that Linus Pauling had recently proposed.
 Watson and his colleague Francis Crick began to work on a model of DNA with two
strands, the double helix.
 Using molecular models made of wire, they placed the sugar-phosphate chains on the
outside and the nitrogenous bases on the inside of the double helix.
 This arrangement put the relatively hydrophobic nitrogenous bases in the molecule’s
 The sugar-phosphate chains of each strand are like the side ropes of a rope ladder.
 Pairs of nitrogenous bases, one from each strand, form rungs.
 The ladder forms a twist every ten bases.
 The nitrogenous bases are paired in specific combinations: adenine with thymine and
guanine with cytosine.
 Pairing like nucleotides did not fit the uniform diameter indicated by the X-ray data.
 A purine-purine pair is too wide, and a pyrimidine-pyrimidine pairing is too short.
 Only a pyrimidine-purine pairing produces the 2-nm diameter indicated by the X-ray
 In addition, Watson and Crick determined that chemical side groups of the nitrogenous
bases would form hydrogen bonds, connecting the two strands.
 Based on details of their structure, adenine would form two hydrogen bonds only with
thymine, and guanine would form three hydrogen bonds only with cytosine.
Biology Chapter Notes
 This finding explained Chargaff’s rules.
 The base-pairing rules dictate the combinations of nitrogenous bases that form the “rungs”
of DNA.
 However, this does not restrict the sequence of nucleotides along each DNA strand.
 The linear sequence of the four bases can be varied in countless ways.
 Each gene has a unique order of nitrogenous bases.
 In April 1953, Watson and Crick published a succinct, one-page paper in Nature reporting
their double helix model of DNA.

Concept 16.2 Many proteins work together in DNA replication and repair
 The specific pairing of nitrogenous bases in DNA was the flash of inspiration that led
Watson and Crick to the correct double helix.
 The possible mechanism for the next step, the accurate replication of DNA, was clear to
Watson and Crick from their double helix model.
During DNA replication, base pairing enables existing DNA strands to serve as templates
for new complementary strands.
 In a second paper, Watson and Crick published their hypothesis for how DNA replicates.
 Essentially, because each strand is complementary to the other, each can form a
template when separated.
 The order of bases on one strand can be used to add complementary bases and
therefore duplicate the pairs of bases exactly.
 When a cell copies a DNA molecule, each strand serves as a template for ordering
nucleotides into a new complementary strand.
 One at a time, nucleotides line up along the template strand according to the base-
pairing rules.
 The nucleotides are linked to form new strands.
 Watson and Crick’s model, semiconservative replication, predicts that when a double
helix replicates, each of the daughter molecules will have one old strand and one newly
made strand.
 Other competing models, the conservative model and the dispersive model, were also
 Experiments in the late 1950s by Matthew Meselson and Franklin Stahl supported the
semiconservative model proposed by Watson and Crick over the other two models.
 In their experiments, 15they labeled the nucleotides of the old strands with a heavy
isotope of nitrogen ( N), while any new nucleotides were indicated by a lighter
isotope (14N).
 Replicated strands could be separated by density in a centrifuge.
 Each model—the semiconservative model, the conservative model, and the dispersive
model—made specific predictions about the density of replicated DNA strands.
 The first replication in the 14N medium produced a band of hybrid (15N-14N) DNA,
eliminating the conservative model.
 A second replication produced both light and hybrid DNA, eliminating the dispersive
model and supporting the semiconservative model.
Biology Chapter Notes
A large team of enzymes and other proteins carries out DNA replication.
 It takes E. coli 25 minutes to copy each of the 5 million base pairs in its single
chromosome and divide to form two identical daughter cells.
 A human cell can copy its 6 billion base pairs and divide into daughter cells in only a few
 This process is remarkably accurate, with only one error per ten billion nucleotides.
 More than a dozen enzymes and other proteins participate in DNA replication.
 Much more is known about replication in bacteria than in eukaryotes.
 The process appears to be fundamentally similar for prokaryotes and eukaryotes.
 The replication of a DNA molecule begins at special sites, origins of replication.
 In bacteria, this is a specific sequence of nucleotides that is recognized by the replication
 These enzymes separate the strands, forming a replication “bubble.”
 Replication proceeds in both directions until the entire molecule is copied.
 In eukaryotes, there may be hundreds or thousands of origin sites per chromosome.
 At the origin sites, the DNA strands separate, forming a replication “bubble” with
replication forks at each end.
 The replication bubbles elongate as the DNA is replicated, and eventually fuse.
 DNA polymerases catalyze the elongation of new DNA at a replication fork.
 As nucleotides align with complementary bases along the template strand, they are added
to the growing end of the new strand by the polymerase.
 The rate of elongation is about 500 nucleotides per second in bacteria and 50 per
second in human cells.
 In E. coli, two different DNA polymerases are involved in replication: DNA polymerase
III and DNA polymerase I.
 In eukaryotes, at least 11 different DNA polymerases have been identified so far.
 Each nucleotide that is added to a growing DNA strand is a nucleoside triphosphate.
 Each has a nitrogenous base, deoxyribose, and a triphosphate tail.
 ATP is a nucleoside triphosphate with ribose instead of deoxyribose.
 Like ATP, the triphosphate monomers used for DNA synthesis are chemically reactive,
partly because their triphosphate tails have an unstable cluster of negative charge.
 As each nucleotide is added to the growing end of a DNA strand, the last two phosphate
groups are hydrolyzed to form pyrophosphate.
 The exergonic hydrolysis of pyrophosphate to two inorganic phosphate molecules
drives the polymerization of the nucleotide to the new strand.
 The strands in the double helix are antiparallel.
 The sugar-phosphate backbones run in opposite directions.
 Each DNA strand has a 3’ end with a free hydroxyl group attached to deoxyribose and
a 5’ end with a free phosphate group attached to deoxyribose.
 The 5’  3’ direction of one strand runs counter to the 3’  5’ direction of the other
 DNA polymerases can only add nucleotides to the free 3’ end of a growing DNA strand.
 A new DNA strand can only elongate in the 5’  3’ direction.
Biology Chapter Notes
 Along one template strand, DNA polymerase III can synthesize a complementary strand
continuously by elongating the new DNA in the mandatory 5’  3’ direction.
 The DNA strand made by this mechanism is called the leading strand.
 The other parental strand (5’  3’ into the fork), the lagging strand, is copied away from
the fork.
 Unlike the leading strand, which elongates continuously, the lagging stand is
synthesized as a series of short segments called Okazaki fragments.
 Okazaki fragments are about 1,000–2,000 nucleotides long in E. coli and 100–200
nucleotides long in eukaryotes.
 Another enzyme, DNA ligase, eventually joins the sugar-phosphate backbones of the
Okazaki fragments to form a single DNA strand.
 DNA polymerases cannot initiate synthesis of a polynucleotide.
 They can only add nucleotides to the 3’ end of an existing chain that is base-paired
with the template strand.
 The initial nucleotide chain is called a primer.
 In the initiation of the replication of cellular DNA, the primer is a short stretch of RNA
with an available 3’ end.
 The primer is 5–10 nucleotides long in eukaryotes.
 Primase, an RNA polymerase, links ribonucleotides that are complementary to the DNA
template into the primer.
 RNA polymerases can start an RNA chain from a single template strand.
 After formation of the primer, DNA pol III adds a deoxyribonucleotide to the 3’ end of
the RNA primer and continues adding DNA nucleotides to the growing DNA strand
according to the base-pairing rules.
 Returning to the original problem at the replication fork, the leading strand requires the
formation of only a single primer as the replication fork continues to separate.
 For synthesis of the lagging strand, each Okazaki fragment must be primed separately.
 Another DNA polymerase, DNA polymerase I, replaces the RNA nucleotides of the
primers with DNA versions, adding them one by one onto the 3’ end of the adjacent
Okazaki fragment.
 The primers are converted to DNA before DNA ligase joins the fragments together.
 In addition to primase, DNA polymerases, and DNA ligases, several other proteins have
prominent roles in DNA synthesis.
 Helicase untwists the double helix and separates the template DNA strands at the
replication fork.
 This untwisting causes tighter twisting ahead of the replication fork, and
topoisomerase helps relieve this strain.
 Single-strand binding proteins keep the unpaired template strands apart during
 To summarize, at the replication fork, the leading strand is copied continuously into the
fork from a single primer.
 The lagging strand is copied away from the fork in short segments, each requiring a
new primer.
 It is conventional and convenient to think of the DNA polymerase molecules as moving
along a stationary DNA template.
Biology Chapter Notes
 In reality, the various proteins involved in DNA replication form a single large complex, a
DNA replication “machine.”
 Many protein-protein interactions facilitate the efficiency of this machine.
 For example, helicase works much more rapidly when it is in contact with primase.
 The DNA replication machine is probably stationary during the replication process.
 In eukaryotic cells, multiple copies of the machine may anchor to the nuclear matrix, a
framework of fibers extending through the interior of the nucleus.
 The DNA polymerase molecules “reel in” the parental DNA and “extrude” newly made
daughter DNA molecules.
Enzymes proofread DNA during its replication and repair damage in existing DNA.
 Mistakes during the initial pairing of template nucleotides and complementary nucleotides
occur at a rate of one error per 100,000 base pairs.
 DNA polymerase proofreads each new nucleotide against the template nucleotide as soon
as it is added.
 If there is an incorrect pairing, the enzyme removes the wrong nucleotide and then
resumes synthesis.
 The final error rate is only one per ten billion nucleotides.
 DNA molecules are constantly subject to potentially harmful chemical and physical
 Reactive chemicals, radioactive emissions, X-rays, and ultraviolet light can change
nucleotides in ways that can affect encoded genetic information.
 DNA bases may undergo spontaneous chemical changes under normal cellular
 Mismatched nucleotides that are missed by DNA polymerase or mutations that occur after
DNA synthesis is completed can often be repaired.
 Each cell continually monitors and repairs its genetic material, with 100 repair
enzymes known in E. coli and more than 130 repair enzymes identified in humans.
 In mismatch repair, special enzymes fix incorrectly paired nucleotides.
 A hereditary defect in one of these enzymes is associated with a form of colon cancer.
 In nucleotide excision repair, a nuclease cuts out a segment of a damaged strand.
 DNA polymerase and ligase fill in the gap.
 The importance of the proper functioning of repair enzymes is clear from the inherited
disorder xeroderma pigmentosum.
 These individuals are hypersensitive to sunlight.
 Ultraviolet light can produce thymine dimers between adjacent thymine nucleotides.
 This buckles the DNA double helix and interferes with DNA replication.
 In individuals with this disorder, mutations in their skin cells are left uncorrected and
cause skin cancer.
The ends of DNA molecules are replicated by a special mechanism.
 Limitations of DNA polymerase create problems for the linear DNA of eukaryotic
 The usual replication machinery provides no way to complete the 5’ ends of daughter
DNA strands.
Biology Chapter Notes
 Repeated rounds of replication produce shorter and shorter DNA molecules.
 Prokaryotes do not have this problem because they have circular DNA molecules without
 The ends of eukaryotic chromosomal DNA molecules, the telomeres, have special
nucleotide sequences.
 Telomeres do not contain genes. Instead, the DNA typically consists of multiple
repetitions of one short nucleotide sequence.
 In human telomeres, this sequence is typically TTAGGG, repeated between 100 and
1,000 times.
 Telomeres protect genes from being eroded through multiple rounds of DNA replication.
 Telomeric DNA tends to be shorter in dividing somatic cells of older individuals and
in cultured cells that have divided many times.
 It is possible that the shortening of telomeres is somehow connected with the aging
process of certain tissues and perhaps to aging in general.
 Telomeric DNA and specific proteins associated with it also prevents the staggered ends
of the daughter molecule from activating the cell’s system for monitoring DNA damage.
 Eukaryotic cells have evolved a mechanism to restore shortened telomeres in germ cells,
which give rise to gametes.
 If the chromosomes of germ cells became shorter with every cell cycle, essential genes
would eventually be lost.
 An enzyme called telomerase catalyzes the lengthening of telomeres in eukaryotic germ
cells, restoring their original length.
 Telomerase uses a short molecule of RNA as a template to extend the 3’ end of the
 There is now room for primase and DNA polymerase to extend the 5’ end.
 It does not repair the 3’-end “overhang,” but it does lengthen the telomere.
 Telomerase is not present in most cells of multicellular organisms.
 Therefore, the DNA of dividing somatic cells and cultured cells tends to become shorter.
 Telomere length may be a limiting factor in the life span of certain tissues and of the
 Normal shortening of telomeres may protect organisms from cancer by limiting the
number of divisions that somatic cells can undergo.
 Cells from large tumors often have unusually short telomeres, because they have gone
through many cell divisions.
 Active telomerase has been found in some cancerous somatic cells.
 This overcomes the progressive shortening that would eventually lead to self-
destruction of the cancer.
 Immortal strains of cultured cells are capable of unlimited cell division.
 Telomerase may provide a useful target for cancer diagnosis and chemotherapy.

Biology Chapter Notes

Chapter 17 From Gene to Protein
Chapter Notes

Overview: The Flow of Genetic Information

 The information content of DNA is in the form of specific sequences of nucleotides along
the DNA strands.
 The DNA inherited by an organism leads to specific traits by dictating the synthesis of
 Gene expression, the process by which DNA directs protein synthesis, includes two stages
called transcription and translation.
 Proteins are the links between genotype and phenotype.
 For example, Mendel’s dwarf pea plants lack a functioning copy of the gene that
specifies the synthesis of a key protein, gibberellin.
 Gibberellins stimulate the normal elongation of stems.

Concept 17.1 Genes specify proteins via transcription and translation

The study of metabolic defects provided evidence that genes specify proteins.
 In 1909, Archibald Gerrod was the first to suggest that genes dictate phenotype through
enzymes that catalyze specific chemical reactions in the cell.
 He suggested that the symptoms of an inherited disease reflect a person’s inability to
synthesize a particular enzyme.
 He referred to such diseases as “inborn errors of metabolism.”
 Gerrod speculated that alkaptonuria, a hereditary disease, was caused by the absence of an
enzyme that breaks down a specific substrate, alkapton.
 Research conducted several decades later supported Gerrod’s hypothesis.
 Progress in linking genes and enzymes rested on the growing understanding that cells
synthesize and degrade most organic molecules in a series of steps, a metabolic pathway.
 In the 1930s, George Beadle and Boris Ephrussi speculated that each mutation affecting
eye color in Drosophila blocks pigment synthesis at a specific step by preventing
production of the enzyme that catalyzes that step.
 However, neither the chemical reactions nor the enzymes that catalyze them were
known at the time.
 Beadle and Edward Tatum were finally able to establish the link between genes and
enzymes in their exploration of the metabolism of a bread mold, Neurospora crassa.
 They bombarded Neurospora with X-rays and screened the survivors for mutants that
differed in their nutritional needs.
 Wild-type Neurospora can grow on a minimal medium of agar, inorganic salts,
glucose, and the vitamin biotin.
 Beadle and Tatum identified mutants that could not survive on minimal medium, because
they were unable to synthesize certain essential molecules from the minimal ingredients.

Biology Chapter Notes

 However, most of these nutritional mutants can survive on a complete growth medium
that includes all 20 amino acids and a few other nutrients.
 One type of mutant required only the addition of arginine to the minimal growth medium.
 Beadle and Tatum concluded that this mutant was defective somewhere in the
biochemical pathway that normally synthesizes arginine.
 They identified three classes of arginine-deficient mutants, each apparently lacking a
key enzyme at a different step in the synthesis of arginine.
 They demonstrated this by growing these mutant strains in media that provided
different intermediate molecules.
 Their results provided strong evidence for the one gene–one enzyme hypothesis.
 Later research refined the one gene–one enzyme hypothesis.
 First, not all proteins are enzymes.
 Keratin, the structural protein of hair, and insulin, a hormone, both are proteins and
gene products.
 This tweaked the hypothesis to one gene–one protein.
 Later research demonstrated that many proteins are composed of several polypeptides,
each of which has its own gene.
 Therefore, Beadle and Tatum’s idea has been restated as the one gene–one polypeptide
 Some genes code for RNA molecules that play important roles in cells although they are
never translated into protein.
Transcription and translation are the two main processes linking gene to protein.
 Genes provide the instructions for making specific proteins.
 The bridge between DNA and protein synthesis is the nucleic acid RNA.
 RNA is chemically similar to DNA, except that it contains ribose as its sugar and
substitutes the nitrogenous base uracil for thymine.
 An RNA molecule almost always consists of a single strand.
 In DNA or RNA, the four nucleotide monomers act like the letters of the alphabet to
communicate information.
 The specific sequence of hundreds or thousands of nucleotides in each gene carries the
information for the primary structure of proteins, the linear order of the 20 possible amino
 To get from DNA, written in one chemical language, to protein, written in another,
requires two major stages: transcription and translation.
 During transcription, a DNA strand provides a template for the synthesis of a
complementary RNA strand.
 Just as a DNA strand provides a template for the synthesis of each new complementary
strand during DNA replication, it provides a template for assembling a sequence of
RNA nucleotides.
 Transcription of many genes produces a messenger RNA (mRNA) molecule.
 During translation, there is a change of language.
 The site of translation is the ribosome, complex particles that facilitate the orderly
assembly of amino acids into polypeptide chains.

Biology Chapter Notes

 Why can’t proteins be translated directly from DNA?
 The use of an RNA intermediate provides protection for DNA and its genetic
 Using an RNA intermediate allows more copies of a protein to be made
simultaneously, since many RNA transcripts can be made from one gene.
 Also, each gene transcript can be translated repeatedly.
 The basic mechanics of transcription and translation are similar in eukaryotes and
 Because bacteria lack nuclei, their DNA is not segregated from ribosomes and other
protein-synthesizing equipment.
 This allows the coupling of transcription and translation.
 Ribosomes attach to the leading end of an mRNA molecule while transcription is still
in progress.
 In a eukaryotic cell, transcription occurs in the nucleus, and translation occurs at
ribosomes in the cytoplasm.
 The transcription of a protein-coding eukaryotic gene results in pre-mRNA.
 The initial RNA transcript of any gene is called a primary transcript.
 RNA processing yields the finished mRNA.
 To summarize, genes program protein synthesis via genetic messages in the form of
messenger RNA.
 The molecular chain of command in a cell is DNA  RNA  protein.
In the genetic code, nucleotide triplets specify amino acids.
 If the genetic code consisted of a single nucleotide or even pairs of nucleotides per amino
acid, there would not be enough combinations (4 and 16, respectively) to code for all 20
amino acids.
 Triplets of nucleotide bases are the smallest units of uniform length that can code for all
the amino acids.
 With a triplet code, three consecutive bases specify an amino acid, creating 4 3 (64)
possible code words.
 The genetic instructions for a polypeptide chain are written in DNA as a series of
nonoverlapping three-nucleotide words.
 During transcription, one DNA strand, the template strand, provides a template for
ordering the sequence of nucleotides in an RNA transcript.
 A given DNA strand can be the template strand for some genes along a DNA
molecule, while for other genes in other regions, the complementary strand may
function as the template.
 The complementary RNA molecule is synthesized according to base-pairing rules, except
that uracil is the complementary base to adenine.
 Like a new strand of DNA, the RNA molecule is synthesized in an antiparallel direction
to the template strand of DNA.
 The mRNA base triplets are called codons, and they are written in the 5’  3’ direction.
 During translation, the sequence of codons along an mRNA molecule is translated into a
sequence of amino acids making up the polypeptide chain.
 During translation, the codons are read in the 5’  3’ direction along the mRNA.
Biology Chapter Notes
 Each codon specifies which one of the 20 amino acids will be incorporated at the
corresponding position along a polypeptide.
 Because codons are base triplets, the number of nucleotides making up a genetic message
must be three times the number of amino acids making up the protein product.
 It takes at least 300 nucleotides to code for a polypeptide that is 100 amino acids long.
 The task of matching each codon to its amino acid counterpart began in the early 1960s.
 Marshall Nirenberg determined the first match: UUU coded for the amino acid
 He created an artificial mRNA molecule entirely of uracil and added it to a test tube
mixture of amino acids, ribosomes, and other components for protein synthesis.
 This “poly-U” translated into a polypeptide containing a single amino acid,
phenylalanine, in a long chain.
 AAA, GGG, and CCC were solved in the same way.
 Other more elaborate techniques were required to decode mixed triplets such as AUA and
 By the mid-1960s the entire code was deciphered.
 Sixty-one of 64 triplets code for amino acids.
 The codon AUG not only codes for the amino acid methionine, but also indicates the
“start” of translation.
 Three codons do not indicate amino acids but are “stop” signals marking the
termination of translation.
 There is redundancy in the genetic code but no ambiguity.
 Several codons may specify the same amino acid, but no codon specifies more than
one amino acid.
 The redundancy in the code is not random. In many cases, codons that are synonyms
for a particular amino acid differ only in the third base of the triplet.
 To extract the message from the genetic code requires specifying the correct starting
 This establishes the reading frame; subsequent codons are read in groups of three
 The cell’s protein-synthesizing machinery reads the message as a series of
nonoverlapping three-letter words.
 In summary, genetic information is encoded as a sequence of nonoverlapping base
triplets, or codons, each of which is translated into a specific amino acid during protein
The genetic code must have evolved very early in the history of life.
 The genetic code is nearly universal, shared by organisms from the simplest bacteria to
the most complex plants and animals.
 In laboratory experiments, genes can be transcribed and translated after they are
transplanted from one species to another.
 This has permitted bacteria to be programmed to synthesize certain human proteins
after insertion of the appropriate human genes.
 Such applications are exciting developments in biotechnology.
 Exceptions to the universality of the genetic code exist in certain unicellular eukaryotes
and in the organelle genes of some species.
Biology Chapter Notes
 Some prokaryotes can translate stop codons into one of two amino acids not found in
most organisms.
 The evolutionary significance of the near universality of the genetic code is clear.
 A language shared by all living things arose very early in the history of life—early
enough to be present in the common ancestors of all modern organisms.
 A shared genetic vocabulary is a reminder of the kinship that bonds all life on Earth.

Concept 17.2 Transcription is the DNA-directed synthesis of RNA: a closer look

 Messenger RNA, the carrier of information from DNA to the cell’s protein-synthesizing
machinery, is transcribed from the template strand of a gene.
 RNA polymerase separates the DNA strands at the appropriate point and bonds the RNA
nucleotides as they base-pair along the DNA template.
 Like DNA polymerases, RNA polymerases can only assemble a polynucleotide in its
5’  3’ direction.
 Unlike DNA polymerases, RNA polymerases are able to start a chain from scratch;
they don’t need a primer.
 Specific sequences of nucleotides along the DNA mark where gene transcription begins
and ends.
 RNA polymerase attaches and initiates transcription at the promoter.
 In prokaryotes, the sequence that signals the end of transcription is called the
 Molecular biologists refer to the direction of transcription as “downstream” and the other
direction as “upstream.”
 The stretch of DNA that is transcribed into an RNA molecule is called a transcription
 Bacteria have a single type of RNA polymerase that synthesizes all RNA molecules.
 In contrast, eukaryotes have three RNA polymerases (I, II, and III) in their nuclei.
 RNA polymerase II is used for mRNA synthesis.
 Transcription can be separated into three stages: initiation, elongation, and termination of
the RNA chain.
 The presence of a promoter sequence determines which strand of the DNA helix is the
 Within the promoter is the starting point for the transcription of a gene.
 The promoter also includes a binding site for RNA polymerase several dozen
nucleotides “upstream” of the start point.
 In prokaryotes, RNA polymerase can recognize and bind directly to the promoter region.
 In eukaryotes, proteins called transcription factors mediate the binding of RNA
polymerase and the initiation of transcription.
 Only after certain transcription factors are attached to the promoter does RNA polymerase
II bind to it.
 The completed assembly of transcription factors and RNA polymerase II bound to a
promoter is called a transcription initiation complex.
 A crucial promoter DNA sequence is called a TATA box.
Biology Chapter Notes
 RNA polymerase then starts transcription.
 As RNA polymerase moves along the DNA, it untwists the double helix, 10 to 20 bases at
 The enzyme adds nucleotides to the 3’ end of the growing strand.
 Behind the point of RNA synthesis, the double helix re-forms and the RNA molecule
peels away.
 Transcription progresses at a rate of 60 nucleotides per second in eukaryotes.
 A single gene can be transcribed simultaneously by several RNA polymerases at a time.
 A growing strand of RNA trails off from each polymerase.
 The length of each new strand reflects how far along the template the enzyme has
traveled from the start point.
 The congregation of many polymerase molecules simultaneously transcribing a single
gene increases the amount of mRNA transcribed from it.
 This helps the cell make the encoded protein in large amounts.
 Transcription proceeds until after the RNA polymerase transcribes a terminator sequence
in the DNA.
 In prokaryotes, RNA polymerase stops transcription right at the end of the terminator.
 Both the RNA and DNA are then released.
 In eukaryotes, the pre-mRNA is cleaved from the growing RNA chain while RNA
polymerase II continues to transcribe the DNA.
 Specifically, the polymerase transcribes a DNA sequence called the
polyadenylation signal sequence that codes for a polyadenylation sequence
(AAUAAA) in the pre-mRNA.
 At a point about 10 to 35 nucleotides past this sequence, the pre-mRNA is cut from
the enzyme.
 The polymerase continues transcribing for hundreds of nucleotides.
 Transcription is terminated when the polymerase eventually falls off the DNA.

Concept 17.3 Eukaryotic cells modify RNA after transcription

 Enzymes in the eukaryotic nucleus modify pre-mRNA before the genetic messages are
dispatched to the cytoplasm.
 During RNA processing, both ends of the primary transcript are usually altered.
 Certain interior parts of the molecule are cut out and the remaining parts spliced
 At the 5’ end of the pre-mRNA molecule, a modified form of guanine is added, the 5’
 At the 3’ end, an enzyme adds 50 to 250 adenine nucleotides, the poly-A tail.
 These modifications share several important functions.
 They seem to facilitate the export of mRNA from the nucleus.
 They help protect mRNA from hydrolytic enzymes.
 They help the ribosomes attach to the 5’ end of the mRNA.
 The most remarkable stage of RNA processing occurs during the removal of a large
portion of the RNA molecule in a cut-and-paste job of RNA splicing.
Biology Chapter Notes
 Most eukaryotic genes and their RNA transcripts have long noncoding stretches of
 Noncoding segments of nucleotides called intervening regions, or introns, lie between
coding regions.
 The final mRNA transcript includes coding regions, exons, which are translated into
amino acid sequences, plus the leader and trailer sequences.
 RNA splicing removes introns and joins exons to create an mRNA molecule with a
continuous coding sequence.
 This splicing is accomplished by a spliceosome.
 Spliceosomes consist of a variety of proteins and several small nuclear
ribonucleoproteins (snRNPs) that recognize the splice sites.
 snRNPs are located in the cell nucleus and are composed of RNA and protein
 Each snRNP has several protein molecules and a small nuclear RNA molecule
 Each snRNA is about 150 nucleotides long.
 The spliceosome interacts with certain sites along an intron, releasing the introns and
joining together the two exons that flanked the introns.
 snRNAs appear to play a major role in catalytic processes, as well as spliceosome
assembly and splice site recognition.
 The idea of a catalytic role for snRNA arose from the discovery of ribozymes, RNA
molecules that function as enzymes.
 In some organisms, splicing occurs without proteins or additional RNA molecules.
 The intron RNA functions as a ribozyme and catalyzes its own excision.
 For example, in the protozoan Tetrahymena, self-splicing occurs in the production of
ribosomal RNA (rRNA), a component of the organism’s ribosomes.
 The pre-rRNA actually removes its own introns.
 The discovery of ribozymes rendered obsolete the statement, “All biological catalysts are
 The fact that RNA is single-stranded plays an important role in allowing certain RNA
molecules to function as ribozymes.
 A region of the RNA molecule may base-pair with a complementary region elsewhere in
the same molecule, thus giving the RNA a specific 3-D structure that is key to its ability
to catalyze reactions.
 Introns and RNA splicing appear to have several functions.
 Some introns play a regulatory role in the cell. These introns contain sequences that
control gene activity in some way.
 Splicing itself may regulate the passage of mRNA from the nucleus to the cytoplasm.
 One clear benefit of split genes is to enable one gene to encode for more than one
 Alternative RNA splicing gives rise to two or more different polypeptides, depending on
which segments are treated as exons.
 Sex differences in fruit flies may be due to differences in splicing RNA transcribed
from certain genes.
 Early results of the Human Genome Project indicate that this phenomenon may be
common in humans, and may explain why we have a relatively small number of genes.
Biology Chapter Notes
 Proteins often have a modular architecture with discrete structural and functional regions
called domains.
 The presence of introns in a gene may facilitate the evolution of new and potentially
useful proteins as a result of a process known as exon shuffling.
 In many cases, different exons code for different domains of a protein.
 The presence of introns increases the probability of potentially beneficial crossing over
between genes.
 Introns increase the opportunity for recombination between two alleles of a gene.
 This raises the probability that a crossover will switch one version of an exon for
another version found on the homologous chromosome.
 There may also be occasional mixing and matching of exons between completely
different genes.
 Either way, exon shuffling can lead to new proteins through novel combinations of

Concept 17.4 Translation is the RNA-directed synthesis of a polypeptide: a closer look

 In the process of translation, a cell interprets a series of codons along an mRNA molecule
and builds a polypeptide.
 The interpreter is transfer RNA (tRNA), which transfers amino acids from the
cytoplasmic pool to a ribosome.
 A cell has all 20 amino acids available in its cytoplasm, either by synthesizing them
from scratch or by taking them up from the surrounding solution.
 The ribosome adds each amino acid carried by tRNA to the growing end of the
polypeptide chain.
 During translation, each type of tRNA links an mRNA codon with the appropriate amino
 Each tRNA arriving at the ribosome carries a specific amino acid at one end and has a
specific nucleotide triplet, an anticodon, at the other.
 The anticodon base-pairs with a complementary codon on mRNA.
 If the codon on mRNA is UUU, a tRNA with an AAA anticodon and carrying
phenylalanine will bind to it.
 Codon by codon, tRNAs deposit amino acids in the prescribed order, and the ribosome
joins them into a polypeptide chain.
 The tRNA molecule is a translator, because it can read a nucleic acid word (the mRNA
codon) and translate it to a protein word (the amino acid).
 Like other types of RNA, tRNA molecules are transcribed from DNA templates in the
 Once it reaches the cytoplasm, each tRNA is used repeatedly, picking up its designated
amino acid in the cytosol, depositing the amino acid at the ribosome, and returning to the
cytosol to pick up another copy of that amino acid.
 A tRNA molecule consists of a strand of about 80 nucleotides that folds back on itself to
form a three-dimensional structure.
 It includes a loop containing the anticodon and an attachment site at the 3’ end for an
amino acid.
Biology Chapter Notes
 If each anticodon had to be a perfect match to each codon, we would expect to find 61
types of tRNA, but the actual number is about 45.
 The anticodons of some tRNAs recognize more than one codon.
 This is possible because the rules for base pairing between the third base of the codon and
anticodon are relaxed (called wobble).
 At the wobble position, U on the anticodon can bind with A or G in the third position
of a codon.
 Wobble explains why the synonymous codons for a given amino acid can differ in
their third base, but not usually in their other bases.
 Each amino acid is joined to the correct tRNA by aminoacyl-tRNA synthetase.
 The 20 different synthetases match the 20 different amino acids.
 Each has active sites for only a specific tRNA-and-amino-acid combination.
 The synthetase catalyzes a covalent bond between them in a process driven by ATP
 The result is an aminoacyl-tRNA or activated amino acid.
 Ribosomes facilitate the specific coupling of the tRNA anticodons with mRNA codons
during protein synthesis.
 Each ribosome is made up of a large and a small subunit.
 The subunits are composed of proteins and ribosomal RNA (rRNA), the most
abundant RNA in the cell.
 In eukaryotes, the subunits are made in the nucleolus.
 After rRNA genes are transcribed to rRNA in the nucleus, the rRNA and proteins are
assembled to form the subunits with proteins from the cytoplasm.
 The subunits exit the nucleus via nuclear pores.
 The large and small subunits join to form a functional ribosome only when they attach to
an mRNA molecule.
 While very similar in structure and function, prokaryotic and eukaryotic ribosomes have
enough differences that certain antibiotic drugs (like tetracycline) can paralyze
prokaryotic ribosomes without inhibiting eukaryotic ribosomes.
 Each ribosome has a binding site for mRNA and three binding sites for tRNA molecules.
 The P site holds the tRNA carrying the growing polypeptide chain.
 The A site carries the tRNA with the next amino acid to be added to the chain.
 Discharged tRNAs leave the ribosome at the E (exit) site.
 The ribosome holds the tRNA and mRNA in close proximity and positions the new amino
acid for addition to the carboxyl end of the growing polypeptide.
 It then catalyzes the formation of the peptide bond.
 As the polypeptide becomes longer, it passes through an exit tunnel in the ribosome’s
large unit and is released to the cytosol.
 Recent advances in our understanding of the structure of the ribosome strongly support
the hypothesis that rRNA, not protein, carries out the ribosome’s functions.
 RNA is the main constituent at the interphase between the two subunits and of the A
and P sites.
 It is the catalyst for peptide bond formation.
 A ribosome can be regarded as one colossal ribozyme.
Biology Chapter Notes
 Translation can be divided into three stages: initiation, elongation, and termination.
 All three phases require protein “factors” that aid in the translation process.
 Both initiation and chain elongation require energy provided by the hydrolysis of GTP.
 Initiation brings together mRNA, a tRNA with the first amino acid, and the two
ribosomal subunits.
 First, a small ribosomal subunit binds with mRNA and a special initiator tRNA, which
carries methionine and attaches to the start codon.
 The small subunit then moves downstream along the mRNA until it reaches the start
codon, AUG, which signals the start of translation.
 This establishes the reading frame for the mRNA.
 The initiator tRNA, already associated with the complex, then hydrogen-bonds with
the start codon.
 Proteins called initiation factors bring in the large subunit so that the initiator tRNA
occupies the P site.
 Elongation involves the participation of several protein elongation factors, and consists of
a series of three-step cycles as each amino acid is added to the proceeding one.
 During codon recognition, an elongation factor assists hydrogen bonding between the
mRNA codon under the A site with the corresponding anticodon of tRNA carrying the
appropriate amino acid.
 This step requires the hydrolysis of two GTP.
 During peptide bond formation, an rRNA molecule catalyzes the formation of a
peptide bond between the polypeptide in the P site with the new amino acid in the A
 This step separates the tRNA at the P site from the growing polypeptide chain and
transfers the chain, now one amino acid longer, to the tRNA at the A site.
 During translocation, the ribosome moves the tRNA with the attached polypeptide
from the A site to the P site.
 Because the anticodon remains bonded to the mRNA codon, the mRNA moves
along with it.
 The next codon is now available at the A site.
 The tRNA that had been in the P site is moved to the E site and then leaves the
 Translocation is fueled by the hydrolysis of GTP.
 Effectively, translocation ensures that the mRNA is “read” 5’  3’ codon by
 • The three steps of elongation continue to add amino acids codon by codon until
the polypeptide chain is completed.
 Termination occurs when one of the three stop codons reaches the A site.
 A release factor binds to the stop codon and hydrolyzes the bond between the
polypeptide and its tRNA in the P site.
 This frees the polypeptide, and the translation complex disassembles.
 Typically a single mRNA is used to make many copies of a polypeptide simultaneously.
 Multiple ribosomes, polyribosomes, may trail along the same mRNA.
 Polyribosomes can be found in prokaryotic and eukaryotic cells.
 A ribosome requires less than a minute to translate an average-sized mRNA into a
Biology Chapter Notes
 During and after synthesis, a polypeptide coils and folds to its three-dimensional shape
 The primary structure, the order of amino acids, determines the secondary and tertiary
 Chaperone proteins may aid correct folding.
 In addition, proteins may require posttranslational modifications before doing their
particular job.
 This may require additions such as sugars, lipids, or phosphate groups to amino acids.
 Enzymes may remove some amino acids or cleave whole polypeptide chains.
 Two or more polypeptides may join to form a protein.
Signal peptides target some eukaryotic polypeptides to specific destinations in the cell.
 Two populations of ribosomes, free and bound, are active participants in protein synthesis.
 Free ribosomes are suspended in the cytosol and synthesize proteins that reside in the
 Bound ribosomes are attached to the cytosolic side of the endoplasmic reticulum.
 They synthesize proteins of the endomembrane system as well as proteins secreted
from the cell.
 While bound and free ribosomes are identical in structure, their location depends on the
type of protein that they are synthesizing.
 Translation in all ribosomes begins in the cytosol, but a polypeptide destined for the
endomembrane system or for export has a specific signal peptide region at or near the
leading end.
 This consists of a sequence of about 20 amino acids.
 A signal recognition particle (SRP) binds to the signal peptide and attaches it and its
ribosome to a receptor protein in the ER membrane.
 The SRP consists of a protein-RNA complex.
 After binding, the SRP leaves and protein synthesis resumes with the growing polypeptide
snaking across the membrane into the cisternal space via a protein pore.
 An enzyme usually cleaves the signal polypeptide.
 Secretory proteins are released entirely into the cisternal space, but membrane proteins
remain partially embedded in the ER membrane.
 Other kinds of signal peptides are used to target polypeptides to mitochondria,
chloroplasts, the nucleus, and other organelles that are not part of the endomembrane
 In these cases, translation is completed in the cytosol before the polypeptide is
imported into the organelle.
 While the mechanisms of translocation vary, each of these polypeptides has a “ZIP
code” that ensures its delivery to the correct cellular location.
 Prokaryotes also employ signal sequences to target proteins for secretion.

Concept 17.5 RNA plays multiple roles in the cell: a review

 The cellular machinery of protein synthesis and ER targeting is dominated by various
kinds of RNA.
Biology Chapter Notes
 In addition to mRNA, these include tRNA; rRNA; and in eukaryotes, snRNA and SRP
 A type of RNA called small nucleolar RNA (snoRNA) aids in processing pre-rRNA
transcripts in the nucleolus, a process necessary for ribosome formation.
 Recent research has also revealed the presence of small, single-stranded and double-
stranded RNA molecules that play important roles in regulating which genes get
 These types of RNA include small interfering RNA (siRNA) and microRNA
 The diverse functions of RNA are based, in part, on its ability to form hydrogen bonds
with other nucleic acid molecules (DNA or RNA).
 It can also assume a specific three-dimensional shape by forming hydrogen bonds
between bases in different parts of its polynucleotide chain.
 DNA may be the genetic material of all living cells today, but RNA is much more
 The diverse functions of RNA range from structural to informational to catalytic.

Concept 17.6 Comparing gene expression in prokaryotes and eukaryotes reveals key
 Although prokaryotes and eukaryotes carry out transcription and translation in very
similar ways, they do have differences in cellular machinery and in details of the
 Eukaryotic RNA polymerases differ from those of prokaryotes and require
transcription factors.
 They differ in how transcription is terminated.
 Their ribosomes also are different.
 One major difference is that prokaryotes can transcribe and translate the same gene
 The new protein quickly diffuses to its operating site.
 In eukaryotes, the nuclear envelope segregates transcription from translation.
 In addition, extensive RNA processing is carried out between these processes.
 This provides additional steps whose regulation helps coordinate the elaborate
activities of a eukaryotic cell.
 Eukaryotic cells also have complicated mechanisms for targeting proteins to the
appropriate organelle.

Concept 17.7 Point mutations can affect protein structure and function
 Mutations are changes in the genetic material of a cell (or virus).
 These include large-scale mutations in which long segments of DNA are affected (for
example, translocations, duplications, and inversions).
 A chemical change in just one base pair of a gene causes a point mutation.
 If these occur in gametes or cells producing gametes, they may be transmitted to future

Biology Chapter Notes

 For example, sickle-cell disease is caused by a mutation of a single base pair in the gene
that codes for one of the polypeptides of hemoglobin.
 A change in a single nucleotide from T to A in the DNA template leads to an abnormal
 A point mutation that results in the replacement of a pair of complementary nucleotides
with another nucleotide pair is called a base-pair substitution.
 Some base-pair substitutions have little or no impact on protein function.
 In silent mutations, altered nucleotides still code for the same amino acids because of
redundancy in the genetic code.
 Other changes lead to switches from one amino acid to another with similar properties.
 Still other mutations may occur in a region where the exact amino acid sequence is not
essential for function.
 Other base-pair substitutions cause a readily detectable change in a protein.
 These are usually detrimental but can occasionally lead to an improved protein or one
with novel capabilities.
 Changes in amino acids at crucial sites, especially active sites, are likely to impact
 Missense mutations are those that still code for an amino acid but a different one.
 Nonsense mutations change an amino acid codon into a stop codon, nearly always
leading to a nonfunctional protein.
 Insertions and deletions are additions or losses of nucleotide pairs in a gene.
 These have a disastrous effect on the resulting protein more often than substitutions do.
 Unless insertion or deletion mutations occur in multiples of three, they cause a frameshift
 All the nucleotides downstream of the deletion or insertion will be improperly grouped
into codons.
 The result will be extensive missense, ending sooner or later in nonsense—premature
 Mutations can occur in a number of ways.
 Errors can occur during DNA replication, DNA repair, or DNA recombination.
 These can lead to base-pair substitutions, insertions, or deletions, as well as mutations
affecting longer stretches of DNA.
 These are called spontaneous mutations.
 Rough estimates suggest that about 1 nucleotide in every 10 10 is altered and inherited by
daughter cells.
 Mutagens are chemical or physical agents that interact with DNA to cause mutations.
 Physical agents include high-energy radiation like X-rays and ultraviolet light.
 Chemical mutagens fall into several categories.
 Some chemicals are base analogues that may be substituted into DNA, but they pair
incorrectly during DNA replication.
 Other mutagens interfere with DNA replication by inserting into DNA and distorting
the double helix.
 Still others cause chemical changes in bases that change their pairing properties.

Biology Chapter Notes

 Researchers have developed various methods to test the mutagenic activity of different
 These tests are often used as a preliminary screen of chemicals to identify those that
may cause cancer.
 This makes sense because most carcinogens are mutagenic and most mutagens are
What is a gene? We revisit the question.
 The Mendelian concept of a gene views it as a discrete unit of inheritance that affects
 Morgan and his colleagues assigned genes to specific loci on chromosomes.
 We can also view a gene as a specific nucleotide sequence along a region of a DNA
 We can define a gene functionally as a DNA sequence that codes for a specific
polypeptide chain.
 All these definitions are useful in certain contexts.
 Even the one gene–one polypeptide definition must be refined and applied selectively.
 Most eukaryotic genes contain large introns that have no corresponding segments in
 Promoters and other regulatory regions of DNA are not transcribed either, but they
must be present for transcription to occur.
 Our molecular definition must also include the various types of RNA that are not
translated into polypeptides, such as rRNA, tRNA, and other RNAs.
 This is our definition of a gene: A gene is a region of DNA whose final product is either a
polypeptide or an RNA molecule.

Biology Chapter Notes

Chapter 18 The Genetics of Viruses and Bacteria
Chapter Notes

Overview: Microbial Model Systems

 Viruses and bacteria are the simplest biological systems—microbial models in which
scientists find life’s fundamental molecular mechanisms in their most basic, accessible
 Molecular biology was born in the laboratories of microbiologists studying viruses and
 Microbes such as E. coli and its viruses are called model systems because of their use
in studies that reveal broad biological principles.
 Microbiologists provided most of the evidence that genes are made of DNA, and they
worked out most of the major steps in DNA replication, transcription, and translation.
 Techniques enabling scientists to manipulate genes and transfer them from one
organism to another were developed in microbes.
 In addition, viruses and bacteria have unique genetic features with implications for
understanding the diseases that they cause.
 Bacteria are prokaryotic organisms, with cells that are much smaller and more simply
organized than those of eukaryotes, such as plants and animals.
 Viruses are smaller and simpler still, lacking the structure and metabolic machinery of
 Most viruses are little more than aggregates of nucleic acids and protein—genes in a
protein coat.

Concept 18.1 A virus has a genome but can reproduce only within a host cell
Researchers discovered viruses by studying a plant disease.
 The story of how viruses were discovered begins in 1883 with research on the cause of
tobacco mosaic disease by Adolf Mayer.
 This disease stunts tobacco plant growth and mottles plant leaves.
 Mayer concluded that the disease was infectious when he found that he could transmit
the disease by rubbing sap from diseased leaves onto healthy plants.
 He concluded that the disease must be caused by an extremely small bacterium.
 Ten years later, Dimitri Ivanovsky demonstrated that the sap was still infectious even
after passing through a filter designed to remove bacteria.
 In 1897, Martinus Beijerinck ruled out the possibility that the disease was due to a
filterable toxin produced by a bacterium by demonstrating that the infectious agent could
 The sap from one generation of infected plants could be used to infect a second
generation of plants that could infect subsequent generations.
 Beijerinck also determined that the pathogen could reproduce only within the host,
could not be cultivated on nutrient media, and was not inactivated by alcohol,
generally lethal to bacteria.
Biology Chapter Notes
 In 1935, Wendell Stanley crystallized the pathogen, the tobacco mosaic virus (TMV).
A virus is a genome enclosed in a protective coat.
 Stanley’s discovery that some viruses could be crystallized was puzzling because not even
the simplest cells can aggregate into regular crystals.
 However, viruses are not cells.
 They are infectious particles consisting of nucleic acid encased in a protein coat and, in
some cases, a membranous envelope.
 The tiniest viruses are only 20 nm in diameter—smaller than a ribosome.
 The genome of viruses may consist of double-stranded DNA, single-stranded DNA,
double-stranded RNA, or single-stranded RNA, depending on the kind of virus.
 A virus is called a DNA virus or an RNA virus, according to the kind of nucleic acid
that makes up its genome.
 The viral genome is usually organized as a single linear or circular molecule of nucleic
 The smallest viruses have only four genes, while the largest have several hundred.
 The capsid is the protein shell enclosing the viral genome.
 Capsids are built of a large number of protein subunits called capsomeres.
 The number of different kinds of proteins making up the capsid is usually small.
 The capsid of the tobacco mosaic virus has more than 1,000 copies of the same protein.
 Adenoviruses have 252 identical proteins arranged into a polyhedral capsid—as an
 Some viruses have accessory structures to help them infect their hosts.
 A membranous envelope surrounds the capsids of flu viruses.
 These viral envelopes are derived from the membrane of the host cell.
 They also have some host cell viral proteins and glycoproteins, as well as molecules of
viral origin.
 Some viruses carry a few viral enzyme molecules within their capsids.
 The most complex capsids are found in viruses that infect bacteria, called bacteriophages
or phages.
 The T-even phages (T2, T4, T6) that infect Escherichia coli have elongated icosahedral
capsid heads that enclose their DNA and a protein tailpiece that attaches the phage to the
host and injects the phage DNA inside.
Viruses can reproduce only within a host cell.
 Viruses are obligate intracellular parasites.
 They can reproduce only within a host cell.
 An isolated virus is unable to reproduce—or do anything else, except infect an appropriate
 Viruses lack the enzymes for metabolism and the ribosomes for protein synthesis.
 An isolated virus is merely a packaged set of genes in transit from one host cell to
 Each type of virus can infect and parasitize only a limited range of host cells, called its
host range.
Biology Chapter Notes
 This host specificity depends on the evolution of recognition systems by the virus.
 Viruses identify host cells by a “lock and key” fit between proteins on the outside of
the virus and specific receptor molecules on the host’s surface (which evolved for
functions that benefit the host).
 Some viruses have a broad enough host range to infect several species, while others infect
only a single species.
 West Nile virus can infect mosquitoes, birds, horses, and humans.
 Measles virus can infect only humans.
 Most viruses of eukaryotes attack specific tissues.
 Human cold viruses infect only the cells lining the upper respiratory tract.
 The AIDS virus binds only to certain white blood cells.
 A viral infection begins when the genome of the virus enters the host cell.
 Once inside, the viral genome commandeers its host, reprogramming the cell to copy viral
nucleic acid and manufacture proteins from the viral genome.
 The host provides nucleotides, ribosomes, tRNAs, amino acids, ATP, and other
components for making the viral components dictated by viral genes.
 Most DNA viruses use the DNA polymerases of the host cell to synthesize new genomes
along the templates provided by the viral DNA.
 RNA viruses use special virus-encoded polymerases that can use RNA as a template.
 The nucleic acid molecules and capsomeres then self-assemble into viral particles and exit
the cell.
 Tobacco mosaic virus RNA and capsomeres can be assembled to form complete
viruses if the components are mixed together under the right conditions.
 The simplest type of viral reproductive cycle ends with the exit of many viruses from the
infected host cell, a process that usually damages or destroys the host cell.
Phages reproduce using lytic or lysogenic cycles.
 While phages are the best understood of all viruses, some of them are also among the
most complex.
 Research on phages led to the discovery that some double-stranded DNA viruses can
reproduce by two alternative mechanisms: the lytic cycle and the lysogenic cycle.
 In the lytic cycle, the phage reproductive cycle culminates in the death of the host.
 In the last stage, the bacterium lyses (breaks open) and releases the phages produced
within the cell to infect others.
 Each of these phages can infect a healthy cell.
 Virulent phages reproduce only by a lytic cycle.
 While phages have the potential to wipe out a bacterial colony in just hours, bacteria have
defenses against phages.
 Natural selection favors bacterial mutants with receptor sites that are no longer
recognized by a particular type of phage.
 Bacteria produce restriction endonucleases, or restriction enzymes, that recognize and
cut up foreign DNA, including certain phage DNA.
 Chemical modifications to the bacteria’s own DNA prevent its destruction by
restriction nucleases.
 Natural selection also favors phage mutants that are resistant to restriction enzymes.
Biology Chapter Notes
 In the lysogenic cycle, the phage genome replicates without destroying the host cell.
 Temperate phages, like phage lambda, use both lytic and lysogenic cycles.
 The lambda phage that infects E. coli demonstrates the cycles of a temperate phage.
 Infection of an E. coli by phage lambda begins when the phage binds to the surface of the
cell and injects its DNA.
 What happens next depends on the reproductive mode: lytic or lysogenic cycle.
 During a lytic cycle, the viral genes turn the host cell into a lambda phage-producing
factory, and the cell lyses and releases its viral products.
 During a lysogenic cycle, the viral DNA molecule is incorporated by genetic
recombination into a specific site on the host cell’s chromosome.
 In this prophage stage, one of the viral genes codes for a protein that represses most other
prophage genes.
 As a result, the phage genome is largely silent.
 A few other prophage genes may also be expressed during lysogenic cycles.
 Expression of these genes may alter the host’s phenotype, which can have medical
 Every time the host divides, it copies the phage DNA and passes the copies to daughter
 The viruses propagate without killing the host cells on which they depend.
 The term lysogenic implies that prophages are capable of giving rise to active phages that
lyse their host cells.
 That happens when the viral genome exits the bacterial chromosome and initiates a lytic
Animal viruses are diverse in their modes of infection and replication.
 Many variations on the basic scheme of viral infection and reproduction are represented
among animal viruses.
 One key variable is the type of nucleic acid that serves as a virus’s genetic material.
 Another variable is the presence or absence of a membranous envelope derived from
the host cell membrane.
 Most animal viruses with RNA genomes have an envelope, as do some with DNA
 Viruses equipped with an outer envelope use the envelope to enter the host cell.
 Glycoproteins on the envelope bind to specific receptors on the host’s membrane.
 The envelope fuses with the host’s membrane, transporting the capsid and viral
genome inside.
 The viral genome duplicates and directs the host’s protein synthesis machinery to
synthesize capsomeres with free ribosomes and glycoproteins with bound ribosomes.
 After the capsid and viral genome self-assemble, they bud from the host cell covered
with an envelope derived from the host’s plasma membrane, including viral
 The viral envelope is thus derived from the host’s plasma membrane, although viral genes
specify some of the molecules in the membrane.
 These enveloped viruses do not necessarily kill the host cell.
 Some viruses have envelopes that are not derived from plasma membrane.
Biology Chapter Notes
 The envelope of the herpesvirus is derived from the nuclear envelope of the host.
 These double-stranded DNA viruses reproduce within the cell nucleus using viral and
cellular enzymes to replicate and transcribe their DNA.
 In some cases, copies of the herpesvirus DNA remain behind as minichromosomes in
the nuclei of certain nerve cells.
 There they remain for life until triggered by physical or emotional stress to leave the
genome and initiate active viral production.
 The infection of other cells by these new viruses causes cold or genital sores.
 The viruses that use RNA as the genetic material are quite diverse, especially those that
infect animals.
 In some with single-stranded RNA (class IV), the genome acts as mRNA and is
translated directly.
 In others (class V), the RNA genome serves as a template for complementary RNA
strands, which function both as mRNA and as templates for the synthesis of additional
copies of genome RNA.
 All viruses that require RNA  RNA synthesis to make mRNA use a viral enzyme
that is packaged with the genome inside the capsid.
 Retroviruses (class VI) have the most complicated life cycles.
 These carry an enzyme called reverse transcriptase that transcribes DNA from an
RNA template.
 This provides RNA  DNA information flow.
 The newly made DNA is inserted as a provirus into a chromosome in the animal cell.
 The host’s RNA polymerase transcribes the viral DNA into more RNA molecules.
 These can function both as mRNA for the synthesis of viral proteins and as
genomes for new virus particles released from the cell.
 Human immunodeficiency virus (HIV), the virus that causes AIDS (acquired
immunodeficiency syndrome) is a retrovirus.
 The reproductive cycle of HIV illustrates the pattern of infection and replication in a
 The viral particle includes an envelope with glycoproteins for binding to specific types of
red blood cells, a capsid containing two identical RNA strands as its genome, and two
copies of reverse transcriptase.
 After HIV enters the host cell, reverse transcriptase molecules are released into the
cytoplasm and catalyze synthesis of viral DNA.
 The host’s polymerase transcribes the proviral DNA into RNA molecules that can
function both as mRNA for the synthesis of viral proteins and as genomes for new virus
particles released from the cell.
 Transcription produces more copies of the viral RNA that are translated into viral
proteins, which self-assemble into a virus particle and leave the host.
Viruses may have evolved from other mobile genetic elements.
 Viruses do not fit our definition of living organisms.
 An isolated virus is biologically inert, and yet it has a genetic program written in the
universal language of life.
 Although viruses are obligate intracellular parasites that cannot reproduce independently,
it is hard to deny their evolutionary connection to the living world.
Biology Chapter Notes
 Because viruses depend on cells for their own propagation, it is reasonable to assume that
they evolved after the first cells appeared.
 Most molecular biologists favor the hypothesis that viruses originated from fragments of
cellular nucleic acids that could move from one cell to another.
 A viral genome usually has more in common with the genome of its host than with
those of viruses infecting other hosts.
 However, some viruses have genetic sequences that are quite similar to seemingly
distantly related viruses.
 This genetic similarity may reflect the persistence of groups of viral genes that were
evolutionarily successful during the early evolution of viruses and their eukaryotic
host cells.
 Perhaps the earliest viruses were naked bits of nucleic acids that passed between cells via
injured cell surfaces.
 The evolution of capsid genes may have facilitated the infection of undamaged cells.
 Candidates for the original sources of viral genomes include plasmids and transposable
 Plasmids are small, circular DNA molecules that are separate from chromosomes.
 Plasmids, found in bacteria and in eukaryote yeast, can replicate independently of the
rest of the cell and are occasionally transferred between cells.
 Transposable elements are DNA segments that can move from one location to another
within a cell’s genome.
 Both plasmids and transposable elements are mobile genetic elements.
 The ongoing evolutionary relationship between viruses and the genomes of their hosts is
an association that makes viruses very useful model systems in molecular biology.

Concept 18.2 Viruses, viroids, and prions are formidable pathogens in animals and
 The link between viral infection and the symptoms it produces is often obscure.
 Some viruses damage or kill cells by triggering the release of hydrolytic enzymes from
 Some viruses cause the infected cell to produce toxins that lead to disease symptoms.
 Others have molecular components, such as envelope proteins, that are toxic.
 In some cases, viral damage is easily repaired (respiratory epithelium after a cold), but in
others, infection causes permanent damage (nerve cells after polio).
 Many of the temporary symptoms associated with a viral infection result from the body’s
own efforts at defending itself against infection.
 The immune system is a complex and critical part of the body’s natural defense
mechanism against viral and other infections.
 Modern medicine has developed vaccines, harmless variants or derivatives of pathogenic
microbes that stimulate the immune system to mount defenses against the actual pathogen.
 Vaccination has eradicated smallpox.
 Effective vaccines are available against polio, measles, rubella, mumps, hepatitis B,
and a number of other viral diseases.
 Medical technology can do little to cure viral diseases once they occur.
Biology Chapter Notes
 Antibiotics, which can kill bacteria by inhibiting enzymes or processes specific to
bacteria, are powerless against viruses, which have few or no enzymes of their own.
 Most antiviral drugs resemble nucleosides and interfere with viral nucleic acid
 An example is acyclovir, which impedes herpesvirus reproduction by inhibiting the
viral polymerase that synthesizes viral DNA.
 Azidothymidine (AZT) curbs HIV reproduction by interfering with DNA synthesis by
reverse transcriptase.
 Currently, multidrug “cocktails” are the most effective treatment for HIV.
New viral diseases are emerging.
 In recent years, several emerging viruses have risen to prominence.
 HIV, the AIDS virus, seemed to appear suddenly in the early 1980s.
 Each year new strains of influenza virus cause millions to miss work or class, and
deaths are not uncommon.
 The deadly Ebola virus has caused hemorrhagic fevers in central Africa periodically
since 1976.
 West Nile virus appeared for the first time in North America in 1999.
 A more recent viral disease is severe acute respiratory syndrome (SARS).
 Researchers identified the disease agent causing SARS as a coronavirus, a class IV
virus with a single-stranded RNA genome.
 The emergence of these new viral diseases is due to three processes: mutation; spread of
existing viruses from one species to another; and dissemination of a viral disease from a
small, isolated population.
 Mutation of existing viruses is a major source of new viral diseases.
 RNA viruses tend to have high mutation rates because replication of their nucleic acid
lacks proofreading.
 Some mutations create new viral strains with sufficient genetic differences from earlier
strains that they can infect individuals who had acquired immunity to these earlier
 This is the case in flu epidemics.
 Another source of new viral diseases is the spread of existing viruses from one host
species to another.
 It is estimated that about three-quarters of new human diseases originated in other
 For example, hantavirus, which killed dozens of people in 1993, normally infects
rodents, especially deer mice.
 In 1993, unusually wet weather in the southwestern United States increased the mice’s
food, exploding the population.
 Humans acquired hantavirus when they inhaled dust-containing traces of urine and
feces from infected mice.
 The source of the SARS-causing virus is still undetermined, but candidates include the
exotic animal markets in China.
 In early 2004, the first cases of a new bird flu were reported in southeast Asia.
 If this disease evolves to spread from person to person, the potential for a major
human outbreak is great.

Biology Chapter Notes

 Finally, a viral disease can spread from a small, isolated population to a widespread
 For example, AIDS went unnamed and virtually unnoticed for decades before
spreading around the world.
 Technological and social factors, including affordable international travel, blood
transfusion technology, sexual promiscuity, and the abuse of intravenous drugs
allowed a previously rare disease to become a global scourge.
 These emerging viruses are generally not new. Rather, they are existing viruses that
mutate, spread to new host species, or expand their host territory.
 Changes in host behavior and environmental changes can increase the viral traffic
responsible for emerging disease.
 Destruction of forests to expand cropland may bring humans into contact with other
animals that may host viruses that can infect humans.
Plant viruses are serious agricultural pests.
 More than 2,000 types of viral diseases of plants are known.
 These diseases account for an annual loss of $15 billion worldwide.
 Plant viruses can stunt plant growth and diminish crop yields.
 Most are RNA viruses with rod-shaped or polyhedral capsids.
 Plant viral diseases are spread by two major routes.
 In horizontal transmission, a plant is infected with the virus by an external source.
 Plants are more susceptible if their protective epidermis is damaged, perhaps by wind,
chilling, injury, or insects.
 Insects are often carriers of viruses, transmitting disease from plant to plant.
 In vertical transmission, a plant inherits a viral infection from a parent.
 This may occur by asexual propagation or in sexual reproduction via infected seeds.
 Once a virus starts reproducing inside a plant cell, viral particles can spread throughout
the plant by passing through plasmodesmata.
 These cytoplasmic connections penetrate the walls between adjacent cells.
 Proteins encoded by viral genes can alter the diameter of plasmodesmata to allow
passage of viral proteins or genomes.
 Agricultural scientists have focused their efforts largely on reducing the incidence and
transmission of viral disease and in breeding resistant plant varieties.
Viroids and prions are the simplest infectious agents.
 Viroids, smaller and simpler than even viruses, consist of tiny molecules of naked circular
RNA that infect plants.
 Their several hundred nucleotides do not encode for proteins but can be replicated by the
host’s cellular enzymes.
 These small RNA molecules can disrupt plant metabolism and stunt plant growth, perhaps
by causing errors in the regulatory systems that control plant growth.
 Viroids show that molecules can act as infectious agents to spread disease.
 Prions are infectious proteins that spread disease.
 They appear to cause several degenerative brain diseases including scrapie in sheep,
“mad cow disease,” and Creutzfeldt-Jakob disease in humans.
Biology Chapter Notes
 Prions are likely transmitted in food.
 They have two alarming characteristics.
 They are very slow-acting agents. The incubation period is around ten years.
 Prions are virtually indestructible. They are not destroyed or deactivated by heating to
normal cooking temperatures.
 How can a nonreplicating protein be a transmissible pathogen?
 According to the leading hypothesis, a prion is a misfolded form of a normal brain
 When the prion gets into a cell with the normal form of the protein, the prion can convert
the normal protein into the prion version, creating a chain reaction that increases their

Concept 18.3 Rapid reproduction, mutation, and genetic recombination contribute to

the genetic diversity of bacteria
 Bacteria are very valuable as microbial models in genetics research.
 As prokaryotes, bacteria allow researchers to study molecular genetics in simple
 With the advent of large-scale genome sequencing, information about many
prokaryotes has accumulated.
 The best-studied bacterium is Escherichia coli, “the laboratory rat of molecular
 The major component of the bacterial genome is one double-stranded, circular DNA
molecule that is associated with a small amount of protein.
 For E. coli, the chromosomal DNA consists of about 4.6 million nucleotide pairs with
about 4,400 genes.
 This is 100 times more DNA than in a typical virus and 1,000 times less than in a
typical eukaryote cell.
 Tight coiling of DNA results in a dense region of DNA, called the nucleoid, which is
not bound by a membrane.
 In addition, many bacteria have plasmids, much smaller circles of DNA.
 Each plasmid has only a small number of genes, from just a few to several dozen.
 Bacterial cells divide by binary fission.
 This is preceded by replication of the bacterial chromosome from a single origin of
 Bacteria proliferate very rapidly in a favorable natural or laboratory environment.
 Under optimal laboratory conditions, E. coli can divide every 20 minutes, producing a
colony of 107 to 108 bacteria in as little as 12 hours.
 In the human colon, E. coli grows more slowly and can double every 12 hours.
 It does reproduce rapidly enough to replace the 2 × 10 10 bacteria lost each day in feces.
 Through binary fission, most of the bacteria in a colony are genetically identical to the
parent cell.
 However, the spontaneous mutation rate of E. coli is 1 × 10−7 mutations per gene per
cell division.

Biology Chapter Notes

 This produces about 2,000 bacteria per day in the human colon that have a mutation in
any one gene.
 About 9 million mutant E. coli are produced in the human gut each day.
 New mutations, though individually rare, can have a significant impact on genetic
diversity when reproductive rates are very high because of short generation spans.
 Individual bacteria that are genetically well equipped for the local environment clone
themselves more prolifically than do less fit individuals.
 In contrast, organisms with slower reproduction rates (like humans) create genetic
variation not by novel alleles produced through new mutations, but primarily by sexual
recombination of existing alleles.
Genetic recombination produces new bacterial strains.
 In addition to mutation, genetic recombination generates diversity within bacterial
 Here, recombination is defined as the combining of DNA from two individuals into a
single genome.
 Bacterial recombination occurs through three processes: transformation, transduction, and
 Recombination can be observed when two mutant E. coli strains are combined.
 If each is unable to synthesize one of its required amino acids, neither can grow on a
minimal medium.
 However, if they are combined, numerous colonies will be created that started from
cells that acquired the missing genes for amino acid synthesis from the other strain.
 Some of these capable cells may have resulted from mutation. However, most acquired
the missing genes by genetic recombination.
 Transformation is the alteration of a bacterial cell’s genotype by the uptake of naked,
foreign DNA from the surrounding environment.
 For example, harmless Streptococcus pneumoniae bacteria can be transformed to
pneumonia-causing cells.
 This occurs when a live nonpathogenic cell takes up a piece of DNA that happens to
include the allele for pathogenicity from dead, broken-open pathogenic cells.
 The foreign allele replaces the native allele in the bacterial chromosome by genetic
 The resulting cell is now recombinant, with DNA derived from two different cells.
 Years after transformation was discovered in laboratory cultures, most biologists believed
that the process was too rare and haphazard to play an important role in natural bacterial
 Researchers have since learned that many bacterial species have surface proteins that are
specialized for the uptake of naked DNA.
 These proteins recognize and transport DNA from closely related bacterial species into
the cell, which can then incorporate the foreign DNA into the genome.
 While E. coli lacks this specialized mechanism, it can be induced to take up small
pieces of DNA if cultured in a medium with a relatively high concentration of calcium
 In biotechnology, this technique has been used to introduce foreign DNA into E. coli.
 Transduction occurs when a phage carries bacterial genes from one host cell to another
as a result of aberrations in the phage reproductive cycle.
Biology Chapter Notes
 In generalized transduction, bacterial genes are randomly transferred from one bacterial
cell to another.
 Occasionally, a small piece of the host cell’s degraded DNA, rather than the phage
genome, is packaged within a phage capsid.
 When this phage attaches to another bacterium, it will inject this foreign DNA into its
new host.
 Some of this DNA can subsequently replace the homologous region of the second cell.
 This type of transduction transfers bacterial genes at random.
 Specialized transduction occurs via a temperate phage.
 When the prophage viral genome is excised from the chromosome, it sometimes takes
with it a small region of adjacent bacterial DNA.
 These bacterial genes are injected along with the phage’s genome into the next host
 Specialized transduction only transfers those genes near the prophage site on the
bacterial chromosome.
 Both generalized and specialized transduction use phage as a vector to transfer genes
between bacteria.
 Sometimes known as bacterial “sex,” conjugation transfers genetic material between two
bacterial cells that are temporarily joined.
 The transfer is one-way. One cell (“male”) donates DNA and its “mate” (“female”)
receives the genes.
 A sex pilus from the male initially joins the two cells and creates a cytoplasmic mating
bridge between cells.
 “Maleness,” the ability to form a sex pilus and donate DNA, results from an F (for
fertility) factor as a section of the bacterial chromosome or as a plasmid.
 Plasmids, including the F plasmid, are small, circular, self-replicating DNA
 A genetic element that can replicate either as part of the bacterial chromosome or
independently of it is called an episome.
 Episomes such as the F plasmid can undergo reversible incorporation into the cell’s
 Temperate viruses are also episomes.
 Plasmids usually have only a few genes, which are not required for normal survival and
reproduction of the bacterium.
 However, plasmid genes may be advantageous in stressful conditions.
 The F plasmid facilitates genetic recombination when environmental conditions no
longer favor existing strains.
 The F factor or its F plasmid consists of about 25 genes, most required for the production
of sex pili.
 Cells with either the F factor or the F plasmid are called F+ and they pass this condition
to their offspring.
 Cells lacking either form of the F factor, are called F−, and they function as DNA
 When an F+ and F− cell meet, the F+ cell passes a copy of the F plasmid to the F − cell,
converting it.

Biology Chapter Notes

 The plasmid form of the F factor can become integrated into the bacterial chromosome.
 A cell with the F factor built into its chromosome is called an Hfr cell (for High frequency
of recombination).
 Hfr cells function as males during conjugation.
 The Hfr cell initiates DNA replication at a −point on the F factor DNA and begins to
transfer the DNA copy from that point to its F partner.
 Random movements almost always disrupt conjugation long before an entire copy of the
Hfr chromosome can be passed to the F− cell.
 In the partially diploid cell, the newly acquired DNA aligns with the homologous region
of the F− chromosome.
 Recombination exchanges segments of DNA.
 The resulting recombinant bacterium has genes from two different cells.
 In the 1950s, Japanese physicians began to notice that some bacterial strains had evolved
antibiotic resistance.
 Mutations may reduce the ability of the pathogen’s cell-surface proteins to transport
antibiotics into the bacterial cell.
 Some of these genes code for enzymes that specifically destroy certain antibiotics, like
tetracycline or ampicillin.
 The genes conferring resistance are carried by plasmids, specifically the R plasmid (R for
 When a bacterial population is exposed to an antibiotic, individuals with the R plasmid
will survive and increase in the overall population.
 Because R plasmids also have genes that encode for sex pili, they can be transferred from
one cell to another by conjugation.
 The DNA of a single cell can also undergo recombination due to movement of
transposable genetic elements or transposable elements within the cell’s genome.
 Unlike plasmids or prophages, transposable elements never exist independently but are
always part of chromosomal or plasmid DNA.
 During transposition, the transposable element moves from one location to another in a
cell’s genome.
 In bacteria, the movement may be within the chromosome, from a plasmid to a
chromosome (or vice versa), or between plasmids.
 Transposable elements may move by a “copy and paste” mechanism, in which the
transposable element replicates at its original site, and the copy inserts elsewhere.
 In other words, the transposable element is added at a new site without being lost from
the old site.
 Most transposable elements can move to many alternative locations in the DNA,
potentially moving genes to a site where genes of that sort have never before existed.
 The simplest transposable elements, called insertion sequences, exist only in bacteria.
 An insertion sequence contains a single gene that codes for transposase, an enzyme that
catalyzes movement of the insertion sequence from one site to another within the genome.
 The insertion sequence consists of the transposase gene, flanked by a pair of inverted
repeat sequences.
 The 20 to 40 nucleotides of the inverted repeat on one side are repeated in reverse
along the opposite DNA strand at the other end of the transposable element.
Biology Chapter Notes
 The transposase enzyme recognizes the inverted repeats as the edges of the transposable
 Transposase cuts the transposable elements from its initial site and inserts it into the target
 Insertion sequences cause mutations when they happen to land within the coding sequence
of a gene or within a DNA region that regulates gene expression.
 Insertion sequences account for 1.5% of the E. coli genome, but a mutation in a particular
gene by transposition is rare, occurring about once in every 10 million generations.
 This is about the same rate as spontaneous mutations from external factors.
 Transposable elements longer and more complex than insertion sequences, called
transposons, also move about in the bacterial genome.
 In addition to the DNA required for transposition, transposons include extra genes that
“go along for the ride,” such as genes for antibiotic resistance.
 In some bacterial transposons, the extra genes are sandwiched between two insertion
 While insertion sequences may not benefit bacteria in any specific way, transposons may
help bacteria adapt to new environments.
 For example, a single R plasmid may carry several genes for resistance to different
 This is explained by transposons, which can add a gene for antibiotic resistance to a
plasmid already carrying genes for resistance to other antibiotics.
 The transmission of this composite plasmid to other bacterial cells by cell division or
conjugation can spread resistance to a variety of antibiotics throughout a bacterial
 In an antibiotic-rich environment, natural selection factors bacterial clones that have
built up R plasmids with multiple antibiotic resistance through a series of
 Transposable elements are also important components of eukaryotic genomes.

Concept 18.4 Individual bacteria respond to environmental change by regulating their

gene expression
 An individual bacterium, locked into the genome that it has inherited, can cope with
environmental fluctuations by exerting metabolic control.
 First, cells can vary the number of specific enzyme molecules they make by regulating
gene expression.
 Second, cells can adjust the activity of enzymes already present (for example, by
feedback inhibition).
 The tryptophan biosynthesis pathway demonstrates both levels of control.
 If tryptophan levels are high, some of the tryptophan molecules can inhibit the first
enzyme in the pathway.
 If the abundance of tryptophan continues, the cell can stop synthesizing additional
enzymes in this pathway by blocking transcription of the genes for these enzymes.
 The basic mechanism for this control of gene expression in bacteria, the operon model,
was discovered in 1961 by François Jacob and Jacques Monod.

Biology Chapter Notes

 E. coli synthesizes tryptophan from a precursor molecule in a series of steps, with each
reaction catalyzed by a specific enzyme.
 The five genes coding for these enzymes are clustered together on the bacterial
chromosome, served by a single promoter.
 Transcription gives rise to one long mRNA molecule that codes for all five enzymes in
the tryptophan pathway.
 The mRNA is punctuated with start and stop codons that signal where the coding
sequence for each polypeptide begins and ends.
 A key advantage of grouping genes of related functions into one transcription unit is that a
single “on-off switch” can control a cluster of functionally related genes.
 When an E. coli cell must make tryptophan for itself, all the enzymes are synthesized at
one time.
 The switch is a segment of DNA called an operator.
 The operator, located between the promoter and the enzyme-coding genes, controls the
access of RNA polymerase to the genes.
 The operator, the promoter, and the genes they control constitute an operon.
 By itself, an operon is on and RNA polymerase can bind to the promoter and transcribe
the genes.
 However, if a repressor protein, a product of a regulatory gene, binds to the operator, it
can prevent transcription of the operon’s genes.
 Each repressor protein recognizes and binds only to the operator of a certain operon.
 Regulatory genes are transcribed continuously at low rates.
 Binding by the repressor to the operator is reversible.
 The number of active repressor molecules available determines the on or off mode of
the operator.
 Repressors contain allosteric sites that change shape depending on the binding of other
 In the case of the trp, or tryptophan, operon, when concentrations of tryptophan in the
cell are high, some tryptophan molecules bind as a corepressor to the repressor
 This activates the repressor and turns the operon off.
 At low levels of tryptophan, most of the repressors are inactive, and the operon is
 The trp operon is an example of a repressible operon, one that is inhibited when a specific
small molecule binds allosterically to a regulatory protein.
 In contrast, an inducible operon is stimulated when a specific small molecule interacts
with a regulatory protein.
 In inducible operons, the regulatory protein is active (inhibitory) as synthesized, and
the operon is off.
 Allosteric binding by an inducer molecule makes the regulatory protein inactive, and
the operon is turned on.
 The lac operon contains a series of genes that code for enzymes that play a major role in
the hydrolysis and metabolism of lactose (milk sugar).
 In the absence of lactose, this operon is off, as an active repressor binds to the operator
and prevents transcription.
Biology Chapter Notes
 Lactose metabolism begins with hydrolysis of lactose into its component
monosaccharides, glucose and galactose.
 This reaction is catalyzed by the enzyme ß-galactosidase.
 Only a few molecules of this enzyme are present in an E. coli cell grown in the
absence of lactose.
 If lactose is added to the bacterium’s environment, the number of ß-galactosidase
increases by a thousandfold within 15 minutes.
 The gene for ß-galactosidase is part of the lac operon, which includes two other genes
coding for enzymes that function in lactose metabolism.
 The regulatory gene, lacI, located outside the operon, codes for an allosteric repressor
protein that can switch off the lac operon by binding to the operator.
 Unlike the trp operon, the lac repressor is active all by itself, binding to the operator and
switching the lac operon off.
 An inducer inactivates the repressor.
 When lactose is present in the cell, allolactose, an isomer of lactose, binds to the
 This inactivates the repressor, and the lac operon can be transcribed.
 Repressible enzymes generally function in anabolic pathways, synthesizing end products
from raw materials.
 When the end product is present in sufficient quantities, the cell can allocate its
resources to other uses.
 Inducible enzymes usually function in catabolic pathways, digesting nutrients to simpler
 By producing the appropriate enzymes only when the nutrient is available, the cell
avoids making proteins that have nothing to do.
 Both repressible and inducible operons demonstrate negative control because active
repressors switch off the active form of the repressor protein.
 Positive gene control occurs when an activator molecule interacts directly with the
genome to switch transcription on.
 Even if the lac operon is turned on by the presence of allolactose, the degree of
transcription depends on the concentrations of other substrates.
 If glucose levels are low, then cyclic AMP (cAMP) accumulates.
 The regulatory protein catabolite activator protein (CAP) is an activator of transcription.
 When cAMP is abundant, it binds to CAP, and the regulatory protein assumes its
active shape and can bind to a specific site at the upstream end of the lac promoter.
 The attachment of CAP to the promoter directly stimulates gene expression.
 Thus, this mechanism qualifies as positive regulation.
 The cellular metabolism is biased toward the use of glucose.
 If glucose levels are sufficient and cAMP levels are low (lots of ATP), then the CAP
protein has an inactive shape and cannot bind upstream of the lac promoter.
 The lac operon will be transcribed but at a low level.
 For the lac operon, the presence/absence of lactose (allolactose) determines if the operon
is on or off.

Biology Chapter Notes

 Overall energy levels in the cell determine the level of transcription, a “volume” control,
through CAP.
 CAP works on several operons that encode enzymes used in catabolic pathways.
 If glucose is present and CAP is inactive, then the synthesis of enzymes that catabolize
other compounds is slowed.
 If glucose levels are low and CAP is active, then the genes that produce enzymes that
catabolize whichever other fuel is present will be transcribed at high levels.

Biology Chapter Notes

Chapter 19 Eukaryotic Genomes
Chapter Notes

Overview: How Eukaryotic Genomes Work and Evolve

 Two features of eukaryotic genomes present a major information-processing challenge.

 First, the typical multicellular eukaryotic genome is much larger than that of a
prokaryotic cell.
 Second, cell specialization limits the expression of many genes to specific cells.
 The estimated 25,000 genes in the human genome include an enormous amount of DNA
that does not code for RNA or protein.
 This DNA is elaborately organized.
 Not only is the DNA associated with protein, but also this DNA-protein complex
called chromatin is organized into higher structural levels than the DNA-protein
complex in prokaryotes.

Concept 19.1 Chromatin structure is based on successive levels of DNA packing

 While the single circular chromosome of bacteria is coiled and looped in a complex but
orderly manner, eukaryotic chromatin is far more complex.
 Eukaryotic DNA is precisely combined with large amounts of protein.
 The resulting chromatin undergoes striking changes in the course of the cell cycle.
 During interphase of the cell cycle, chromatin fibers are usually highly extended within
the nucleus.
 As a cell prepares for meiosis, its chromatin condenses, forming a characteristic number
of short, thick chromosomes that can be distinguished with a light microscope.
 Eukaryotic chromosomes contain an enormous amount of DNA relative to their
condensed length.
 Each human chromosome averages about 1.5 × 108 nucleotide pairs.
 If extended, each DNA molecule would be about 4 cm long, thousands of times longer
than the cell diameter.
 This chromosome and 45 other human chromosomes fit into the nucleus.
 This occurs through an elaborate, multilevel system of DNA packing.
 Histone proteins are responsible for the first level of DNA packaging.
 The mass of histone in chromatin is approximately equal to the mass of DNA.
 Their positively charged amino acids bind tightly to negatively charged DNA.
 The five types of histones are very similar from one eukaryote to another, and similar
proteins are found in prokaryotes.
 The conservation of histone genes during evolution reflects their pivotal role in
organizing DNA within cells.
 Unfolded chromatin has the appearance of beads on a string.
 In this configuration, a chromatin fiber is 10 nm in diameter (the 10-nm fiber).
 Each bead of chromatin is a nucleosome, the basic unit of DNA packing.
Biology Chapter Notes
 The “string” between the beads is called linker DNA.
 A nucleosome consists of DNA wound around a protein core composed of two molecules
each of four types of histone: H2A, H2B, H3, and H4.
 The amino acid (N-terminus) of each histone protein (the histone tail) extends outward
from the nucleosome.
 A molecule of a fifth histone, H1, attaches to the DNA near the nucleosome.
 The beaded string seems to remain essentially intact throughout the cell cycle.
 Histones leave the DNA only transiently during DNA replication.
 They stay with the DNA during transcription.
 By changing shape and position, nucleosomes allow RNA-synthesizing polymerases to
move along the DNA.
 The next level of packing is due to the interactions between the histone tails of one
nucleosome and the linker DNA and nucleosomes to either side.
 With the aid of histone H1, these interactions cause the 10-nm to coil to form the 30-
nm chromatin fiber.
 This fiber forms looped domains attached to a scaffold of nonhistone proteins to make up
a 300-nm fiber.
 In a mitotic chromosome, the looped domains coil and fold to produce the characteristic
metaphase chromosome.
 These packing steps are highly specific and precise, with particular genes located in the
same places on metaphase chromosomes.
 Interphase chromatin is generally much less condensed than the chromatin of mitotic
chromosomes, but it shows several of the same levels of higher-order packing.
 Much of the chromatin is present as a 10-nm fiber, and some is compacted into a 30-
nm fiber, which in some regions is folded into looped domains.
 An interphase chromosome lacks an obvious scaffold, but its looped domains seem to
be attached to the nuclear lamina on the inside of the nuclear envelope, and perhaps
also to fibers of the nuclear matrix.
 The chromatin of each chromosome occupies a specific restricted area within the
interphase nucleus.
 Interphase chromosomes have highly condensed areas, heterochromatin, and less
compacted areas, euchromatin.
 Heterochromatin DNA is largely inaccessible to transcription enzymes.
 Looser packing of euchromatin makes its DNA accessible to enzymes and available
for transcription.

Concept 19.2 Gene expression can be regulated at any stage, but the key step is
 Like unicellular organisms, the tens of thousands of genes in the cells of multicellular
eukaryotes are continually turned on and off in response to signals from their internal and
external environments.
 Gene expression must be controlled on a long-term basis during cellular differentiation,
the divergence in form and function as cells in a multicellular organism specialize.
 A typical human cell probably expresses about 20% of its genes at any given time.
Biology Chapter Notes
 Highly specialized cells, such as nerves or muscles, express only a tiny fraction of
their genes.
 Although all the cells in an organism contain an identical genome, the subset of
genes expressed in the cells of each type is unique.
 The differences between cell types are due to differential gene expression, the
expression of different genes by cells with the same genome.
 The genomes of eukaryotes may contain tens of thousands of genes.
 For quite a few species, only a small amount of the DNA—1.5% in humans—codes
for protein.
 Of the remaining DNA, a very small fraction consists of genes for rRNA and tRNA.
 Most of the rest of the DNA seems to be largely noncoding, although researchers have
found that a significant amount of it is transcribed into RNAs of unknown function.
 Problems with gene expression and control can lead to imbalance and diseases, including
 Our understanding of the mechanisms controlling gene expression in eukaryotes has been
enhanced by new research methods, including advances in DNA technology.
 In all organisms, the expression of specific genes is most commonly regulated at
transcription, often in response to signals coming from outside the cell.
 The term gene expression is often equated with transcription.
 With their greater complexity, eukaryotes have opportunities for controlling gene
expression at additional stages.
 Each stage in the entire process of gene expression provides a potential control point
where gene expression can be turned on or off, sped up or slowed down.
 A web of control connects different genes and their products.
 These levels of control include chromatin packing, transcription, RNA processing,
translation, and various alterations to the protein product.
Chromatin modifications affect the availability of genes for transcription.
 In addition to its role in packing DNA inside the nucleus, chromatin organization
regulates gene expression.
 Genes of densely condensed heterochromatin are usually not expressed, presumably
because transcription proteins cannot reach the DNA.
 A gene’s location relative to nucleosomes and to attachment sites to the chromosome
scaffold or nuclear lamina can affect transcription.
 Chemical modifications of chromatin play a key role in chromatin structure and gene
 Chemical modifications of histones play a direct role in the regulation of gene
 The N-terminus of each histone molecule in a nucleosome protrudes outward from the
 These histone tails are accessible to various modifying enzymes, which catalyze the
addition or removal of specific chemical groups.
 Histone acetylation (addition of an acetyl group —COCH3) and deacetylation appear to
play a direct role in the regulation of gene transcription.
 Acetylated histones grip DNA less tightly, providing easier access for transcription
proteins in this region.
Biology Chapter Notes
 Some of the enzymes responsible for acetylation or deacetylation are associated with
or are components of transcription factors that bind to promoters.
 Thus histone acetylation enzymes may promote the initiation of transcription not only
by modifying chromatin structure, but also by binding to and recruiting components of
the transcription machinery.
 DNA methylation is the attachment by specific enzymes of methyl groups (—CH3) to
DNA bases after DNA synthesis.
 Inactive DNA is generally highly methylated compared to DNA that is actively
 For example, the inactivated mammalian X chromosome in females is heavily
 Genes are usually more heavily methylated in cells where they are not expressed.
 Demethylating certain inactive genes turns them on.
 However, there are exceptions to this pattern.
 DNA methylation proteins recruit histone deacetylation enzymes, providing a mechanism
by which DNA methylation and histone deacetylation cooperate to repress transcription.
 In some species, DNA methylation is responsible for long-term inactivation of genes
during cellular differentiation.
 Once methylated, genes usually stay that way through successive cell divisions.
 Methylation enzymes recognize sites on one strand that are already methylated and
correctly methylate the daughter strand after each round of DNA replication.
 This methylation patterns accounts for genomic imprinting in which methylation turns
off either the maternal or paternal alleles of certain genes at the start of development.
 The chromatin modifications just discussed do not alter DNA sequence, and yet they may
be passed along to future generations of cells.
 Inheritance of traits by mechanisms not directly involving the nucleotide sequence is
called epigenetic inheritance.
 Researchers are amassing more and more evidence for the importance of epigenetic
information in the regulation of gene expression.
 Enzymes that modify chromatin structure are integral parts of the cell’s machinery for
regulating transcription.
Transcription initiation is controlled by proteins that interact with DNA and with each
 Chromatin-modifying enzymes provide initial control of gene expression by making a
region of DNA either more available or less available for transcription.
 A cluster of proteins called a transcription initiation complex assembles on the promoter
sequence at the “upstream” end of the gene.
 One component, RNA polymerase II, transcribes the gene, synthesizing a primary
RNA transcript or pre-mRNA.
 RNA processing includes enzymatic addition of a 5’ cap and a poly-A tail, as well as
splicing out of introns to yield a mature mRNA.
 Multiple control elements are associated with most eukaryotic genes.
 Control elements are noncoding DNA segments that regulate transcription by binding
certain proteins.

Biology Chapter Notes

 These control elements and the proteins they bind are critical to the precise regulation
of gene expression in different cell types.
 To initiate transcription, eukaryotic RNA polymerase requires the assistance of proteins
called transcription factors.
 General transcription factors are essential for the transcription of all protein-coding
 Only a few general transcription factors independently bind a DNA sequence such as
the TATA box within the promoter.
 Others in the initiation complex are involved in protein-protein interactions, binding
each other and RNA polymerase II.
 The interaction of general transcription factors and RNA polymerase II with a promoter
usually leads to only a low rate of initiation and production of few RNA transcripts.
 In eukaryotes, high levels of transcription of particular genes depend on the interaction of
control elements with specific transcription factors.
 Some control elements, named proximal control elements, are located close to the
 Distant control elements, enhancers, may be thousands of nucleotides away from the
promoter or even downstream of the gene or within an intron.
 A given gene may have multiple enhancers, each active at a different time or in a different
cell type or location in the organism.
 An activator is a protein that binds to an enhancer to stimulate transcription of a gene.
 Protein-mediated bending of DNA brings bound activators in contact with a group of
mediator proteins that interact with proteins at the promoter.
 This helps assemble and position the initiation complex on the promoter.
 Eukaryotic genes also have repressor proteins to inhibit expression of a gene.
 Eukaryotic repressors can cause inhibition of gene expression by blocking the binding
of activators to their control elements or to components of the transcription machinery
or by turning off transcription even in the presence of activators.
 Some activators and repressors act indirectly to influence chromatin structure.
 Some activators recruit proteins that acetylate histones near the promoters of specific
genes, promoting transcription.
 Some repressors recruit proteins that deacetylate histones, reducing transcription or
silencing the gene.
 Recruitment of chromatin-modifying proteins seems to be the most common
mechanism of repression in eukaryotes.
 The number of nucleotide sequences found in control elements is surprisingly small.
 For many genes, the particular combination of control elements associated with the gene
may be more important than the presence of a single unique control element in regulating
transcription of the gene.
 Even with only a dozen control element sequences, a large number of combinations are
 A particular combination of control elements will be able to activate transcription only
when the appropriate activator proteins are present, such as at a precise time during
development or in a particular cell type.
 The use of different combinations of control elements allows fine regulation of
transcription with a small set of control elements.
Biology Chapter Notes
 In prokaryotes, coordinately controlled genes are often clustered into an operon with a
single promoter and other control elements upstream.
 The genes of the operon are transcribed into a single mRNA and translated together.
 In contrast, very few eukaryotic genes are organized this way.
 Recent studies of the genomes of several eukaryotic species have found that some
coexpressed genes are clustered near each other on the same chromosome.
 Each eukaryotic gene in these clusters has its own promoter and is individually
 The coordinate regulation of clustered genes in eukaryotic cells is thought to involve
changes in the chromatin structure that makes the entire group of genes either available
or unavailable for transcription.
 More commonly, genes coding for the enzymes of a metabolic pathway are scattered over
different chromosomes.
 Coordinate gene expression in eukaryotes depends on the association of a specific control
element or combination of control elements with every gene of a dispersed group.
 A common group of transcription factors binds to all the genes in the group, promoting
simultaneous gene transcription.
 For example, a steroid hormone enters a cell and binds to a specific receptor protein in
the cytoplasm or nucleus, forming a hormone-receptor complex that serves as a
transcription activator.
 Every gene whose transcription is stimulated by that steroid hormone has a control
element recognized by that hormone-receptor complex.
 Other signal molecules control gene expression indirectly by triggering signal-
transduction pathways that lead to activation of transcription.
 Systems for coordinating gene regulation probably arose early in evolutionary history and
evolved by the duplication and distribution of control elements within the genome.
Post-transcriptional mechanisms play supporting roles in the control of gene expression.
 Gene expression may be blocked or stimulated by any posttranscriptional step.
 By using regulatory mechanisms that operate after transcription, a cell can rapidly fine-
tune gene expression in response to environmental changes without altering its
transcriptional patterns.
 RNA processing in the nucleus and the export of mRNA to the cytoplasm provide
opportunities for gene regulation that are not available in bacteria.
 In alternative RNA splicing, different mRNA molecules are produced from the same
primary transcript, depending on which RNA segments are treated as exons and which as
 Regulatory proteins specific to a cell type control intron-exon choices by binding to
regulatory sequences within the primary transcript.
 The life span of an mRNA molecule is an important factor in determining the pattern of
protein synthesis.
 Prokaryotic mRNA molecules may be degraded after only a few minutes.
 Eukaryotic mRNAs typically last for hours, days, or weeks.
 In red blood cells, mRNAs for hemoglobin polypeptides are unusually stable and are
translated repeatedly.

Biology Chapter Notes

 A common pathway of mRNA breakdown begins with enzymatic shortening of the poly-
A tail.
 This triggers the enzymatic removal of the 5’ cap.
 This is followed by rapid degradation of the mRNA by nucleases.
 Nucleotide sequences in the untranslated trailer region at the 3’ end affect mRNA
 Transferring such a sequence from a short-lived mRNA to a normally stable mRNA
results in quick mRNA degradation.
 During the past few years, researchers have found small single-stranded RNA molecules
called microRNAs, or miRNAs, that bind to complementary sequences in mRNA
 miRNAs are formed from longer RNA precursors that fold back on themselves,
forming a long hairpin structure stabilized by hydrogen bonding.
 An enzyme called Dicer cuts the double-stranded RNA into short fragments.
 One of the two strands is degraded. The other miRNA strand associates with a protein
complex and directs the complex to any mRNA molecules with a complementary
 The miRNA-protein complex then degrades the target mRNA or blocks its translation.
 The phenomenon of inhibition of gene expression by RNA molecules is called RNA
interference (RNAi).
 Small interfering RNAs (siRNAs) are similar in size and function to miRNAs and are
generated by similar mechanisms in eukaryotic cells.
 Cellular RNAi pathways lead to the destruction of RNAs and may have originated as a
natural defense against infection by RNA viruses.
 Whatever their origin, RNAi plays an important role in regulating gene expression in
the cell.
 Translation of specific mRNAs can be blocked by regulatory proteins that bind to specific
sequences or structures within the 5’ leader region of mRNA.
 This prevents attachment of ribosomes.
 mRNAs may be stored in egg cells without poly-A tails of sufficient size to allow
translation initiation.
 At the appropriate time during development, a cytoplasmic enzyme adds more A
residues, allowing translation to begin.
 Protein factors required to initiate translation in eukaryotes offer targets for
simultaneously controlling translation of all mRNAs in a cell.
 This allows the cell to shut down translation if environmental conditions are poor (for
example, shortage of a key constituent) or until the appropriate conditions exist (for
example, after fertilization in an egg or during daylight in plants).
 Finally, eukaryotic polypeptides must often be processed to yield functional proteins.
 This may include cleavage, chemical modifications, and transport to the appropriate
 The cell limits the lifetimes of normal proteins by selective degradation.
 Many proteins, like the cyclins in the cell cycle, must be short-lived to function
 Proteins intended for degradation are marked by the attachment of ubiquitin proteins.

Biology Chapter Notes

 Giant protein complexes called proteasomes recognize the ubiquitin and degrade the
tagged protein.
 Mutations making cell cycle proteins impervious to proteasome degradation can lead
to cancer.

Concept 19.3 Cancer results from genetic changes that affect cell cycle control
 Cancer is a disease in which cells escape the control methods that normally regulate cell
growth and division.
 The gene regulation systems that go wrong during cancer are the very same systems
that play important roles in embryonic development, the immune response, and other
biological processes.
 The genes that normally regulate cell growth and division during the cell cycle include
genes for growth factors, their receptors, and the intracellular molecules of signaling
 Mutations altering any of these genes in somatic cells can lead to cancer.
 The agent of such changes can be random spontaneous mutations or environmental
influences such as chemical carcinogens, X-rays, or certain viruses.
 In 1911, Peyton Rous discovered a virus that causes cancer in chickens.
 Since then, scientists have recognized a number of tumor viruses that cause cancer in
various animals, including humans.
 All tumor viruses transform cells into cancer cells through the integration of viral
nucleic acid into host cell DNA.
 Cancer-causing genes, oncogenes, were initially discovered in retroviruses, but close
counterparts, proto-oncogenes, have been found in other organisms.
 The products of proto-oncogenes are proteins that stimulate normal cell growth and
division and play essential functions in normal cells.
 A proto-oncogene becomes an oncogene following genetic changes that lead to an
increase in the proto-oncogene’s protein production or the activity of each protein
 These genetic changes include movements of DNA within the genome, amplification
of the proto-oncogene, and point mutations in the control element of the proto-
 Cancer cells frequently have chromosomes that have been broken and rejoined
 This may translocate a fragment to a location near an active promoter or other control
 Movement of transposable elements may also place a more active promoter near a
proto-oncogene, increasing its expression.
 Amplification increases the number of copies of the proto-oncogene in the cell.
 A point mutation in the promoter or enhancer of a proto-oncogene may increase its
 A point mutation in the coding sequence may lead to translation of a protein that is
more active or longer-lived.
 Mutations to tumor-suppressor genes, whose normal products inhibit cell division, also
contribute to cancer.
Biology Chapter Notes
 Any decrease in the normal activity of a tumor-suppressor protein may contribute to
 Some tumor-suppressor proteins normally repair damaged DNA, preventing the
accumulation of cancer-causing mutations.
 Others control the adhesion of cells to each other or to an extracellular matrix, crucial
for normal tissues and often absent in cancers.
 Still others are components of cell-signaling pathways that inhibit the cell cycle.
Oncogene proteins and faulty tumor-suppressor proteins interfere with normal signaling
 The proteins encoded by many proto-oncogenes and tumor-suppressor genes are
components of cell-signaling pathways.
 Mutations in the products of two key genes, the ras proto-oncogene, and the p53 tumor
suppressor gene occur in 30% and 50% of human cancers, respectively.
 Both the Ras protein and the p53 protein are components of signal-transduction pathways
that convey external signals to the DNA in the cell’s nucleus.
 Ras, the product of the ras gene, is a G protein that relays a growth signal from a growth
factor receptor on the plasma membrane to a cascade of protein kinases.
 At the end of the pathway is the synthesis of a protein that stimulates the cell cycle.
 Many ras oncogenes have a point mutation that leads to a hyperactive version of the
Ras protein that can issue signals on its own, resulting in excessive cell division.
 The p53 gene, named for its 53,000-dalton protein product, is often called the “guardian
angel of the genome.”
 Damage to the cell’s DNA acts as a signal that leads to expression of the p53 gene.
 The p53 protein is a transcription factor for several genes.
 It can activate the p21 gene, which halts the cell cycle.
 It can turn on genes involved in DNA repair.
 When DNA damage is irreparable, the p53 protein can activate “suicide genes” whose
protein products cause cell death by apoptosis.
 A mutation that knocks out the p53 gene can lead to excessive cell growth and cancer.
Multiple mutations underlie the development of cancer.
 More than one somatic mutation is generally needed to produce the changes characteristic
of a full-fledged cancer cell.
 If cancer results from an accumulation of mutations, and if mutations occur throughout
life, then the longer we live, the more likely we are to develop cancer.
 Colorectal cancer, with 135,000 new cases and 60,000 deaths in the United States each
year, illustrates a multistep cancer path.
 The first sign is often a polyp, a small benign growth in the colon lining.
 The cells of the polyp look normal but divide unusually frequently.
 Through gradual accumulation of mutations that activate oncogenes and knock out tumor-
suppressor genes, the polyp can develop into a malignant tumor.
 About a half dozen DNA changes must occur for a cell to become fully cancerous.
 These usually include the appearance of at least one active oncogene and the mutation or
loss of several tumor-suppressor genes.
Biology Chapter Notes
 Since mutant tumor-suppressor alleles are usually recessive, mutations must knock out
both alleles.
 Most oncogenes behave as dominant alleles and require only one mutation.
 In many malignant tumors, the gene for telomerase is activated, removing a natural limit
on the number of times the cell can divide.
 Viruses, especially retroviruses, play a role in about 15% of human cancer cases
 These include some types of leukemia, liver cancer, and cancer of the cervix.
 Viruses promote cancer development by integrating their DNA into that of infected cells.
 By this process, a retrovirus may donate an oncogene to the cell.
 Alternatively, insertion of viral DNA may disrupt a tumor-suppressor gene or convert a
proto-oncogene to an oncogene.
 Some viruses produce proteins that inactivate p53 and other tumor-suppressor proteins,
making the cell more prone to becoming cancerous.
 The fact that multiple genetic changes are required to produce a cancer cell helps explain
the predispositions to cancer that run in some families.
 An individual inheriting an oncogene or a mutant allele of a tumor-suppressor gene
will be one step closer to accumulating the necessary mutations for cancer to develop.
 Geneticists are devoting much effort to finding inherited cancer alleles so that
predisposition to certain cancers can be detected early in life.
 About 15% of colorectal cancers involve inherited mutations, especially to DNA repair
genes or to the tumor-suppressor gene adenomatous polyposis coli, or APC.
 Normal functions of the APC gene include regulation of cell migration and
 Even in patients with no family history of the disease, APC is mutated in about 60%
of colorectal cancers.
 Between 5–10% of breast cancer cases show an inherited predisposition.
 This is the second most common type of cancer in the United States, striking more
than 180,000 women annually and leading to 40,000 annual deaths.
 Mutations to one of two tumor-suppressor genes, BRCA1 and BRCA2, increase the
risk of breast and ovarian cancer.
 A woman who inherits one mutant BRCA1 allele has a 60% probability of developing
breast cancer before age 50 (versus a 2% probability in an individual with two normal
 BRCA1 and BRCA2 are considered tumor-suppressor genes because their wild-type
alleles protect against breast cancer and because their mutant alleles are recessive.
 Recent evidence suggests that the BRCA2 protein is directly involved in repairing
breaks that occur in both strands of DNA.

Concept 19.4 Eukaryotic genomes can have many noncoding DNA sequences in
addition to genes
 Several trends are evident when we compare the genomes of prokaryotes to those of
 There is a general trend from smaller to larger genomes, but with fewer genes in a given
length of DNA.
Biology Chapter Notes
 Humans have 500 to 1,500 times as many base pairs in their genome as most
prokaryotes, but only 5 to 15 times as many genes.
 Most of the DNA in a prokaryote genome codes for protein, tRNA, or rRNA.
 The small amount of noncoding DNA consists mainly of regulatory sequences.
 In eukaryotes, most of the DNA (98.5% in humans) does not code for protein or RNA.
 Gene-related regulatory sequences and introns account for 24% of the human genome.
 Introns account for most of the difference in average length of eukaryotic (27,000
base pairs) and prokaryotic genes (1,000 base pairs).
 Most intergenic DNA is repetitive DNA, present in multiple copies in the genome.
 Transposable elements and related sequences make up 44% of the entire human
 The first evidence for transposable elements came from geneticist Barbara McClintock’s
breeding experiments with Indian corn (maize) in the 1940s and 1950s.
 Eukaryotic transposable elements are of two types: transposons, which move within a
genome by means of a DNA intermediate, and retrotransposons, which move by means of
an RNA intermediate, a transcript of the retrotransposon DNA.
 Transposons can move by a “cut and paste” mechanism, which removes the element
from its original site, or by a “copy and paste” mechanism, which leaves a copy
 Retrotransposons always leave a copy at the original site, since they are initially
transcribed into an RNA intermediate.
 Most transposons are retrotransposons, in which the transcribed RNA includes the code
for an enzyme that catalyzes the insertion of the retrotransposon and may include a gene
for reverse transcriptase.
 Reverse transcriptase uses the RNA molecule originally transcribed from the
retrotransposon as a template to synthesize a double-stranded DNA copy.
 Multiple copies of transposable elements and related sequences are scattered throughout
eukaryotic genomes.
 A single unit is hundreds or thousands of base pairs long, and the dispersed “copies”
are similar but not identical to one another.
 Some of the copies are transposable elements and some are related sequences that have
lost the ability to move.
 Transposable elements and related sequences make up 25–50% of most mammalian
genomes, and an even higher percentage in amphibians and angiosperms.
 In primates, a large portion of transposable element–related DNA consists of a family of
similar sequences called Alu elements.
 These sequences account for approximately 10% of the human genome.
 Alu elements are about 300 nucleotides long, shorter than most functional transposable
elements, and they do not code for protein.
 Many Alu elements are transcribed into RNA molecules.
 However, their cellular function is unknown.
 Repetitive DNA that is not related to transposable elements probably arose by mistakes
that occurred during DNA replication or recombination.
 Repetitive DNA accounts for about 15% of the human genome.

Biology Chapter Notes

 Five percent of the human genome consists of large-segment duplications in which
10,000 to 300,000 nucleotide pairs seem to have been copied from one chromosomal
location to another.
 Simple sequence DNA contains many copies of tandemly repeated short sequences of 15–
500 nucleotides.
 There may be as many as several hundred thousand repetitions of a nucleotide
 Simple sequence DNA makes up 3% of the human genome.
 Much of the genome’s simple sequence DNA is located at chromosomal telomeres and
centromeres, suggesting that it plays a structural role.
 The DNA at centromeres is essential for the separation of chromatids in cell
division and may also help to organize the chromatin within the interphase nucleus.
 Telomeric DNA prevents gene loss as DNA shortens with each round of replication
and also binds proteins that protect the ends of a chromosome from degradation or
attachment to other chromosomes.
Gene families have evolved by duplication of ancestral genes.
 Sequences coding for proteins and structural RNAs compose a mere 1.5% of the human
 If introns and regulatory sequences are included, gene-related DNA makes up 25% of
the human genome.
 In humans, solitary genes present in one copy per haploid set of chromosomes make up
only half of the total coding DNA.
 The rest occurs in multigene families, collections of identical or very similar genes.
 Some multigene families consist of identical DNA sequences that may be clustered
 These code for RNA products or for histone proteins.
 For example, the three largest rRNA molecules are encoded in a single transcription
unit that is repeated tandemly hundreds to thousands of times.
 This transcript is cleaved to yield three rRNA molecules that combine with proteins
and one other kind of rRNA to form ribosomal subunits.
 Two related families of nonidentical genes encode globins, a group of proteins that

 The different versions of each globin subunit are expressed at different times in
development, allowing hemoglobin to function effectively in the changing environment of
the developing animal.

embryonic, fetal, and/or adult stage of development.
 In humans, the embryonic and fetal hemoglobins have higher affinity for oxygen than
do adult forms, ensuring transfer of oxygen from mother to developing fetus.
 Also found in the globin gene family clusters are several pseudogenes, DNA
sequences similar to real genes that do not yield functional proteins.

Biology Chapter Notes

Concept 19.5 Duplications, rearrangements, and mutations of DNA contribute to
genome evolution
 The earliest forms of life likely had a minimal number of genes, including only those
necessary for survival and reproduction.
 The size of genomes has increased over evolutionary time, with the extra genetic material
providing raw material for gene diversification.
 An accident in meiosis can result in one or more extra sets of chromosomes, a condition
known as polyploidy.
 In a polyploid organism, one complete set of genes can provide essential functions for
the organism.
 The genes in the extra set may diverge by accumulating mutations.
 These variations may persist if the organism carrying them survives and
 In this way, genes with novel functions may evolve.
 Errors during meiosis due to unequal crossing over during Prophase I can lead to
duplication of individual genes.
 Slippage during DNA replication can result in deletion or duplication of DNA regions.
 Such errors can lead to regions of repeats, such as simple sequence DNA.
 Major rearrangements of at least one set of genes occur during immune system
 Duplication events can lead to the evolution of genes with related functions, such as the
- -globin gene families.
 A comparison of gene sequences within a multigene family indicates that they all
evolved from one common ancestral globin gene, which was duplicated and diverged
about 450–500 million years ago.
 After the duplication events, the differences between the genes in the globin family arose
from mutations that accumulated in the gene copies over many generations.
 -globin protein was fulfilled by one gene,
while other copies of -globin gene accumulated random mutations.
 Some mutations may have altered the function of the protein product in ways that were
beneficial to the organism without changing its oxygen-carrying function.
 The similarity in the amino acid sequences of th - -globin proteins
supports this model of gene duplication and mutation.
 Random mutations accumulating over time in the pseudogenes have destroyed their
 In other gene families, one copy of a duplicated gene can undergo alterations that lead
to a completely new function for the protein product.
 -lactalbumin are good examples.
 Lysozyme is an enzyme that helps prevent infection by hydrolyzing bacterial cell
 -lactalbumin is a nonenzymatic protein that plays a role in mammalian
milk production.
 Both genes are found in mammals, while only lysozyme is found in birds.
 The two proteins are similar in their amino acids sequences and 3-D structures.

Biology Chapter Notes

 These findings suggest that at some time after the bird and mammalian lineage had
separated, the lysozyme gene underwent a duplication event in the mammalian lineage
but not in the avian lineage.
 Subsequently, one copy of the duplicated lysozyme gene evolved into a gene
-lactalbumin, a protein with a completely different function.
 Rearrangement of existing DNA sequences has also contributed to genome evolution.
 The presence of introns in eukaryotic genes may have promoted the evolution of
new and potentially useful proteins by facilitating the duplication or repositioning
of exons in the genome.
 A particular exon within a gene could be duplicated on one chromosome and
deleted from the homologous chromosome.
 The gene with the duplicated exon would code for a protein with a second copy of
the encoded domain.
 This change in the protein’s structure could augment its function by increasing its
stability or altering its ability to bind a particular ligand.
 Mixing and matching of different exons within or between genes owing to errors in
meiotic recombination is called exon shuffling and could lead to new proteins with
novel combinations of functions.
 The persistence of transposable elements as a large percentage of eukaryotic genomes
suggests that they play an important role in shaping a genome over evolutionary time.
 These elements can contribute to evolution of the genome by promoting
recombination, disrupting cellular genes or control elements, and carrying entire genes
or individual exons to new locations.
 The presence of homologous transposable element sequences scattered throughout the
genome allows recombination to take place between different chromosomes.
 Most of these alterations are likely detrimental, causing chromosomal
translocations and other changes in the genome that may be lethal to the organism.
 Over the course of evolutionary time, an occasional recombination may be
 The movement of transposable elements around the genome can have several direct
 If a transposable element “jumps” into the middle of a coding sequence of a
protein-coding gene, it prevents the normal functioning of that gene.
 If a transposable element inserts within a regulatory sequence, it may increase or
decrease protein production.
 During transposition, a transposable element may transfer genes to a new position
on the genome or may insert an exon from one gene into another gene.
 Transposable elements can lead to new coding sequences when an Alu element
hops into introns to create a weak alternative splice site in the RNA transcript.
 Splicing will usually occur at the regular splice sites, producing the original
 Occasionally, splicing will occur at the new weak site.
 In this way, alternative genetic combinations can be “tried out” while the function
of the original gene product is retained.
 These processes produce no effect or harmful effects in most individual cases.
 However, over long periods of time, the generation of genetic diversity provides
more raw material for natural selection to work on during evolution.

Biology Chapter Notes

Chapter 20 DNA Technology and Genomics
Chapter Notes

Overview: Understanding and Manipulating Genomes

 One of the great achievements of modern science has been the sequencing of the human
genome, which was largely completed by 2003.
 Progress began with the development of techniques for making recombinant DNA, in
which genes from two different sources—and often different species—are combined in
vitro into the same molecule.
 The methods for making recombinant DNA are central to genetic engineering, the direct
manipulation of genes for practical purposes.
 Applications include the introduction of a desired gene into the DNA of a host that will
produce the desired protein.
 DNA technology has launched a revolution in biotechnology, the manipulation of
organisms or their components to make useful products.
 Practices that go back centuries, such as the use of microbes to make wine and cheese
and the selective breeding of livestock, are examples of biotechnology.
 These techniques exploit naturally occurring mutations and genetic recombination.
 Biotechnology based on the manipulation of DNA in vitro differs from earlier
practices by enabling scientists to modify specific genes and move them between
organisms as distinct as bacteria, plants, and animals.
 DNA technology is now applied in areas ranging from agriculture to criminal law, but its
most important achievements are in basic research.

Concept 20.1 DNA cloning permits production of multiple copies of a specific gene or
other DNA segment
 To study a particular gene, scientists needed to develop methods to isolate the small, well-
defined portion of a chromosome containing the gene of interest.
 Techniques for gene cloning enable scientists to prepare multiple identical copies of
gene-sized pieces of DNA.
 One basic cloning technique begins with the insertion of a foreign gene into a bacterial
 E. coli and its plasmids are commonly used.
 First, a foreign gene is inserted into a bacterial plasmid to produce a recombinant DNA
 The plasmid is returned to a bacterial cell, producing a recombinant bacterium, which
reproduces to form a clone of identical cells.
 Every time the bacterium reproduces, the recombinant plasmid is replicated as well.
 Under suitable conditions, the bacterial clone will make the protein encoded by the
foreign gene.
 The potential uses of cloned genes fall into two general categories.
 First, the goal may be to produce a protein product.
Biology Chapter Notes
 For example, bacteria carrying the gene for human growth hormone can produce
large quantities of the hormone.
 Alternatively, the goal may be to prepare many copies of the gene itself.
 This may enable scientists to determine the gene’s nucleotide sequence or provide
an organism with a new metabolic capability by transferring a gene from another
 Most protein-coding genes exist in only one copy per genome, so the ability to clone
rare DNA fragments is very valuable.
Restriction enzymes are used to make recombinant DNA.
 Gene cloning and genetic engineering were made possible by the discovery of restriction
enzymes that cut DNA molecules at specific locations.
 In nature, bacteria use restriction enzymes to cut foreign DNA, to protect themselves
against phages or other bacteria.
 They work by cutting up the foreign DNA, a process called restriction.
 Most restriction enzymes are very specific, recognizing short DNA nucleotide sequences
and cutting at specific points in these sequences.
 Bacteria protect their own DNA by methylating the sequences recognized by these
 Each restriction enzyme cleaves a specific sequence of bases or restriction site.
 These are often a symmetrical series of four to eight bases on both strands running in
opposite directions.
 If the restriction site on one strand is 3’-CTTAAG-5’, the complementary strand is
 Because the target sequence usually occurs (by chance) many times on a long DNA
molecule, an enzyme will make many cuts.
 Copies of a DNA molecule will always yield the same set of restriction fragments
when exposed to a specific enzyme.
 Restriction enzymes cut covalent sugar-phosphate backbones of both strands, often in a
staggered way that creates single-stranded sticky ends.
 These extensions can form hydrogen-bonded base pairs with complementary single-
stranded stretches (sticky ends) on other DNA molecules cut with the same restriction
 These DNA fusions can be made permanent by DNA ligase, which seals the strand by
catalyzing the formation of covalent bonds to close up the sugar-phosphate backbone.
 Restriction enzymes and DNA ligase can be used to make a stable recombinant DNA
molecule, with DNA that has been spliced together from two different organisms.
Eukaryotic genes can be cloned in bacterial plasmids.
 Recombinant plasmids are produced by splicing restriction fragments from foreign DNA
into plasmids.
 The original plasmid used to produce recombinant DNA is called a cloning vector,
defined as a DNA molecule that can carry foreign DNA into a cell and replicate there.
 Bacterial plasmids are widely used as cloning vectors for several reasons.
 They can be easily isolated from bacteria, manipulated to form recombinant plasmids
by in vitro insertion of foreign DNA, and then reintroduced into bacterial cells.

Biology Chapter Notes

 Bacterial cells carrying the recombinant plasmid reproduce rapidly, replicating the
inserted foreign DNA.
 The process of cloning a human gene in a bacterial plasmid can be divided into six steps.
o The first step is the isolation of vector and gene-source DNA.
 The source DNA comes from human tissue cells grown in lab culture.
 The source of the plasmid is typically E. coli.
 This plasmid carries two useful genes, ampR, conferring resistance to the antibiotic
ampicillin and lacZ, encoding the enzyme ß-galactosidase that catalyzes the hydrolysis
of sugar.
 The plasmid has a single recognition sequence, within the lacZ gene, for the restriction
enzyme used.
o DNA is inserted into the vector.
 Both the plasmid and human DNA are digested with the same restriction enzyme. The
enzyme cuts the plasmid DNA at its single restriction site within the lacZ gene. It cuts
the human DNA at many sites, generating thousands of fragments. One fragment
carries the human gene of interest. All the fragments—bacterial and human—have
complementary sticky ends.
o The human DNA fragments are mixed with the cut plasmids, and base-pairing takes
place between complementary sticky ends.
 DNA ligase is added to permanently join the base-paired fragments.
 Some of the resulting recombinant plasmids contain human DNA fragments.
o The recombinant plasmids are mixed with bacteria that are lacZ−, unable to hydrolyze
 This creates a diverse pool of bacteria: some bacteria that have taken up the desired
recombinant plasmid DNA, and other bacteria that have taken up other DNA, both
recombinant and nonrecombinant.
o The transformed bacteria are plated on a solid nutrient medium containing ampicillin
and a molecular mimic of lactose called X-gal.
 Only bacteria that have the ampicillin-resistance (ampR) plasmid will grow.
 Each reproducing bacterium forms a clone by repeating cell divisions, generating a
colony of cells on the agar.
 The lactose mimic in the medium is used to identify plasmids that carry foreign DNA.
 Bacteria with plasmids lacking foreign DNA stain blue when ß-galactosidase from
the intact lacZ gene hydrolyzes X-gal.
 Bacteria with plasmids containing foreign DNA inserted into the lacZ gene are
white because they lack ß-galactosidase.
o Cell clones with the right gene are identified.
 In the final step, thousands of bacterial colonies with foreign DNA must be sorted
through to find those containing the gene of interest.
 One technique, nucleic acid hybridization, depends on base-pairing between the gene
and a complementary sequence, a nucleic acid probe, on another nucleic acid
 The sequence of the RNA or DNA probe depends on knowledge of at least part of
the sequence of the gene of interest.
 A radioactive or fluorescent tag is used to label the probe.
 The probe will hydrogen-bond specifically to complementary single strands of the
desired gene.

Biology Chapter Notes

 After denaturating (separating) the DNA strands in the bacterium, the probe will
bind with its complementary sequence, tagging colonies with the targeted gene.
Cloned genes are stored in DNA libraries.
 In the “shotgun” cloning approach described above, a mixture of fragments from the
entire genome is included in thousands of different recombinant plasmids.
 A complete set of recombinant plasmid clones, each carrying copies of a particular
segment from the initial genome, forms a genomic library.
 The library can be saved and used as a source of other genes or for gene mapping.
 In addition to plasmids, certain bacteriophages are also common cloning vectors for
making genomic libraries.
 Fragments of foreign DNA can be spliced into a phage genome using a restriction
enzyme and DNA ligase.
 An advantage of using phage as vectors is that phage can carry larger DNA inserts than
plasmids can.
 The recombinant phage DNA is packaged in a capsid in vitro and allowed to infect a
bacterial cell.
 Infected bacteria produce new phage particles, each with the foreign DNA.
 A more limited kind of gene library can be developed by starting with mRNA extracted
from cells.
 The enzyme reverse transcriptase is used to make single-stranded DNA transcripts of the
mRNA molecules.
 The mRNA is enzymatically digested, and a second DNA strand complementary to the
first is synthesized by DNA polymerase.
 This double-stranded DNA, called complementary DNA (cDNA), is modified by the
addition of restriction sites at each end.
 Finally, the cDNA is inserted into vector DNA.
 A cDNA library represents that part of a cell’s genome that was transcribed in the
starting cells.
 This is an advantage if a researcher wants to study the genes responsible for
specialized functions of a particular kind of cell.
 By making cDNA libraries from cells of the same type at different times in the life
of an organism, one can trace changes in the patterns of gene expression.
 If a researcher wants to clone a gene but is unsure in what cell type it is expressed or
unable to obtain that cell type, a genomic library will likely contain the gene.
 A researcher interested in the regulatory sequences or introns associated with a gene will
need to obtain the gene from a genomic library.
 These sequences are missing from the processed mRNAs used in making a cDNA
Eukaryote genes can be expressed in prokaryotic host cells.
 A clone can sometimes be screened for a desired gene based on detection of its encoded
 Inducing a cloned eukaryotic gene to function in a prokaryotic host can be difficult.
 One way around this is to insert an expression vector, a cloning vector containing a
highly active prokaryotic promoter, upstream of the restriction site.

Biology Chapter Notes

 The prokaryotic host will then recognize the promoter and proceed to express the
foreign gene that has been linked to it.
 Such expression vectors allow the synthesis of many eukaryotic proteins in prokaryotic
 The presence of long noncoding introns in eukaryotic genes may prevent correct
expression of these genes in prokaryotes, which lack RNA-splicing machinery.
 This problem can be surmounted by using a cDNA form of the gene inserted in a
vector containing a bacterial promoter.
 Molecular biologists can avoid incompatibility problems by using eukaryotic cells as
hosts for cloning and expressing eukaryotic genes.
 Yeast cells, single-celled fungi, are as easy to grow as bacteria and, unlike most
eukaryotes, have plasmids.
 Scientists have constructed yeast artificial chromosomes (YACs) that combine the
essentials of a eukaryotic chromosome (an origin site for replication, a centromere, and
two telomeres) with foreign DNA.
 These chromosome-like vectors behave normally in mitosis and can carry more DNA
than a plasmid.
 Another advantage of eukaryotic hosts is that they are capable of providing the
posttranslational modifications that many proteins require.
 Such modifications may include adding carbohydrates or lipids.
 For some mammalian proteins, the host must be an animal cell to perform the
necessary modifications.
 Many eukaryotic cells can take up DNA from their surroundings, but inefficiently.
 Several techniques facilitate entry of foreign DNA into eukaryotic cells.
 In electroporation, brief electrical pulses create a temporary hole in the plasma
membrane through which DNA can enter.
 Alternatively, scientists can inject DNA into individual cells using microscopically
thin needles.
 Once inside the cell, the DNA is incorporated into the cell’s DNA by natural genetic
The polymerase chain reaction (PCR) amplifies DNA in vitro.
 DNA cloning is the best method for preparing large quantities of a particular gene or other
DNA sequence.
 When the source of DNA is scanty or impure, the polymerase chain reaction (PCR) is
quicker and more selective.
 This technique can quickly amplify any piece of DNA without using cells.
 The DNA is incubated in a test tube with special DNA polymerase, a supply of
nucleotides, and short pieces of single-stranded DNA as a primer.
 PCR can make billions of copies of a targeted DNA segment in a few hours.
 This is faster than cloning via recombinant bacteria.
 In PCR, a three-step cycle—heating, cooling, and replication—brings about a chain
reaction that produces an exponentially growing population of identical DNA molecules.
 The reaction mixture is heated to denature the DNA strands.

Biology Chapter Notes

 The mixture is cooled to allow hydrogen-bonding of short, single-stranded DNA
primers complementary to sequences on opposite sides at each end of the target
 A heat-stable DNA polymerase extends the primers in the 5’  3’ direction.
 If a standard DNA polymerase were used, the protein would be denatured along with the
DNA during the heating step.
 The key to easy PCR automation was the discovery of an unusual DNA polymerase,
isolated from prokaryotes living in hot springs, which can withstand the heat needed to
separate the DNA strands at the start of each cycle.
 PCR is very specific.
 By their complementarity to sequences bracketing the targeted sequence, the primers
determine the DNA sequence that is amplified.
 PCR can make many copies of a specific gene before cloning in cells, simplifying the
task of finding a clone with that gene.
 PCR is so specific and powerful that only minute amounts of partially degraded DNA
need be present in the starting material.
 Occasional errors during PCR replication impose limits to the number of good copies that
can be made when large amounts of a gene are needed.
 Increasingly, PCR is used to make enough of a specific DNA fragment to clone it
merely by inserting it into a vector.
 Devised in 1985, PCR has had a major impact on biological research and technology.
 PCR has amplified DNA from a variety of sources:
 Fragments of ancient DNA from a 40,000-year-old frozen woolly mammoth.
 DNA from footprints or tiny amounts of blood or semen found at the scenes of
violent crimes.
 DNA from single embryonic cells for rapid prenatal diagnosis of genetic disorders.
 DNA of viral genes from cells infected with HIV.

Concept 20.2 Restriction fragment analysis detects DNA differences that affect
restriction sites
 Once we have prepared homogeneous samples of DNA, each containing a large number
of identical segments, we can begin to ask some interesting questions about specific genes
and their functions.
 Does a particular gene differ from person to person?
 Are certain alleles associated with a hereditary disorder?
 Where in the body and when during development is a gene expressed?
 What is the location of a gene in the genome?
 Is expression of a particular gene related to expression of other genes?
 How has a gene evolved, as revealed by interspecific comparisons?
 To answer these questions, we need to know the nucleotide sequence of the gene and its
counterparts in other individuals and species, as well as its expression pattern.
 One indirect method of rapidly analyzing and comparing genomes is gel electrophoresis.
 Gel electrophoresis separates macromolecules—nucleic acids or proteins—on the basis
of their rate of movement through a gel in an electrical field.
Biology Chapter Notes
 Rate of movement depends on size, electrical charge, and other physical properties
of the macromolecules.
 In restriction fragment analysis, the DNA fragments produced by restriction enzyme
digestion of a DNA molecule are sorted by gel electrophoresis.
 When the mixture of restriction fragments from a particular DNA molecule undergoes
electrophoresis, it yields a band pattern characteristic of the starting molecule and the
restriction enzyme used.
 The relatively small DNA molecules of viruses and plasmids can be identified simply
by their restriction fragment patterns.
 The separated fragments can be recovered undamaged from gels, providing pure
samples of individual fragments.
 We can use restriction fragment analysis to compare two different DNA molecules
representing, for example, different alleles of a gene.
 Because the two alleles differ slightly in DNA sequence, they may differ in one or
more restriction sites.
 If they do differ in restriction sites, each will produce different-sized fragments when
digested by the same restriction enzyme.
 In gel electrophoresis, the restriction fragments from the two alleles will produce
different band patterns, allowing us to distinguish the two alleles.
 Restriction fragment analysis is sensitive enough to distinguish between two alleles of a
gene that differ by only one base pair in a restriction site.
 A technique called Southern blotting combines gel electrophoresis with nucleic acid
 Although electrophoresis will yield too many bands to distinguish individually, we can
use nucleic acid hybridization with a specific probe to label discrete bands that derive
from our gene of interest.
 The probe is a radioactive single-stranded DNA molecule that is complementary to the
gene of interest.
 Southern blotting reveals not only whether a particular sequence is present in the
sample of DNA, but also the size of the restriction fragments that contain the sequence.
 One of its many applications is to identify heterozygous carriers of mutant alleles
associated with genetic disease.
 In the example below, we compare genomic DNA samples from three individuals: an
individual who is homozygous for the normal ß-globin allele, a homozygote for sickle-cell
allele, and a heterozygote.
 We combine several molecular techniques to compare DNA samples from three
o We start by adding the same restriction enzyme to each of the three samples to produce
restriction fragments.
o We then separate the fragments by gel electrophoresis.
o We transfer the DNA fragments from the gel to a sheet of nitrocellulose paper, still
separated by size.
 This also denatures the DNA fragments.
o Bathing the sheet in a solution containing a radioactively labeled probe allows the
probe to attach by base-pairing to the DNA sequence of interest.
o We can visualize bands containing the label with autoradiography.

Biology Chapter Notes

 The band pattern for the heterozygous individual will be a combination of the patterns for
the two homozygotes.
Restriction fragment length differences are useful as genetic markers.
 Restriction fragment analysis can be used to examine differences in noncoding DNA as
 Differences in DNA sequence on homologous chromosomes that produce different
restriction fragment patterns are scattered abundantly throughout genomes, including the
human genome.
 A restriction fragment length polymorphism (RFLP or Rif-lip) can serve as a genetic
marker for a particular location (locus) in the genome.
 RFLPs are detected and analyzed by Southern blotting, frequently using the entire genome
as the DNA starting material.
 The probe is complementary to the sequence under consideration.
 Because RFLP markers are inherited in a Mendelian fashion, they can serve as genetic
markers for making linkage maps.
 The frequency with which two RFPL markers—or an RFLP marker and a certain allele
for a gene—are inherited together is a measure of the closeness of the two loci on a

Concept 20.3 Entire genomes can be mapped at the DNA level

 The field of genomics is based on comparisons among whole sets of genes and their
 As early as 1980, Daniel Botstein and his colleagues proposed that the DNA variations
reflected in RFLPs could serve as the basis of an extremely detailed map of the entire
human genome.
 Since then, researchers have used such markers in conjunction with the tools and
techniques of DNA technology to develop detailed maps of the genomes of a number
of species.
 The most ambitious research project made possible by DNA technology has been the
sequencing of the human genome, officially begun as the Human Genome Project in
 This effort was largely completed in 2003 when the nucleotide sequence of the vast
majority of DNA in the human genome was obtained.
 An international, publicly funded consortium of researchers at universities and
research institutes has taken this project through three stages that provided
progressively more detailed views of the human genome: genetic (linkage) mapping,
physical mapping, and DNA sequencing.
 In addition to mapping human DNA, the genomes of other organisms important to
biological research are also being mapped.
 Completed sequences include those of E. coli and other prokaryotes, Saccharomyces
cerevisiae (yeast), Drosophila melanogaster (fruit fly), Mus musculus (mouse), and
 These genomes are providing important insights of general biological significance.
 In mapping a large genome, cytogenetic maps based on karyotyping and fluorescence
hybridization provide a starting point for more detailed mapping.
Biology Chapter Notes
 The first stage is to construct a linkage map of several thousand markers spaced
throughout the chromosomes.
 The order of the markers and the relative distances between them on such a map are
based on recombination frequencies.
 The markers can be genes or any other identifiable sequences in DNA, such as RFLPs
or simple sequence DNA.
 The human map with 5,000 genetic markers enabled researchers to locate other markers,
including genes, by testing for genetic linkage with the known markers.
 The next step was converting the relative distances to some physical measure, usually the
number of nucleotides along the DNA.
 For whole-genome mapping, a physical map is made by cutting the DNA of each
chromosome into identifiable restriction fragments and then determining the original
order of the fragments.
 The key is to make fragments that overlap and then use probes or automated nucleotide
sequencing of the ends to find the overlaps.
 When working with large genomes, researchers carry out several rounds of DNA cutting,
cloning, and physical mapping.
 The first cloning vector is often a yeast artificial chromosome (YAC), which can carry
inserted fragments up to a million base pairs long, or a bacterial artificial
chromosome (BAC), which can carry inserts of 100,000 to 500,000 base pairs.
 After the order of these long fragments has been determined, each fragment is cut into
pieces that are cloned in plasmids or phages, ordered, and finally sequenced.
 The complete nucleotide sequence of a genome is the ultimate map.
 Starting with a pure preparation of many copies of a relatively short DNA fragment,
the nucleotide sequence of the fragment can be determined by a sequencing machine.
 The usual sequencing technique combines DNA labeling, DNA synthesis with special
chain-terminating nucleotides, and high-resolution gel electrophoresis.
 A major thrust of the Human Genome Project has been the development of technology
for faster sequencing and more sophisticated computer software for analyzing and
assembling the partial sequences.
 One common method of sequencing DNA, the Sanger or dideoxyribonucleotide chain-
termination method, is similar to PCR.
 Inclusion of special dideoxyribonucleotides in the reaction mix ensures that rather than
copying the whole template, fragments of various lengths will be synthesized.
 These dideoxyribonucleotides, marked radioactively or fluorescently, terminate
elongation when they are incorporated randomly into the growing strand because they
lack a 3’-OH to attach the next nucleotide.
 The order of these fragments via gel electrophoresis can be interpreted as the nucleotide
 While the public consortium followed a hierarchical, three-stage approach for sequencing
an entire genome, J. Craig Venter decided in 1992 to try a whole-genome shotgun
 This used powerful computers to assemble sequences from random fragments,
skipping the first two steps.
 The worth of his approach was demonstrated in 1995 when he and colleagues reported the
complete sequence of a bacterium.

Biology Chapter Notes

 His private company, Celera Genomics, finished the sequence of Drosophila
melanogaster in 2000.
 In February 2001, Celera and the public consortium separately announced sequencing
more than 90% of the human genome.
 Sequencing of the human genome is now virtually complete, although some gaps remain
to be mapped.
 Areas with repetitive DNA and certain parts of the chromosomes of multicellular
organisms resist detailed mapping by the usual methods.
 On one level, genome sequences of humans and other organisms are simply lists of
nucleotide bases.
 On another level, analyses of these sequences and comparisons between species are
leading to exciting discoveries.

Concept 20.4 Genome sequences provide clues to important biological questions

 Genomics, the study of genomes and their interactions, is yielding new insights into
fundamental questions about genome organization, the regulation of gene expression,
growth and development, and evolution.
 Rather than inferring genotype from phenotype as classical geneticists did, molecular
geneticists can study genes directly.
 This approach poses the challenge of determining phenotype from genotype.
 Starting with a long DNA sequence, how does a researcher recognize genes and
determine their function?
 DNA sequences are collected in computer data banks that are available via the Internet to
researchers everywhere.
 Special software scans the sequences for the telltale signs of protein-coding genes,
looking for start and stop signals, RNA-splicing sites, and other features.
 The software also looks for expressed sequence tags (ESTs), sequences similar to those in
known genes.
 From these clues, researchers collect a list of gene candidates.
 Although genome size increases from prokaryotes to eukaryotes, it does not always
correlate with biological complexity among eukaryotes.
 One flowering plant has a genome 40 times the size of the human genome.
 An organism may have fewer genes than expected from the size of its genome.
 The estimated number of human genes is 25,000 or fewer, only about one-and-a-half
times the number found in the fruit fly.
 This is surprising, given the great diversity of cell types in humans.
 Genes account for only a small fraction of the human genome.
 Much of the enormous amount of noncoding DNA in the human genome consists of
repetitive DNA and unusually long introns.
 By doing more mixing and matching of modular elements, humans—and vertebrates in
general—reach greater complexity than flies or worms.
 Gene expression is regulated in more subtle and complicated ways in vertebrates than
in other organisms.

Biology Chapter Notes

 The typical human gene specifies several different polypeptides by using different
combinations of exons.
 Nearly all human genes contain multiple exons, and an estimated 75% of these
multiexon genes are alternatively spliced.
 Along with this is additional polypeptide diversity via posttranslational processing.
 There are a much greater number of possible interactions between gene products as
a result of greater polypeptide diversity.
 About half of the human genes were already known before the Human Genome Project.
 To determine what the others are and what they may do, scientists compare the sequences
of new gene candidates with those of known genes.
 In some cases, the sequence of a new gene candidate will be similar in part to that of a
known gene, suggesting similar function.
 In other cases, the new sequences will be similar to a sequence encountered before, but
of unknown function.
 In still other cases, the sequence is entirely unlike anything ever seen before.
 About 30% of the E. coli genes are new to us.
 How can scientists determine the function of new genes identified by genome sequencing
and comparative analysis?
 One way to determine their function is to disable the gene and observe the consequences.
 Using in vitro mutagenesis, specific mutations are introduced into a cloned gene,
altering or destroying its function.
 When the mutated gene is returned to the cell, it may be possible to determine the
function of the normal gene by examining the phenotype of the mutant.
 Researchers may put a mutated gene into cells from the early embryo of an organism
to study the role of the gene in development and functioning of the whole organisms.
 In nonmammalian organisms, a simpler and faster method, RNA interference (RNAi),
has been applied to silence the expression of selected genes.
 This method uses synthetic double-stranded RNA molecules matching the sequences
of a particular gene to trigger breakdown of the gene’s mRNA.
 The RNAi technique has had limited success in mammalian cells but has been valuable
in analyzing the functions of genes in nematodes and fruit flies.
 In one study, RNAi was used to prevent expression of 86% of the genes in early
nematode embryos, one gene at a time.
 Analysis of the phenotypes of the worms that developed from these embryos allowed
the researchers to group most of the genes into functional groups.
 A major goal of genomics is to learn how genes act together to produce a functioning
 Part of the explanation for how humans get along with so few genes probably lies in
the unusual complexity of networks of interactions among genes and their products.
 As the sequences of entire genomes of several organisms neared completion, some
researchers began to investigate which genes are transcribed under different situations.
 They also looked for groups of genes that are expressed in a coordinated pattern to
identify global patterns or networks of expression.
 The basic strategy in global expression is to isolate mRNAs from particular cells and use
the mRNA as a template to build cDNA by reverse transcription.
 Each cDNA can be compared to other collections of DNA by hybridization.
Biology Chapter Notes
 This will reveal which genes are active at different developmental stages, in different
tissues, or in tissues in different states of health.
 Automation has allowed scientists to detect and measure the expression of thousands of
genes at one time using DNA microarray assays.
 Tiny amounts of a large number of single-stranded DNA fragments representing
different genes are fixed on a glass slide in a tightly spaced grid (array).
 The array is called a DNA chip.
 The fragments, sometimes representing all the genes of an organism, are tested for
hybridization with various samples of fluorescently labeled cDNA molecules.
 Spots where any of the cDNA hybridizes fluoresce with an intensity indicating the relative
amount of the mRNA that was in the tissue.
 Ultimately, information from microarray assays should provide us a grander view: how
ensembles of genes interact to form a living organism.
 DNA microarray assays are being used to compare cancerous versus noncancerous
 This may lead to new diagnostic techniques and biochemically targeted treatments,
as well as a fuller understanding of cancer.
 The genomes of about 150 species have been completely or almost completely sequenced
by the spring of 2004, with many more in progress.
 Most of these are prokaryotes, including 20 archaean genomes.
 Among the 20 eukaryotic species are vertebrates, invertebrates, and plants.
 Comparisons of genome sequences from different species allow us to determine the
evolutionary relationships even between distantly related organisms.
 The more similar the nucleotide sequences between two species, the more closely related
these species are in their evolutionary history.
 Comparisons of the complete genome sequences of bacteria, archaea, and eukarya support
the theory that these are the three fundamental domains of life.
 Comparative genome studies confirm the relevance of research on simpler organisms to
our understanding of human biology.
 The yeast genome is proving useful in helping us to understand the human genome.
 Comparisons of noncoding sequences in the human genome to those in the much
smaller yeast genome revealed regions with highly conserved sequences that are
important regulatory sequences in both species.
 Several yeast protein-coding genes are so similar to certain human disease genes
that researchers have figured out the functions of the disease genes by studying
their normal yeast counterparts.
 The genomes of two closely related species are likely to be similarly organized.
 Once the sequence and organization of one genome is known, it can greatly accelerate
the mapping of a related genome.
 For example, the mouse genome can be mapped quickly, with the human genome
serving as a guide.
 The small number of gene differences between closely related species makes it easier to
correlate phenotypic differences between species with particular genetic differences.
 One gene that is clearly different in chimps and humans appears to function in speech.
 Researchers may determine what a human disease gene does by studying its normal
counterpart in mice, who share 80% of our genes.
Biology Chapter Notes
 The next step after mapping and sequencing genomes is proteomics, the systematic study
of full protein sets (proteomes) encoded by genomes.
 One challenge is the sheer number of proteins in humans and our close relatives
because of alternative RNA splicing and posttranslational modifications.
 Collecting all the proteins produced by an organism will be difficult because a cell’s
proteins differ with cell type and its state.
 Unlike DNA, proteins are extremely varied in structure and chemical and physical
 Because proteins are the molecules that actually carry out cell activities, we must study
them to learn how cells and organisms function.
 Complete catalogs of genes and proteins will change the discipline of biology
 With such catalogs in hand, researchers are turning their attention to the functional
integration of individual components in biological systems.
 Advances in bioinformatics, the application of computer science and mathematics to
genetic and other biological information, will play a crucial role in dealing with the
enormous mass of data.
 These analyses will provide understanding of the spectrum of genetic variation in humans.
 Because we are all probably descended from a small population living in Africa
150,000 to 200,000 years ago, the amount of DNA variation in humans is small.
 Most of our diversity is in the form of single nucleotide polymorphisms (SNPs),
single base-pair variations.
 In humans, SNPs occur about once in 1,000 bases, meaning that any two humans
are 99.9% identical.
 The locations of the human SNP sites will provide useful markers for studying human
evolution, the differences between human populations, and the migratory routes of
human populations throughout history.
 SNPs and other polymorphisms will be valuable markers for identifying disease genes
and genes that influence our susceptibility to diseases, toxins, or drugs.
 This will change the practice of 21st-century medicine.

Concept 20.5 The practical applications of DNA technology affect our lives in many
DNA technology is reshaping medicine and the pharmaceutical industry.
 Modern biotechnology is making enormous contributions both to the diagnosis of diseases
and in the development of pharmaceutical products.
 The identification of genes whose mutations are responsible for genetic diseases may
lead to ways to diagnose, treat, or even prevent these conditions.
 Susceptibility to many “nongenetic” diseases, from arthritis to AIDS, is influenced by
a person’s genes.
 Diseases of all sorts involve changes in gene expression within the affected genes and
within the patient’s immune system.
 DNA technology can identify these changes and lead to the development of targets for
prevention or therapy.
 PCR and labeled nucleic acid probes can track down the pathogens responsible for
infectious diseases.
Biology Chapter Notes
 For example, PCR can amplify and thus detect HIV DNA in blood and tissue samples,
detecting an otherwise elusive infection.
 RNA cannot be directly amplified by PCR.
 The RNA genome is first converted to double-stranded cDNA by a technique called
RT-PCR, using a probe specific for one of the HIV genes.
 Medical scientists can use DNA technology to identify individuals with genetic diseases
before the onset of symptoms, even before birth.
 Genetic disorders are diagnosed by using PCR and primers corresponding to cloned
disease genes, and then sequencing the amplified product to look for the disease-
causing mutation.
 Cloned disease genes include those for sickle-cell disease, hemophilia, cystic
fibrosis, Huntington’s disease, and Duchenne muscular dystrophy.
 It is even possible to identify symptomless carriers of these diseases.
 It is possible to detect abnormal allelic forms of genes, even in cases in which the gene
has not yet been cloned.
 The presence of an abnormal allele can be diagnosed with reasonable accuracy if a
closely linked RFLP marker has been found.
 The closeness of the marker to the gene makes crossing over between them unlikely,
and the marker and gene will almost always be inherited together.
 Techniques for gene manipulation hold great potential for treating disease by gene
therapy, the alteration of an afflicted individual’s genes.
 A normal allele is inserted into somatic cells of a tissue affected by a genetic disorder.
 For gene therapy of somatic cells to be permanent, the cells that receive the normal
allele must be ones that multiply throughout the patient’s life.
 Bone marrow cells, which include the stem cells that give rise to blood and immune
system cells, are prime candidates for gene therapy.
 A normal allele can be inserted by a retroviral vector into bone marrow cells removed
from the patient.
 If the procedure succeeds, the returned modified cells will multiply throughout the
patient’s life and express the normal gene, providing missing proteins.
 This procedure was used in a 2000 trial involving ten young children with SCID (severe
combined immunodeficiency disease), a genetic disease in which bone marrow cells do
not produce a vital enzyme because of a single defective gene.
 Nine of the children showed significant improvement after two years.
 However, two of the children developed leukemia.
 It was discovered that the retroviral vector used to carry the normal allele into bone
marrow cells had inserted near a gene involved in proliferation and development of
blood cells, causing leukemia.
 The trial has been suspended until researchers learn how to control the location of
insertion of the retroviral vectors.
 Gene therapy poses many technical questions.
 These include regulation of the activity of the transferred gene to produce the
appropriate amount of the gene product at the right time and place.
 In addition, the insertion of the therapeutic gene must not harm other necessary cell
 Gene therapy raises some difficult ethical and social questions.

Biology Chapter Notes

 Some critics suggest that tampering with human genes, even for those with life-
threatening diseases, is wrong.
 They argue that this will lead to the practice of eugenics, a deliberate effort to control
the genetic makeup of human populations.
 The most difficult ethical question is whether we should treat human germ-line cells to
correct the defect in future generations.
 In laboratory mice, transferring foreign genes into egg cells is now a routine procedure.
 Once technical problems relating to similar genetic engineering in humans are solved,
we will have to face the question of whether it is advisable, under any circumstances,
to alter the genomes of human germ lines or embryos.
 Should we interfere with evolution in this way?
 From a biological perspective, the elimination of unwanted alleles from the gene pool
could backfire.
 Genetic variation is a necessary ingredient for the survival of a species as
environmental conditions change with time.
 Genes that are damaging under some conditions could be advantageous under other
conditions, as in the example of the sickle-cell allele.
 DNA technology has been used to create many useful pharmaceuticals, mostly proteins.
 By transferring the gene for a protein into a host that is easily grown in culture, one can
produce large quantities of normally rare proteins.
 By including highly active promoters (and other control elements) into vector DNA,
the host cell can be induced to make large amounts of the product of a gene.
 In addition, host cells can be engineered to secrete a protein, simplifying the task of
 One of the first practical applications of gene splicing was the production of mammalian
hormones and other mammalian regulatory proteins in bacteria.
 These include human insulin, human growth factor (HGF), and tissue plasminogen
 Human insulin, produced by bacteria, is superior for the control of diabetes to the older
treatment of pig or cattle insulin.
 Human growth hormone benefits children with hypopituitarism, a form of dwarfism.
 Tissue plasminogen activator (TPA) helps dissolve blood clots and reduce the risk of
future heart attacks.
 Like many such drugs, it is expensive.
 New pharmaceutical products are responsible for novel ways of fighting diseases that do
not respond to traditional drug treatments.
 One approach is to use genetically engineered proteins that either block or mimic
surface receptors on cell membranes.
 For example, one experimental drug mimics a receptor protein that HIV bonds to when
entering white blood cells. HIV binds to the drug instead and fails to enter the blood
 DNA technology can also be used to produce vaccines, which stimulate the immune
system to defend against specific pathogens.
 A vaccine is a harmless variant or derivative of a pathogen that stimulates the immune
 Traditional vaccines are either killed microbes or attenuated microbes that do not cause
Biology Chapter Notes
 Both are similar enough to the active pathogen to trigger an immune response.
 Recombinant DNA techniques can generate large amounts of a specific protein molecule
normally found on the pathogen’s surface.
 If this protein triggers an immune response against the intact pathogen, then it can be
used as a vaccine.
 Alternatively, genetic engineering can modify the genome of the pathogen to attenuate
 These attenuated microbes are often more effective than a protein vaccine because
they usually trigger a greater response by the immune system.
 Pathogens attenuated by gene-splicing techniques may be safer than the natural
mutants traditionally used.
DNA technology offers forensic, environmental, and agricultural applications.
 In violent crimes, blood, semen, or traces of other tissues may be left at the scene or on
the clothes or other possessions of the victim or assailant.
 If enough tissue is available, forensic laboratories can determine blood type or tissue type
by using antibodies for specific cell surface proteins.
 However, these tests require relatively large amounts of fresh tissue.
 Also, this approach can only exclude a suspect.
 DNA testing can identify the guilty individual with a much higher degree of certainty,
because the DNA sequence of every person is unique (except for identical twins).
 RFPL analysis by Southern blotting can detect similarities and differences in DNA
samples and requires only a tiny amount of blood or other tissue.
 Radioactive probes mark electrophoresis bands that contain certain RFLP markers.
 As few as five markers from an individual can be used to create a DNA fingerprint.
 The probability that two people who are not identical twins have the same DNA
fingerprint is very small.
 DNA fingerprints can be used forensically to present evidence to juries in murder trials.
 An autoradiograph of RFLP bands of samples from a murder victim, the defendant,
and the defendant’s clothes may be consistent with the conclusion that the blood on the
clothes is from the victim, not the defendant.
 The forensic use of DNA fingerprinting extends beyond violent crimes.
 For instance, DNA fingerprinting can be used to settle conclusively questions of
 DNA fingerprinting recently provided strong evidence that Thomas Jefferson fathered
at lease one of the children of his slave Sally Hemings.
 These techniques can also be used to identify the remains of individuals killed in
natural or man-made disasters.
 Variations in the lengths of repeated base sequences are increasingly used as markers in
DNA fingerprinting.
 Such polymorphic genetic loci have repeating units of only a few base pairs and are
highly variable from person to person.
 Individuals may vary in the numbers of simple tandem repeats (STRs) at a locus.
 Restriction fragments with STRs vary in size among individuals because of differences
in STR lengths.
 PCR is often used to amplify selectively particular STRs or other markers before
electrophoresis, especially if the DNA is poor or in minute quantities.
Biology Chapter Notes
 The DNA fingerprint of an individual would be truly unique if it were feasible to perform
restriction fragment analysis on the entire genome.
 In practice, forensic DNA tests focus on only about five tiny regions of the genome.
 The probability that two people will have identical DNA fingerprints in these highly
variable regions is typically between one in 100,000 and one in a billion.
 The exact figure depends on the number of markers and the frequency of those
markers in the population.
 Despite problems that might arise from insufficient statistical data, human error, or
flawed evidence, DNA fingerprinting is now accepted as compelling evidence.
 Increasingly, genetic engineering is being applied to environmental work.
 Scientists are engineering the metabolism of microorganisms to help cope with some
environmental problems.
 For example, genetically engineered microbes that can extract heavy metals from their
environments and incorporate the metals into recoverable compounds may become
important both in mining materials and cleaning up highly toxic mining wastes.
 In addition to the normal microbes that participate in sewage treatment, new microbes
that can degrade other harmful compounds are being engineered.
 Bacterial strains have been developed that can degrade some of the chemicals released
during oil spills.
 For many years, scientists have been using DNA technology to improve agricultural
 DNA technology is now routinely used to make vaccines and growth hormones for
farm animals.
 Transgenic organisms are made by introducing genes from one species into the genome
of another organism.
 An egg cell is removed from a female animal and fertilized in vitro.
 Meanwhile, the desired gene is obtained from another organism and cloned.
 The cloned DNA is injected directly into the nuclei of the fertilized egg.
 Some of the cells integrate the transgene into their genomes and express the foreign
 The engineered embryos are surgically implanted in a surrogate mother.
 Transgenic animals may be created to exploit the attributes of new genes (for example,
genes for faster growth or larger muscles).
 Other transgenic organisms are pharmaceutical “factories”—producers of large amounts
of otherwise rare substances for medical use.
 Transgenic farm mammals may secrete the gene product of interest in their milk.
 Researchers have engineered transgenic chickens that express large quantities of the
transgene’s product in their eggs.
 The human proteins produced by farm animals may or may not be structurally identical to
natural human proteins.
 Therefore, they have to be tested very carefully to ensure that they will not cause
allergic reactions or other adverse effects in patients receiving them.
 In addition, the health and welfare of transgenic farm animals are important issues, as
they often suffer from lower fertility or increased susceptibility to disease.
 Agricultural scientists have engineered a number of crop plants with genes for desirable
Biology Chapter Notes
 These include delayed ripening and resistance to spoilage and disease.
 Because a single transgenic plant cell can be grown in culture to generate an adult
plant, plants are easier to engineer than most animals.
 The Ti plasmid, from the soil bacterium Agrobacterium tumefaciens, is often used to
introduce new genes into plant cells.
 The Ti plasmid normally integrates a segment of its DNA into its host plant and
induces tumors.
 Foreign genes can be inserted into the Ti plasmid (a version that does not cause disease)
using recombinant DNA techniques.
 The recombinant plasmid can be put back into Agrobacterium, which then infects plant
cells, or introduced directly into plant cells.
 Genetic engineering is quickly replacing traditional plant-breeding programs, especially
for useful traits determined by one or a few genes, like herbicide or pest resistance.
 Use of genetically modified crops has reduced the need for chemical insecticides.
 Scientists are using gene transfer to improve the nutritional value of crop plants.
 For example, a transgenic rice plant has been developed that produces yellow grains
containing beta-carotene, which our bodies use to make vitamin A.
 Large numbers of young people in southeast Asia are deficient in vitamin A,
leading to vision impairment and increased disease rates.
 DNA technology has led to new alliances between the pharmaceutical industry and
 Plants can be engineered to produce human proteins for medical use and viral proteins
for use as vaccines.
 Several such “pharm” products are in clinical trials, including vaccines for hepatitis B
and an antibody that blocks the bacteria that cause tooth decay.
 The advantage of pharm plants is that large amounts of proteins might be made more
economically by plants than by cultured cells.
DNA technology raises important safety and ethical questions.
 The power of DNA technology has led to worries about potential dangers.
 Early concerns focused on the possibility that recombinant DNA technology might
create hazardous new pathogens.
 In response, scientists developed a set of guidelines that have become formal government
regulations in the United States and some other countries.
 Strict laboratory procedures are designed to protect researchers from infection by
engineered microbes and to prevent their accidental release.
 Some strains of microorganisms used in recombinant DNA experiments are genetically
crippled to ensure that they cannot survive outside the laboratory.
 Finally, certain obviously dangerous experiments have been banned.
 Today, most public concern centers on genetically modified (GM) organisms used in
 GM organisms have acquired one or more genes (perhaps from another species) by
artificial means.
 Salmon have been genetically modified by addition of a more active salmon growth
hormone gene.
 However, the majority of GM organisms in our food supply are not animals but crop
Biology Chapter Notes
 In 1999, the European Union suspended the introduction of new GM crops pending new
 Early in 2000, negotiators from 130 countries, including the United States, agreed on a
Biosafety Protocol that requires exporters to identify GM organisms present in bulk
food shipments.
 Advocates of a cautious approach fear that GM crops might somehow be hazardous to
human health or cause ecological harm.
 In particular, transgenic plants might pass their new genes to close relatives in nearby
wild areas through pollen transfer.
 Transference of genes for resistance to herbicides, diseases, or insect pests may lead to
the development of wild “superweeds” that would be difficult to control.
 To date there is little good data either for or against any special health or environmental
risks posed by genetically modified crops.
 Today, governments and regulatory agencies are grappling with how to facilitate the use
of biotechnology in agriculture, industry, and medicine while ensuring that new products
and procedures are safe.
 In the United States, all projects are evaluated for potential risks by various regulatory
agencies, including the Food and Drug Administration, Environmental Protection
Agency, the National Institutes of Health, and the Department of Agriculture.
 These agencies are under increasing pressures from some consumer groups.
 As with all new technologies, developments in DNA technology have ethical overtones.
 Who should have the right to examine someone else’s genes?
 How should that information be used?
 Should a person’s genome be a factor in suitability for a job or eligibility for life
 The power of DNA technology and genetic engineering demands that we proceed with
humility and caution.

Biology Chapter Notes

Chapter 21 The Genetic Basis of Development
Chapter Notes

Overview: From Single Cell to Multicellular Organism

 The application of genetic analysis and DNA technology to the study of development has
brought about a revolution in our understanding of how a complex multicellular organism
develops from a single cell.
 In 1995, Swiss researchers identified a gene that functions as a master switch to trigger
the development of the eye in Drosophila.
 A similar gene triggers eye development in mammals.
 Developmental biologists are discovering remarkable similarities in the mechanisms
that shape diverse organisms.
 While geneticists were advancing from Mendel’s laws to an understanding of the
molecular basis of inheritance, developmental biologists were focusing on embryology.
 Embryology is the study of the stages of development leading from fertilized egg to
fully formed organism.
 In recent years, the concepts and tools of molecular genetics have reached a point where a
real synthesis of genetics and developmental biology has been possible.
 When the primary research goal is to understand broad biological principles, the organism
chosen for study is called a model organism.
 Researchers select model organisms that are representative of a larger group, suitable
for the questions under investigation, and easy to grow in the lab.
 For study of the connections between genes and development, suitable model organisms
have short generation times and small genomes that are suitable for genetic analysis.
 Model organisms used in developmental genetics include the fruit fly Drosophila
melanogaster, the nematode Caenorhabditis elegans, the mouse Mus musculus, the
zebra fish Danio rerio, and the plant Arabidopsis thaliana.
 The fruit fly Drosophila melanogaster was first chosen as a model organism by geneticist
T. H. Morgan and intensively studied by generations of geneticists after him.
 The fruit fly is small and easily grown in the laboratory.
 It has a generation time of only two weeks and produces many offspring.
 Embryos develop outside the mother’s body.
 There are vast amounts of information on its genes and other aspects of its biology.
 However, because first rounds of mitosis occur without cytokinesis, parts of its
development are superficially quite different from that of other organisms.
 Sequencing of the Drosophila genome was completed in 2000.
 It has 180 × 106 base pairs (180 Mb) and contains about 13,700 genes.
 The nematode Caenorhabditis elegans normally lives in the soil but is easily grown in
petri dishes.
 Only a millimeter long, it has a simple, transparent body with only a few cell types and
grows from zygote to mature adult in only three and a half days.
 Its genome has been sequenced. It is 97 Mb long and contains an estimated 19,000
 Because individuals are hermaphrodites, it is easy to detect recessive mutations.
Biology Chapter Notes
 Self-fertilization of heterozygotes produces some homozygous recessive offspring
with mutant phenotypes.
 Every adult C. elegans has exactly 959 somatic cells.
 These arise from the zygote in virtually the same way for every individual.
 By following all cell divisions with a microscope, biologists have constructed the
organism’s complete cell lineage, showing the ancestry of every cell in the adult
 The mouse Mus musculus has a long history as a mammalian model of development.
 Much is known about its biology.
 The mouse genome is about 2,600 Mb long with about 25,000 genes, about the same
as the human genome.
 Researchers are adept at manipulating mouse genes to make transgenic mice and mice
in which particular genes are “knocked out” by mutation.
 Mice are complex animals with a genome as large as ours.
 Their embryos develop in the mother’s uterus, hidden from view.
 A second vertebrate model, the zebra fish Danio rerio, has some unique advantages.
 These small fish (2–4 cm long) are easy to breed in the laboratory in large numbers.
 The transparent embryos develop outside the mother’s body.
 Although generation time is two to four months, the early stages of development
proceed quickly.
 By 24 hours after fertilization, most tissues and early versions of the organs have
 After two days, the fish hatches out of the egg case.
 The zebra fish genome is estimated to be 1,700 Mb, and is still being mapped and
 For studying the molecular genetics of plant development, researchers are focusing on a
small weed, Arabidopsis thaliana (a member of the mustard family).
 One plant can grow and produce thousands of progeny after eight to ten weeks.
 A hermaphrodite, each flower makes eggs and sperm.
 For gene manipulation research, scientists can induce cultured cells to take up foreign
DNA (genetic transformation).
 Its relatively small genome, about 118 Mb, contains an estimated 25,500 genes.
 In the development of most multicellular organisms, a single-celled zygote gives rise to
cells of many different types.
 Each type has a different structure and corresponding function.
 Cells of similar types are organized into tissues, tissues into organs, organs into organ
systems, and organ systems into the whole organism.
 Thus, the process of embryonic development must give rise not only to cells of different
types, but also to higher-level structures arranged in a particular way in three dimensions.

Concept 21.1 Embryonic development involves cell division, cell differentiation, and
 An organism arises from a fertilized egg cell as the result of three interrelated processes:
cell division, cell differentiation, and morphogenesis.

Biology Chapter Notes

 Through a succession of mitotic cell divisions, the zygote gives rise to a large number of
 Cell division alone would produce only a great ball of identical cells.
 During development, cells become specialized in structure and function, undergoing cell
 Different kinds of cells are organized into tissues and organs.
 The physical processes that give an organism its shape constitute morphogenesis, the
“creation of form.”
 The processes of cell division, differentiation, and morphogenesis overlap during
 Early events of morphogenesis lay out the basic body plan very early in embryonic
 These include establishing the head of an animal embryo or the roots of a plant
 Later morphogenetic events establish relative locations within smaller regions of the
embryo, such as the digits on a vertebrate limb.
 The overall schemes of morphogenesis in animals and plants are very different.
 In animals, but not in plants, movements of cells and tissues are necessary to transform
the embryo into the characteristic 3-D form of the organism.
 In plants, morphogenesis and growth in overall size are not limited to embryonic and
juvenile periods but occur throughout the life of the plant.
 Apical meristems, perpetually embryonic regions in the tips of shoots and roots, are
responsible for the plant’s continual growth and formation of new organs, such as leaves
and roots.
 In animals, ongoing development in adults is restricted to the generation of cells, such as
blood cells, that must be continually replenished.

Concept 21.2 Different cell types result from differential gene expression in cells with
the same DNA
 During differentiation and morphogenesis, embryonic cells behave and function in ways
different from one another, even though all of them have arisen from the same zygote.
 The differences between cells in a multicellular organism come almost entirely from
differences in gene expression, not differences in the cell’s genomes.
 These differences arise during development, as regulatory mechanisms turn specific genes
off and on.
Different types of cells in an organism have the same DNA.
 Much evidence supports the conclusion that nearly all the cells of an organism have
genomic equivalence—that is, they all have the same genes.
 An important question that emerges is whether genes are irreversibly inactivated during
 One experimental approach to the question of genomic equivalence is to try to generate a
whole organism from differentiated cells of a single type.
 In many plants, whole new organisms can develop from differentiated somatic cells.
Biology Chapter Notes
 During the 1950s, F. C. Steward and his students found that differentiated root cells
removed from the root could grow into normal adult plants when placed in a medium
 These cloning experiments produced genetically identical individuals, popularly called
 The fact that a mature plant cell can dedifferentiate (reverse its function) and give rise to
all the different kinds of specialized cells of a new plant shows that differentiation does
not necessarily involve irreversible changes in the DNA.
 In plants, at least, cells can remain totipotent.
 They retain the zygote’s potential to form all parts of the mature organism.
 Plant cloning is now used extensively in agriculture.
 Differentiated cells from animals often fail to divide in culture, much less develop into a
new organism.
 Animal researchers have approached the genomic equivalence question by replacing the
nucleus of an unfertilized egg or zygote with the nucleus of a differentiated cell.
 The pioneering experiments in nuclear transplantation were carried out by Robert
Briggs and Thomas King in the 1950s and extended later by John Gordon in the 1980s.
 They destroyed or removed the nucleus of a frog egg and transplanted a nucleus from
an embryonic or tadpole cell from the same species into an enucleated egg.
 The ability of the transplanted nucleus to support normal development is inversely related
to the donor’s age.
 Transplanted nuclei from relatively undifferentiated cells from an early embryo lead to
the development of most eggs into tadpoles.
 Transplanted nuclei from fully differentiated intestinal cells lead to fewer than 2% of
the cells developing into normal tadpoles.
 Most of the embryos failed to make it through even the earliest stages of
 Developmental biologists agree on several conclusions about these results.
 First, nuclei do change in some ways as cells differentiate.
 While the DNA sequences do not change, histones may be modified or DNA may
be methylated.
 In frogs and most other animals, nuclear “potency” tends to be restricted more and
more as embryonic development and cell differentiation progress.
 However, chromatin changes are sometimes reversible, and the nuclei of most
differentiated animal cells probably have all the genes required for making an entire
 The ability to clone mammals using nuclei or cells from early embryos has long been
 In 1997, Scottish researchers announced the birth of Dolly, a lamb cloned from an adult
sheep by nuclear transplantation from a differentiated mammary cell.
 The mammary cells were fused with sheep egg cells whose nuclei had been removed.
 The resulting cells divided to form early embryos, which were implanted into surrogate
 One of several hundred implanted embryos completed normal development.

Biology Chapter Notes

 In 2003, Dolly developed a lung disease usually seen in much older sheep and was
 Dolly’s premature death as well as her arthritis led to speculation that her cells were
older than those of a normal sheep, possibly reflecting incomplete reprogramming of
the original transplanted nucleus.
 Since 1997, cloning has been demonstrated in numerous mammals, including mice, cats,
cows, horses, and pigs.
 The possibility of cloning humans raises unprecedented ethical issues.
 In most cases, the goal is to produce new individuals.
 This is known as reproductive cloning.
 These experiments have led to some interesting results.
 Cloned animals in the same species do not look or behave identically.
 Clearly, environmental influences and random phenomena can play a significant role
during development.
 The successful cloning of various mammals raised interest in human cloning.
 In early 2004, South Korean researchers reported success in the first step of
reproductive cloning of humans.
 Nuclei from differentiated human cells were transplanted into unfertilized enucleated
 The eggs divided, and some embryos reached the blastocyst stage before
development was halted.
 In most nuclear transplantation studies, only a small percentage of cloned embryos
develop normally to birth.
 Like Dolly, many cloned animals have various defects, such as obesity, pneumonia,
liver failure, and premature death.
 In the nuclei of fully differentiated cells, a small subset of genes is turned on and the
expression of the rest is repressed.
 This regulation is often the result of epigenetic changes in chromatin, such as the
acetylation of histones or the methylation of DNA.
 Many of these changes must be reversed in the nucleus of the donor animal in order for
genes to be expressed or repressed appropriately for early stages of development.
 Researchers have found that the DNA in embryonic cells from cloned embryos, like
that of differentiated cells, often has more methyl groups than does the DNA in
equivalent cells from uncloned embryos of the same species.
 Because DNA methylation helps regulate gene expression, methylated DNA of donor
nuclei may interfere with the pattern of gene expression necessary for normal
embryonic development.
 Another hot research area involves stem cells.
 A stem cell is a relatively unspecialized cell that can reproduce itself and, under
appropriate conditions, differentiate into specialized cell types.
 In addition to contributing to the study of differentiation, stem cell research has enormous
potential in medicine.
 The ultimate goal is to supply cells for the repair of damaged or diseased organs.
 For example, providing insulin-producing pancreatic cells to diabetics or certain brain
cells to individuals with Parkinson’s disease could cure these diseases.

Biology Chapter Notes

 Many early animal embryos contain totipotent stem cells, which can give rise to
differentiated cells of any type.
 In culture, these embryonic stem cells reproduce indefinitely and can differentiate into
various specialized cells.
 The adult body has various kinds of stem cells, which replace nonreproducing specialized
 Adult stem cells are said to be pluripotent, able to give rise to many, but not all, cell
 For example, stem cells in the bone marrow give rise to all the different kinds of
blood cells.
 The adult brain contains stem cells that continue to produce certain kinds of nerve
 Although adult animals have only tiny numbers of stem cells, scientists are learning to
identify, isolate, and culture these cells from various tissues.
 Under some culture conditions, with the addition of specific growth factors,
cultured adult stem cells can differentiate into multiple types of specialized cells.
 Stem cells from early embryos are somewhat easier to culture than those from adults
and can produce differentiated cells of any type.
 Embryonic stem cells are currently obtained from embryos donated by parents
undergoing fertility treatments, or from long-term cell cultures originally
established with cells isolated from donated embryos.
 Because the cells are derived from human embryos, their use raises ethical and
political issues.
 With the recent cloning of human embryos to the blastocyst stage, scientists might
be able to use these clones as the source of embryonic stem cells in the future.
 When the major aim of cloning is to produce embryonic stem cells to treat disease,
the process is called therapeutic cloning.
 Opinions vary about the morality of therapeutic cloning.

Different cell types make different proteins, usually as a result of transcriptional

 During embryonic development, cells become visibly different in structure and function
as they differentiate.
 The earliest changes that set a cell on a path to specialization show up only at the
molecular level.
 Molecular changes in the embryo drive the process, termed determination, which leads
up to observable differentiation of a cell.
 At the end of this process, an embryonic cell is irreversibly committed to its final fate.
 If a determined cell is experimentally placed in another location in the embryo, it will
differentiate as if it were in its original position.
 The outcome of determination—cell differentiation—is caused by the expression of genes
that encode tissue-specific proteins.
 These give a cell its characteristic structure and function.
 Differentiation begins with the appearance of mRNA and is finally observable in the
microscope as changes in cellular structure.
 In most cases, the pattern of gene expression in a differentiated cell is controlled at the
level of transcription.

Biology Chapter Notes

 Cells produce the proteins that allow them to carry out their specialized roles in the
 For example, lens cells, and only lens cells, devote 80% of their capacity for protein
synthesis to making just one type of protein, crystallin proteins.
 These form transparent fibers that allow the lens to transmit and focus light.
 Similarly, skeletal muscle cells have high concentrations of proteins specific to muscle
tissues, such as a muscle-specific version of the contractile protein myosin and the
structural protein actin.
 They also have membrane receptor proteins that detect signals from nerve cells.
 Muscle cells develop from embryonic precursors that have the potential to develop into a
number of alternative cell types, including cartilage cells, fat cells, or multinucleate
muscle cells.
 As the muscle cells differentiate, they become myoblasts and begin to synthesize
muscle-specific proteins.
 They fuse to form mature, elongated, multinucleate skeletal muscle cells.
 Researchers developed the hypothesis that certain muscle-specific regulatory genes are
active in myoblasts, leading to muscle cell determination.
 To test this, researchers isolated mRNA from cultured myoblasts and used reverse
transcriptase to prepare a cDNA library containing all the genes that are expressed in
cultured myoblasts.
 Transplanting these cloned genes into embryonic precursor cells led to the
identification of several “master regulatory genes” that, when transcribed and
translated, commit the cells to become skeletal muscle.
 One of these master regulatory genes is called myoD, a transcription factor.
 myoD encodes MyoD protein, which binds to specific control elements and stimulates
the transcription of various genes, including some that encode for other muscle-
specific transcription factors.
 These secondary transcription factors activate the muscle protein genes.
 MyoD also stimulates expression of the myoD gene itself, perpetuating its effect in
maintaining the cell’s differentiated state.
 MyoD protein is capable of changing fully differentiated nonmuscle cells into muscle
 However, not all cells will transform.
 Nontransforming cells may lack a combination of regulatory proteins, in addition to
Transcriptional regulation is directed by maternal molecules in the cytoplasm and signals
from other cells.
 Two sources of information “tell” a cell, such as a myoblast or even the zygote, which
genes to express at any given time.
 One source of information is the cytoplasm of the unfertilized egg cell, which contains
RNA and protein molecules encoded by the mother’s DNA.
 Messenger RNA, proteins, other substances, and organelles are distributed unevenly in
the unfertilized egg.
 This impacts embryonic development in many species.
 Maternal substances that influence the course of early development are called
cytoplasmic determinants.
Biology Chapter Notes
 These substances regulate the expression of genes that affect the developmental fate of
the cell.
 After fertilization, the cell nuclei resulting from mitotic division of the zygote are
exposed to different cytoplasmic environments.
 The set of cytoplasmic determinants a particular cell receives helps determine its
developmental fate by regulating expression of the cell’s genes during the course of
cell differentiation.
 The other important source of developmental information is the environment around the
cell, especially signals impinging on an embryonic cell from other nearby embryonic
 In animals, these include contact with cell-surface molecules on neighboring cells and
the binding of growth factors secreted by neighboring cells.
 In plants, the cell-cell junctions known as plasmodesmata allow signal molecules to
pass from one cell to another.
 The synthesis of these signals is controlled by the embryo’s own genes.
 These signal molecules cause induction, triggering observable cellular changes by
causing a change in gene expression in the target cell.

Concept 21.3 Pattern formation in animals and plants results from similar genetic and
cellular mechanisms
 Before morphogenesis can shape an animal or plant, the organism’s body plan must be
 Cytoplasmic determinants and inductive signals contribute to pattern formation, the
development of spatial organization in which the tissues and organs of an organism are
all in their characteristic places.
 Pattern formation continues throughout the life of a plant in the apical meristems.
 In animals, pattern formation is mostly limited to embryos and juveniles.
 Pattern formation begins in the early embryo, when the major axes of an animal and the
root-shoot axis of the plant are established.
 The molecular cues that control pattern formation, positional information, tell a cell
its location relative to the body axes and to neighboring cells.
 They also determine how the cells and their progeny will respond to future molecular
Drosophila development is controlled by a cascade of gene activations.
 Pattern formation has been most extensively studied in Drosophila melanogaster, where
genetic approaches have had spectacular success.
 These studies have established that genes control development and have identified the
key roles that specific molecules play in defining position and directing differentiation.
 Combining anatomical, genetic, and biochemical approaches in the study of
Drosophila development, researchers have discovered developmental principles
common to many other species, including humans.
 Fruit flies and other arthropods have a modular construction, an ordered series of
 These segments make up the three major body parts: the head, thorax (with wings and
legs), and abdomen.
Biology Chapter Notes
 Like other bilaterally symmetrical animals, Drosophila has an anterior-posterior axis
and a dorsal-ventral axis.
 Cytoplasmic determinants in the unfertilized egg provide positional information for
the two developmental axes before fertilization.
 After fertilization, positional information establishes a specific number of correctly
oriented segments and finally triggers the formation of each segment’s characteristic
 The Drosophila egg cell develops in the female’s ovary, surrounded by ovarian cells
called nurse cells and follicle cells that supply the egg cell with nutrients, mRNAs, and
other substances needed for development.
 Development of the fruit fly from egg cell to adult fly occurs in a series of discrete stages.
o Mitosis follows fertilization and egg laying.
 Early mitosis occurs without growth of the cytoplasm and without cytokinesis,
producing one big multinucleate cell.
o At the tenth nuclear division, the nuclei begin to migrate to the periphery of the
o At division 13, the cytoplasm partitions the 6,000 or so nuclei into separate cells.
 The basic body plan—including body axes and segment boundaries—has already been
determined by this time.
 A central yolk nourishes the embryo, and the eggshell continues to protect it.
o Subsequent events in the embryo create clearly visible segments, which at first look
very much alike.
o Some cells move to new positions, organs form, and a wormlike larva hatches from the
 During three larval stages, the larva eats, grows, and molts.
o During the third larval stage, the larva transforms into the pupa enclosed in a case.
o Metamorphosis, the change from larva to adult fly, occurs in the pupal case, and the fly
 Each segment is anatomically distinct, with characteristic appendages.
 The results of detailed anatomical observations of development in several species and
experimental manipulations of embryonic tissues laid the groundwork for understanding
the mechanisms of development.
 In the 1940s, Edward B. Lewis demonstrated that the study of mutants could be used to
investigate Drosophila development.
 He studied bizarre developmental mutations and located the mutations on the fly’s genetic
 This research provided the first concrete evidence that genes somehow direct the
developmental process.
 In the late 1970s, Christiane Nüsslein-Volhard and Eric Weischaus pushed the
understanding of early pattern formation to the molecular level.
 Their goal was to identify all the genes that affect segmentation in Drosophila, but they
faced three problems.
 Because Drosophila has about 13,700 genes, there could be only a few genes affecting
segmentation or so many that the pattern would be impossible to discern.
 Mutations that affect segmentation are likely to be embryonic lethals, leading to death
at the embryonic or larval stage.

Biology Chapter Notes

 Because flies with embryonic lethal mutations never reproduce, they cannot be bred
for study.
 Because of maternal effects on axis formation in the egg, researchers also need to
study maternal genes.
 Nüsslein-Volhard and Wieschaus focused on recessive mutations that could be propagated
in heterozygous flies.
 After mutating flies, they looked for dead embryos and larvae with abnormal
segmentation among the fly’s descendents.
 Through appropriate crosses, they could identify living heterozygotes carrying
embryonic lethal mutations.
 They hoped that the segmental abnormalities would suggest how the affected genes
normally functioned.
 Nüsslein-Volhard and Wieschaus identified 1,200 genes essential for embryonic
 About 120 of these were essential for pattern formation leading to normal
 After several years, they were able to group the genes by general function, map them,
and clone many of them.
 Their results, combined with Lewis’s early work, created a coherent picture of Drosophila
 In 1995, Nüsslein-Volhard, Wieschaus, and Lewis were awarded the Nobel Prize.
Gradients of maternal molecules in the early embryo control axis formation.
 Cytoplasmic determinants establish the axes of the Drosophila body.
 Substances are produced under the direction of maternal effect genes that are
deposited in the unfertilized egg.
 When a maternal effect gene is mutated, the offspring has an abnormal mutant
 In fruit fly development, maternal effect genes encode proteins or mRNA that are placed
in the egg while it is still in the ovary.
 When the mother has a mutated gene, she makes a defective gene product (or none at
all), and her eggs will not develop properly when fertilized.
 These maternal effect genes are also called egg-polarity genes, because they control the
orientation of the egg and consequently the fly.
 One group of genes sets up the anterior-posterior axis, while a second group
establishes the dorsal-ventral axis.
 One of these, the bicoid gene, affects the front half of the body.
 An embryo whose mother has a mutant bicoid gene lacks the front half of its body and has
duplicate posterior structures at both ends.
 This suggests that the product of the mother’s bicoid gene is essential for setting up the
anterior end of the fly.
 It also suggests that the gene’s products are concentrated at the future anterior end.
 This is a specific version of a general gradient hypothesis, in which gradients of
morphogens establish an embryo’s axes and other features.
 Using DNA technology and biochemical methods, researchers were able to clone the
bicoid gene and use it as a probe for bicoid mRNA in the egg.
Biology Chapter Notes
 As predicted, the bicoid mRNA is concentrated at the extreme anterior end of the egg
 After the egg is fertilized, bicoid mRNA is transcribed into bicoid protein, which diffuses
from the anterior end toward the posterior, resulting in a gradient of proteins in the early
 Injections of pure bicoid mRNA into various regions of early embryos results in the
formation of anterior structures at the injection sites as the mRNA is translated into
 The bicoid research is important for three reasons.
o It identified a specific protein required for some of the earliest steps in pattern
o It increased our understanding of the mother’s role in development of an embryo.
 As one developmental biologist put it, “Mom tells Junior which way is up.”
o It demonstrated a key developmental principle that a gradient of molecules can
determine polarity and position in the embryo.
 Gradients of specific proteins determine the posterior end as well as the anterior and also
are responsible for establishing the dorsal-ventral axis.
A cascade of gene activations sets up the segmentation pattern in Drosophila.
 The bicoid protein and other morphogens are transcription factors that regulate the
activity of some of the embryo’s own genes.
 Gradients of these morphogens bring about regional differences in the expression of
segmentation genes, the genes that direct the actual formation of segments after the
embryo’s major axes are defined.
 In a cascade of gene activations, sequential activation of three sets of segmentation genes
provides the positional information for increasingly fine details of the body plan.
 The three sets are called gap genes, pair-rule genes, and segment polarity genes.
 The products of many segmentation genes are transcription factors that directly activate
the next set of genes in the hierarchical scheme of pattern formation.
 Other segmentation proteins operate more indirectly.
 Some are components of cell-signaling pathways, including signal molecules used in
cell-cell communication and the membrane receptors that recognize them.
 Working together, the products of egg-polarity genes such as bicoid regulate the regional
expression of gap genes, which control the localized expression of pair-rule genes, which
in turn activate specific segment polarity genes in different parts of each segment.
 The boundaries and axes of segments are set by this hierarchy of genes (and their
Homeotic genes direct the identity of body parts.
 In a normal fly, structures such as antennae, legs, and wings develop on the appropriate
 The anatomical identity of the segments is controlled by master regulatory genes, the
homeotic genes.
 Discovered by Edward Lewis, these genes specify the types of appendages and other
structures that each segment will form.

Biology Chapter Notes

 Mutations to homeotic genes produce flies with such strange traits as legs growing from
the head in place of antennae.
 Structures characteristic of a particular part of the animal arise in the wrong place.
 Like other developmental genes, the homeotic genes encode transcription factors that
control the expression of genes responsible for specific anatomical structures.
 For example, a homeotic protein made in a thoracic segment may activate genes that
bring about leg development, while a homeotic protein in a certain head segment
activates genes for antennal development.
 A mutant version of this protein may label a segment as “thoracic” instead of “head,”
causing legs to develop in place of antennae.
 Scientists are now working to identify the genes activated by the homeotic proteins—the
genes specifying the proteins that actually build the fly structures.
 Amazingly, many of the molecules and mechanisms that regulate development in the
Drosophila embryo have close counterparts throughout the animal kingdom.
Neighboring cells instruct other cells to form particular structures: cell signaling and
induction in the nematode.
 The development of a multicellular organism requires close communication among cells.
 Signals generated by neighboring nurse cells trigger the localization of bicoid mRNA
in the egg of the Drosophila.
 Once the embryo is truly multicellular, cells signal nearby cells to change in a specific
way, in a process called induction.
 Induction brings about cell differentiation through transcriptional regulation of specific
 The nematode C. elegans has proved to be a very useful model organism for investigating
the roles of cell signaling, induction, and programmed cell death in development.
 Researchers know the entire ancestry of every cell in the body of an adult C. elegans—the
organism’s complete cell lineage.
 As early as the four-cell stage in C. elegans, cell signaling helps direct daughter cells
down appropriate pathways.
 Researchers have combined genetic, biochemical, and embryological approaches to study
the development of the vulva, through which the worm lays its eggs.
 The pathway from fertilized egg to adult nematode involves four larval stages (during
which the larvae look much like smaller versions of the adult) during which this structure
 Already present on the ventral surface of the second-stage larva are six cells from
which the vulva will arise.
 A single cell in the embryonic gonad, the anchor cell, initiates a cascade of signals that
establishes the fate of the six vulval precursor cells.
 If an experimenter destroys the anchor cell with a laser beam, the vulva fails to form
and the precursor cells simply become part of the worm’s epidermis.
 Secreted factors or cell-surface proteins bind to receptors on the recipient cell, initiating
intracellular signal transduction pathways.
 This example illustrates a number of important concepts that apply to development of C.
elegans and many other animals.
 In the developing embryo, sequential inductions drive organ formation.
Biology Chapter Notes
 The effect of an inducer can depend on its concentration.
 Inducers produce their effects via signal transduction pathways similar to those
operating in adult cells.
 The induced cell’s response is often the activation of genes—transcriptional
regulation—that, in turn, establishes a pattern of gene activity characteristic of a
particular kind of differentiated cell.
 Lineage analysis of C. elegans highlights another outcome of cell signaling, programmed
cell death, or apoptosis.
 The timely suicide of cells occurs exactly 131 times in the course of C. elegans’s
normal development.
 At precisely the same points in development, signals trigger the activation of a cascade
of “suicide” proteins in the cells destined to die.
 During apoptosis, a cell shrinks and becomes lobed (called “blebbing”), the nucleus
condenses, and the DNA is fragmented.
 Neighboring cells quickly engulf and digest the membrane-bound remains, leaving no
 Genetic screening of C. elegans has revealed two key apoptosis genes, ced-3 and ced-4
(ced stands for cell death), which encode proteins (Ced-3 and Ced-4) that are essential for
 In C. elegans, a protein in the outer mitochondrial membrane called Ced-9 (the product of
ced-9) is a master regulator of apoptosis.
 ced-9 acts as a brake in the absence of a signal promoting apoptosis.
 When the cell receives an external death signal, Ced-9 is inactivated, allowing both Ced-4
and Ced-3 to be active.
 The apoptosis pathway activates proteases and nucleases to cut up the proteins and
DNA of the cell.
 The main proteases of apoptosis are called caspases.
 In nematodes, Ced-3 is the chief caspase—the main protease of apoptosis.
 Apoptosis is regulated not at the level of transcription or translation, but through changes
in the activity of proteins that are continually present in the cell.
 Apoptosis pathways in humans and other mammals are more complicated.
 Research on mammals has revealed a prominent role for mitochondria in apoptosis.
 Signals from apoptosis pathways or others somehow cause the outer mitochondrial
membrane to leak, releasing proteins that promote apoptosis.
 Surprisingly, these proteins include cytochrome c, which functions in mitochondrial
electron transport in healthy cells but acts as a cell death factor when released from
 Still controversial is whether mitochondria play a central role in apoptosis or only a
subsidiary role.
 A cell must make a life-or-death “decision” by somehow integrating both the “death” and
“life” (growth factor) signals that it receives.
 A built-in cell suicide mechanism is essential to development in all animals.
 Similarities between the apoptosis genes in mammals and nematodes, as well as the
observation that apoptosis occurs in multicellular fungi and unicellular yeast, indicate
that the basic mechanism evolved early in animal evolution.

Biology Chapter Notes

 The timely activation of apoptosis proteins in some cells functions during normal
development and growth in both embryos and adults.
 It is part of the normal development of the nervous system, normal operation of the
immune system, and normal morphogenesis of human hands and feet.
 A low level of apoptosis in developing limbs accounts for the webbed feet of ducks.
 Problems with the cell suicide mechanism may have health consequences, ranging from
minor to serious.
 Failure of normal cell death during morphogenesis of the hands and feet can result in
webbed fingers and toes.
 Researchers are also investigating the possibility that certain degenerative diseases of
the nervous system result from inappropriate activation of the apoptosis genes.
 Others are investigating the possibility that some cancers result from a failure of cell
suicide that normally occurs if the cell has suffered irreparable damage, especially
DNA damage.
 Damaged cells normally generate internal signals that trigger apoptosis.
Plant development depends on cell signaling and transcriptional regulation.
 The genetic analysis of plant development, using model organisms such as Arabidopsis,
has lagged behind that of animal models.
 Biologists are just beginning to understand the molecular basis of plant development.
 In general, cell linage is less important for pattern formation in plants than in animals.
 Many plant cells are totipotent, and their fates depend more on positional information
than on cell lineage.
 Plant development, like that of animals, depends on cell signaling (induction) and
transcriptional regulation.
 The embryonic development of most plants occurs in seeds that are relatively inaccessible
to study.
 However, other important aspects of plant development are observable in plant meristems,
particularly the apical meristems at the tips of shoots.
 These give rise to new organs, such as leaves or the petals of flowers.
 Environmental signals (such as day length or temperature) trigger signal transduction
pathways that convert ordinary shoot meristems to floral meristems.
 A floral meristem is a “bump” with three cell layers, all of which participate in the
formation of a flower with four types of organs: carpels (containing egg cells), petals,
stamens (containing sperm-bearing pollen), and sepals (leaflike structures outside the
 To examine induction of the floral meristem, researchers grafted stems from a mutant
tomato plant onto a wild-type plant and then grew new plants from the shoots at the graft
 Plants homozygous for the mutant allele fasciated (f) produce flowers with an
abnormally large number of organs.
 The new plants were chimeras, organisms with a mixture of genetically different cells.
 Some of the chimeras produced floral meristems in which the three cell layers did not all
come from the same “parent.”
 The number of organs per flower depends on genes of the L3 (innermost) cell layer.
 This induces the L2 and L1 layers to form that number of organs.
Biology Chapter Notes
 In contrast to genes controlling organ number in flowers, genes controlling organ identity
(organ identity genes) determine the types of structure that will grow from a meristem.
 In Arabidopsis and other plants, organ identity genes are analogous to homeotic genes in
animals and are often referred to as plant homeotic genes.
 Mutations cause plant structures to grow in unusual places, such as carpels in the place
of sepals.
 Researchers have identified and cloned a number of floral identity genes, and they are
beginning to determine how they act.
 In plants with a “homeotic” mutation, specific organs are missing or repeated.
 Like the homeotic genes of animals, the organ identity genes of plants encode
transcription factors that regulate specific target genes by binding to their enhancers in
the DNA.

Concept 21.4 Comparative studies help explain how the evolution of development leads
to morphological diversity
 Biologists in the field of evolutionary developmental biology, or “evo-devo,” compare
developmental processes of different multicellular organisms.
 Their aim is to understand how developmental processes have evolved and how
changes in the processes can modify existing organismal features or lead to new ones.
 Biologists are finding that the genomes of related species with strikingly different
forms may have only minor differences in gene sequence or regulation.
 All homeotic genes of Drosophila include a 180-nucleotide sequence called the
homeobox, which specifies a 60-amino-acid homeodomain.
 An identical, or very similar, sequence of nucleotides (often called Hox genes) is found
in many other animals, including humans.
 The vertebrate genes homologous to the homeotic genes of fruit flies have even kept
their chromosomal arrangement.
 Related sequences have been found in the regulatory genes of plants, yeasts, and even
 The homeobox DNA sequence must have evolved very early in the history of life and is
sufficiently valuable that it has been conserved virtually unchanged in animals and plants
for hundreds of millions of years.
 Most, but not all, homeobox-containing genes are homeotic genes that are associated with
 For example, in Drosophila, homeoboxes are present not only in the homeotic genes,
but also in the egg-polarity gene bicoid, in several segmentation genes, and in the
master regulatory gene for eye development.
 The homeobox-encoded homeodomain is part of a protein that binds to DNA when the
protein functions as a transcriptional regulator.
 However, the shape of the homeodomain allows it to bind to any DNA segment.
 Other, more variable, domains of the overall protein determine which genes it will
 Interaction of these latter domains with still other transcription factors helps a
homeodomain-protein recognize specific enhancers in the DNA.
 Proteins with homeodomains probably regulate development by coordinating the
transcription of batteries of developmental genes.
Biology Chapter Notes
 In Drosophila, different combinations of homeobox genes are active in different parts
of the embryo and at different times, leading to pattern formation.
 Many other genes involved in development are highly conserved from species to species.
 These include numerous genes encoding components of signaling pathways.
 How can the same genes be involved in the development of so many different animals?
 In some cases, small changes in regulatory sequences of particular genes can lead to
major changes in body form.
 For example, varying expression of the Hox genes along the body axis produce
different numbers of leg-bearing segments in insects and crustaceans.
 Plants also have homeobox-containing genes.
 However, they do not appear to function as master regulatory switches in plants.
 Other genes appear to be responsible for pattern formation in plants.
There are some basic similarities—and many differences—in the development of plants
and animals.
 The last common ancestor of plants and animals was a single-celled microbe living
hundreds of millions of years ago, so the processes of development evolved independently
in the two lineages.
 Plants have rigid cell walls that prevent cell movement, while morphogenetic
movements are very important in animals.
 Morphogenesis in plants is dependent on differing planes of cell division and selective
cell enlargement.
 Nevertheless, there are some basic similarities of development.
 In both plants and animals, development relies on a cascade of transcriptional
regulators turning on or off genes in a finely tuned series.
 The genes that direct these processes are very different in plants and animals.
 Quite a few of the master regulatory switches in Drosophila are homeobox-containing
Hox genes.
 Those in Arabidopsis belong to the Mads-box family of genes.
 Although homeobox-containing genes can be found in plants and Mads-box genes can be
found in animals, they do not play the same major roles in development in plants and
 The unity of life is reflected in the similarity of biological mechanisms used to establish
body pattern, although the exact genes directing develop may differ.
 The similarities reflect the common ancestry of life on Earth, while the differences have
created the diversity of living organisms.

Biology Chapter Notes

Chapter 22 Descent with Modification: Darwinian View
of Life
Chapter Notes

Overview: Darwin Introduces a Revolutionary Theory

 On November 24, 1859, Charles Darwin published On the Origin of Species by Means of
Natural Selection.
 Darwin’s book drew a cohesive picture of life by connecting what had once seemed a
bewildering array of unrelated facts.
 Darwin made two major points in The Origin of Species:
o Today’s organisms descended from ancestral species that were different from modern
o Natural selection provided a mechanism for this evolutionary change.
 The basic idea of natural selection is that a population can change over time if
individuals that possess certain heritable traits leave more offspring than other
 Natural selection results in evolutionary adaptation, an accumulation of inherited
characteristics that increase the ability of an organism to survive and reproduce in its
 Eventually, a population may accumulate enough change that it constitutes a new species.
 In modern terms, we can define evolution as a change over time in the genetic
composition of a population.
 Evolution also refers to the gradual appearance of all biological diversity.
 Evolution is such a fundamental concept that its study is relevant to biology at every level,
from molecules to ecosystems.
 Evolutionary perspectives continue to transform medicine, agriculture, biotechnology,
and conservation biology.

Concept 22.1 The Darwinian revolution challenged traditional views of a young Earth
inhabited by unchanging species
Western culture resisted evolutionary views of life.
 Darwin’s view of life contrasted with the traditional view of an Earth that was a few
thousand years old, populated by life forms that were created at the beginning and had
remained fundamentally unchanged.
 The Origin of Species challenged a worldview that had been long accepted.
 The Greek philosopher Aristotle (384–322 B.C.E.) opposed any concept of evolution and
viewed species as fixed and unchanging.
 Aristotle believed that all living forms could be arranged on a ladder of increasing
complexity (scala naturae) with perfect, permanent species on every rung.
 The Old Testament account of creation held that species were individually designed by
God and, therefore, perfect.
Biology Chapter Notes
 In the 1700s, natural theology viewed the adaptations of organisms as evidence that the
Creator had designed each species for a purpose.
 Carolus Linnaeus (1707–1778), a Swedish physician and botanist, founded taxonomy, a
system for naming species and classifying species into a hierarchy of increasingly
complex categories.
 Linnaeus developed the binomial system of naming organisms according to genus and
 In contrast to the linear hierarchy of the scala naturae, Linnaeus adopted a nested
classification system, grouping similar species into increasingly general categories.
 For Linnaeus, similarity between species did not imply evolutionary kinship but rather
the pattern of their creation.
 Darwin’s views were influenced by fossils, remains or traces of organisms from the past
mineralized in sedimentary rocks.
 Sedimentary rocks form when mud and sand settle to the bottom of seas, lakes, and
 New layers of sediment cover older ones, creating layers of rock called strata.
 Erosion may later carve through sedimentary rock to expose older strata at the surface.
 Fossils within layers of sedimentary rock show that a succession of organisms have
populated Earth throughout time.
 Paleontology, the study of fossils, was largely developed by the French anatomist
Georges Cuvier (1769–1832).
 In examining rock strata in the Paris Basin, Cuvier noted that the older the strata, the more
dissimilar the fossils from modern life.
 Cuvier recognized that extinction had been a common occurrence in the history of life.
 Instead of evolution, Cuvier advocated catastrophism, speculating that boundaries
between strata were due to local floods or droughts that destroyed the species then
 He suggested that the denuded areas were later repopulated by species immigrating
from unaffected areas.
Theories of geologic gradualism prepared the path for evolutionary biologists.
 In contrast to Cuvier’s catastrophism, Scottish geologist James Hutton (1726–1797)
proposed a theory of gradualism that held that profound geological changes took place
through the cumulative effect of slow but continuous processes identical to those currently
 Thus, valleys were formed by rivers flowing through rocks and sedimentary rocks
were formed from soil particles that eroded from land and were carried by rivers to the
 Later, geologist Charles Lyell (1797–1875) proposed a theory of uniformitarianism,
which held that geological processes had not changed throughout Earth’s history.
 Hutton’s and Lyell’s observations and theories had a strong influence on Darwin.
 First, if geologic changes result from slow, continuous processes rather than sudden
events, then the Earth must be far older than the 6,000 years estimated by theologians
from biblical inference.
 Second, slow and subtle processes persisting for long periods of time can also act on
living organisms, producing substantial change over a long period of time.
Lamarck placed fossils in an evolutionary context.
Biology Chapter Notes
 In 1809, French biologist Jean-Baptiste de Lamarck (1744–1829) published a theory of
evolution based on his observations of fossil invertebrates in the collections of the Natural
History Museum of Paris.
 By comparing fossils and current species, Lamarck found what appeared to be several
lines of descent.
 Each was a chronological series of older to younger fossils, leading to a modern
 He explained his observations with two principles: use and disuse of parts and the
inheritance of acquired characteristics.
 Use and disuse was the concept that body parts that are used extensively become larger
and stronger, while those that are not used deteriorate.
 The inheritance of acquired characteristics stated that modifications acquired during
the life of an organism could be passed to offspring.
 A classic example is the long neck of the giraffe. Lamarck reasoned that the long,
muscular neck of the modern giraffe evolved over many generations as the ancestors of
giraffes reached for leaves on higher branches and passed this characteristic to their
 Lamarck thought that evolutionary change was driven by the innate drive of organisms to
increasing complexity.
 Lamarck’s theory was a visionary attempt to explain the fossil record and the current
diversity of life with recognition of gradual evolutionary change.
 However, modern genetics has provided no evidence that acquired characteristics can
be inherited.
 Acquired traits such as a body builder’s bigger biceps do not change the genes
transmitted through gametes to offspring.

Concept 22.2 In The Origin of Species, Darwin proposed that species change through
natural selection
 Charles Darwin (1809–1882) was born in western England.
 As a boy, he developed a consuming interest in nature.
 When Darwin was 16, his father sent him to the University of Edinburgh to study
 Darwin left Edinburgh without a degree and enrolled at Cambridge University with the
intent of becoming a clergyman.
 At that time, most naturalists and scientists belonged to the clergy and viewed the
world in the context of natural theology.
 Darwin received his B.A. in 1831.
 After graduation Darwin joined the survey ship HMS Beagle as ship naturalist and
conversation companion to Captain Robert FitzRoy.
 FitzRoy chose Darwin because of his education, and because his age and social class
were similar to that of the captain.
Field research helped Darwin frame his view of life.
 The primary mission of the five-year voyage of the Beagle was to chart poorly known
stretches of the South American coastline.

Biology Chapter Notes

 Darwin had the freedom to explore extensively on shore while the crew surveyed the
 He collected thousands of specimens of the exotic and diverse flora and fauna of South
 Darwin explored the Brazilian jungles, the grasslands of the Argentine pampas, the
desolation of Tierra del Fuego near Antarctica, and the heights of the Andes.
 Darwin noted that the plants and animals of South America were very distinct from those
of Europe.
 Organisms from temperate regions of South America more closely resembled those
from the tropics of South America than those from temperate regions of Europe.
 Further, South American fossils, though different from modern species, more closely
resembled modern species from South America than those from Europe.
 While on the Beagle, Darwin read Lyell’s Principles of Geology.
 He experienced geological change firsthand when a violent earthquake rocked the
coast of Chile, causing the coastline to rise by several feet.
 He found fossils of ocean organisms high in the Andes and inferred that the rocks
containing the fossils had been raised there by a series of similar earthquakes.
 These observations reinforced Darwin’s acceptance of Lyell’s ideas and led him to
doubt the traditional view of a young and static Earth.
 Darwin’s interest in the geographic distribution of species was further stimulated by the
Beagle’s visit to the Galapagos, a group of young volcanic islands 900 km west of the
South American coast.
 Darwin was fascinated by the unusual organisms found there.
 After his return to England, Darwin noted that while most of the animal species on the
Galapagos lived nowhere else, they resembled species living on the South American
 He hypothesized that the islands had been colonized by plants and animals from the
mainland that had subsequently diversified on the different islands.
 After his return to Great Britain in 1836, Darwin began to perceive that the origin of new
species and adaptation of species to their environment were closely related processes.
 For example, clear differences in the beaks among the 13 species of finches that
Darwin collected in the Galapagos are adaptations to the specific foods available on
their home islands.
 By the early 1840s, Darwin had developed the major features of his theory of natural
selection as the mechanism for evolution.
 In 1844, he wrote a long essay on the origin of species and natural selection, but he was
reluctant to publish and continued to compile evidence to support his theory.
 In June 1858, Alfred Russel Wallace (1823–1913), a young naturalist working in the East
Indies, sent Darwin a manuscript containing a theory of natural selection essentially
identical to Darwin’s.
 Later that year, both Wallace’s paper and extracts of Darwin’s essay were presented to the
Linnaean Society of London.
 Darwin quickly finished The Origin of Species and published it the next year.
 While both Darwin and Wallace developed similar ideas independently, the theory of
evolution by natural selection is attributed to Darwin because he developed his ideas
earlier and supported the theory much more extensively.
Biology Chapter Notes
 The theory of evolution by natural selection was presented in The Origin of Species
with immaculate logic and an avalanche of supporting evidence.
 Within a decade, The Origin of Species had convinced most biologists that biological
diversity was the product of evolution.
The Origin of Species developed two main ideas: that evolution explains life’s unity and
diversity and that natural selection is the mechanism of adaptive evolution.
 Darwin scarcely used the word evolution in The Origin of Species.
 Instead he used the phrase descent with modification.
 All organisms are related through descent from a common ancestor that lived in the
remote past.
 Over evolutionary time, the descendents of that common ancestor have
accumulated diverse modifications, or adaptations, that allow them to survive and
reproduce in specific habitats.
 Viewed from the perspective of descent with modification, the history of life is like a tree
with multiple branches from a common trunk.
 Closely related species, the twigs on a common branch of the tree, shared the same line
of descent until their recent divergence from a common ancestor.
 Linnaeus recognized that some organisms resemble each other more closely than others,
but he did not explain these similarities by evolution.
 However, his taxonomic scheme fit well with Darwin’s theory.
 To Darwin, the Linnaean hierarchy reflected the branching history of the tree of life.
 Organisms at various taxonomic levels are united through descent from common
 How does natural selection work, and how does it explain adaptation?
 Evolutionary biologist Ernst Mayr has dissected the logic of Darwin’s theory into three
inferences based on five observations.
 Observation #1: All species have such great potential fertility that their population size
would increase exponentially if all individuals that are born reproduced successfully.
 Observation #2: Populations tend to remain stable in size, except for seasonal
 Observation #3: Environmental resources are limited.
 Inference #1: Production of more individuals than the environment can support
leads to a struggle for existence among the individuals of a population, with only a
fraction of the offspring surviving each generation.
 Observation #4: Individuals of a population vary extensively in their characteristics; no
two individuals are exactly alike.
 Observation #5: Much of this variation is heritable.
 Inference #2: Survival in the struggle for existence is not random, but depends in
part on inherited traits. Those individuals whose inherited traits are best suited for
survival and reproduction in their environment are likely to leave more offspring
than less fit individuals.
 Inference #3: This unequal ability of individuals to survive and reproduce will lead
to a gradual change in a population, with favorable characteristics accumulating
over generations.
 A 1798 essay on human population by Thomas Malthus heavily influenced Darwin’s
views on “overreproduction.”
Biology Chapter Notes
 Malthus contended that much human suffering—disease, famine, homelessness, war—
was the inescapable consequence of the potential for human populations to increase
faster than food supplies and other resources.
 The capacity to overproduce seems to be a characteristic of all species.
 Only a tiny fraction of offspring produced complete their development and reproduce
successfully to leave offspring of their own.
 In each generation, environmental factors filter heritable variations, favoring some over
 Differential reproductive success—whereby organisms with traits favored by the
environment produce more offspring than do organisms without those traits—results in
the favored traits being disproportionately represented in the next generation.
 This increasing frequency of the favored traits in a population is evolutionary change.
 Darwin’s views on the role of environmental factors in the screening of heritable variation
were heavily influenced by artificial selection.
 Humans have modified a variety of domesticated plants and animals over many
generations by selecting individuals with the desired traits as breeding stock.
 If artificial selection can achieve so much change in a relatively short period of time,
Darwin reasoned, then natural selection should be capable of considerable
modification of species over thousands of generations.
 Darwin’s main ideas can be summarized in three points.
 Natural selection is differential success in reproduction (unequal ability of individuals
to survive and reproduce) that results from individuals that vary in heritable traits and
their environment.
 The product of natural selection is the increasing adaptation of organisms to their
 If an environment changes over time, or if individuals of a species move to a new
environment, natural selection may result in adaptation to the new conditions,
sometimes giving rise to a new species in the process.
 Three important points need to be emphasized about evolution through natural
o Although natural selection occurs through interactions between individual organisms
and their environment, individuals do not evolve. A population (a group of
interbreeding individuals of a single species that share a common geographic area) is
the smallest group that can evolve. Evolutionary change is measured as changes in
relative proportions of heritable traits in a population over successive generations.
o Natural selection can act only on heritable traits, traits that are passed from organisms
to their offspring. Characteristics acquired by an organism during its lifetime may
enhance its survival and reproductive success, but there is no evidence that such
characteristics can be inherited by offspring.
o Environmental factors vary from place to place and from time to time. A trait that is
favorable in one environment may be useless or even detrimental in another
 Darwin envisioned the diversity of life as evolving by a gradual accumulation of minute
changes through the actions of natural selection operating over vast spans of time.

Concept 22.3 Darwin’s theory explains a wide range of observations

Biology Chapter Notes

 The power of evolution by natural selection as a unifying theory is its versatility as a
natural explanation for diverse data from many fields of biology.
 We will consider two examples of natural selection as a mechanism of evolution in
 Our first example concerns differential predation and guppy populations.
 Guppies (Poecilia reticulata) live in the wild in pools in the Aripo River system in
 John Endler and David Reznick have been studying these small fish for more than a
 The researchers observed significant differences between populations of guppies that live
in different pools in the river system.
 Populations varied in the average age and size of sexual maturity.
 These variations were correlated to the type of predator present in each pool.
 In some pools, the main predator is the small killifish, which eats juvenile guppies.
 In other pools, the major predator is the large pike-cichlid, which eats adult guppies.
 Guppies in populations preyed on by pike-cichlids begin reproducing at a younger age
and are smaller at maturity than guppies in populations preyed on by killifish.
 To test whether these differences are due to natural selection, Reznick and Endler
introduced guppies from pike-cichlid locations to new pools that contained killifish but no
 After eleven years, the transplanted guppies were, on average, 14% heavier at maturity
than the nontransplanted populations.
 Their average age at maturity had also increased.
 These results support the hypothesis that natural selection caused the changes in the
transplanted population.
 Because pike-cichlids prey mainly on reproductively mature adults, the chance that a
guppy will survive to reproduce several times is low.
 The guppies with the greatest reproductive success in ponds with pike-cichlid
predators are those that mature at a young age and small size, enabling them to
produce at least one brood before growing to a size preferred by pike-cichlids.
 In ponds with killifish predators, guppies that survive early predation can grow slowly
and produce many broods of young.
 A second example of ongoing natural selection is the evolution of drug-resistant HIV
(human immunodeficiency virus).
 Researchers have developed numerous drugs to combat HIV, but using these medications
selects for viruses resistant to the drugs.
 A few drug-resistant viruses may be present by chance at the beginning of treatment.
 The drug-resistant pathogens are more likely to survive treatment and pass on the
genes that enable them to resist the drug to their offspring.
 As a result, the frequency of drug resistance in the viral population rapidly increases.
 Scientists designed the drug 3TC to interfere with reverse transcriptase, the enzyme that
HIV uses to copy its RNA genome into the DNA of the host cell.
 Because 3TC is similar in shape to the cytosine nucleotide of DNA, HIV’s reverse
transcriptase incorporates 3TC into its growing DNA chain instead of cytosine. This
error terminates elongation of DNA and thus prevents HIV reproduction.

Biology Chapter Notes

 3TC-resistant varieties of HIV have a form of reverse transcriptase that can
discriminate between cytosine and 3TC.
 These viruses have no advantage in the absence of 3TC. In fact, they replicate more
slowly than viruses with normal reverse transcriptase.
 Once 3TC is added to their environment, it becomes a powerful selective agent,
favoring reproduction of resistant individuals.
 The examples of the guppies and HIV highlight two important points about natural
 First, natural selection is an editing mechanism, not a creative force. It can only act on
existing variation in the population; it cannot create favorable traits.
 Second, natural selection favors traits that increase fitness in the current, local
environment. What is adaptive in one situation is not adaptive in another.
 For example, guppies that mature at an early age and small size are at an advantage
in a pool with pike-cichlids, but at a disadvantage in a pool with killifish.
 In the absence of 3TC, HIV with the modified form of reverse transcriptase grows
more slowly than HIV with normal reverse transcriptase.
Evidence of evolution pervades biology.
 In the cases described, natural selection brought about change rapidly enough that it could
be observed directly.
 Darwin’s theory also provides a cohesive explanation for observations in the fields of
anatomy, embryology, molecular biology, biogeography, and paleontology.
 Descent with modification can explain why certain traits in related species have an
underlying similarity even if they have very different functions.
 Similarity in characteristic traits from common ancestry is known as homology.
 For example, the forelimbs of human, cats, whales, and bats share the same skeletal
elements, even though the appendages have very different functions.
 These forelimbs are homologous structures that represent variations on the ancestral
tetrapod forelimb.
 Homologies that are not obvious in adult organisms may become evident when we look at
embryonic development.
 For example, all vertebrate embryos have structures called pharyngeal pouches in their
throat at some stage in their development.
 These embryonic structures develop into very different, but still homologous, adult
structures, such as the gills of fish or the Eustacian tubes that connect the middle ear
with the throat in mammals.
 Some of the most interesting homologous structures are vestigial organs, structures that
have marginal, if any, importance to a living organism, but which had important functions
in the organism’s ancestors.
 For example, the skeletons of some snakes and of fossil whales retain vestiges of the
pelvis and leg bones of walking ancestors.
 Comparative anatomy confirms that evolution is a remodeling process, an alteration of
existing structures.
 Because evolution can only modify existing structures and functions, it may produce
structures that are less than perfect.
 For example, the back and knee problems of bipedal humans are an unsurprising
outcome of adapting structures originally evolved to support four-legged mammals.
Biology Chapter Notes
 Similarities among organisms can also be seen at the molecular level.
 For example, all species of life have the same basic genetic machinery of RNA and
DNA, and the genetic code is essentially universal.
 The ubiquity of the genetic code provides evidence of a single origin of life.
 It is likely that the language of the genetic code has been passed along through all the
branches of the tree of life ever since its inception in an early life form.
 Homologies mirror the taxonomic hierarchy of the tree of life.
 Some homologies, such as the genetic code, are shared by all living things because
they arose in the deep ancestral past.
 Other homologies that evolved more recently are shared only by smaller branches of
the tree of life.
 For example, all tetrapods (amphibians, reptiles, birds, and mammals) share the
same five-digit limb structure.
 Thus homologies are found in a nested pattern, with all life sharing the deepest layer
and each smaller group adding new homologies to those they share with the larger
 This hierarchical pattern of homology is exactly what we would expect if life evolved
and diversified from a common ancestor.
 Anatomical resemblances among species are generally reflected in their genes (DNA) and
gene products (proteins).
 If hierarchies of homology reflect evolutionary history, then we should expect to find
similar patterns whether we are comparing molecules or bones.
 Different kinds of homologies will coincide because they have followed the same
branching pattern through evolutionary history.
 The geographical distribution of species—biogeography—first suggested evolution to
 Species tend to be more closely related to other species from the same area than to
other species with the same way of life that live in different areas.
 Consider Australia, home to a unique group of marsupial mammals, which
complete their development in an external pouch.
 Some marsupial mammals superficially resemble eutherian mammals (which
complete their development in the uterus) from other continents.
 For example, the Australian sugar glider and North American flying squirrel are
adapted to the same mode of life and look somewhat similar.
 However, the sugar glider shares more characteristics with other Australian
marsupials than with the flying squirrel.
 The resemblance between the two gliders is an example of convergent evolution.

 Islands and island archipelagos have provided strong evidence of evolution.

 Islands generally have many species of plants and animals that are endemic, found
nowhere else in the world.
 As Darwin observed when he reassessed his collections from the Beagle’s voyage, these
endemic species are typically more closely related to species living on the nearest
mainland (despite different environments) than to species from other island groups.
 In island chains, or archipelagos, individual islands may have different, but related,
species. The first mainland invaders reached one island and then evolved into several new
species as they colonized other islands in the archipelago.

Biology Chapter Notes

 Several well-investigated examples of this phenomenon include the diversification of
finches on the Galapagos Islands and fruit flies (Drosophila) on the Hawaiian
 The succession of fossil forms is consistent with what is known from other types of
evidence about the major branches of descent in the tree of life.
 For example, considerable evidence suggests that prokaryotes are the ancestors of all
life and should precede all eukaryotes in the fossil record. In fact, the oldest known
fossils are prokaryotes.
 Fossil fishes predate all other vertebrates, with amphibians next, followed by reptiles,
then mammals and birds.
 This is consistent with the history of vertebrate descent supported by many other types
of evidence.
 The Darwinian view of life also predicts that evolutionary transitions should leave signs in
the fossil record.
 Paleontologists have discovered fossils of many such transitional forms that link ancient
organisms to modern species.
 For example, fossil evidence documents the origin of birds from one branch of
 Recent discoveries include fossilized whales that link these aquatic mammals to their
terrestrial ancestors.
What is theoretical about the Darwinian view of life?
 Some people dismiss the Darwinian view as “just a theory.”
 As we have seen, Darwin’s explanation makes sense of large amounts of data.
 The effects of natural selection can be observed in nature.
 What is theoretical about evolution?
 The term theory has a very different meaning in science than in everyday use.
 The word theory in colloquial use is closer to the concept of a hypothesis in science.
 In science, a theory is more comprehensive than a hypothesis, accounting for many
observations and data and attempting to explain and integrate a great variety of
 A unifying theory does not become widely accepted unless its predictions stand up to
thorough and continual testing by experiments and additional observation.
 That has certainly been the case with the theory of evolution by natural selection.
 Scientists continue to test this theory.
 For example, many evolutionary biologists now question whether natural selection is
the only mechanism responsible for evolutionary history.
 Other factors may have played an important role, particularly in the evolution of genes
and proteins.
 By attributing the diversity of life to natural causes, Darwin gave biology a sound
scientific basis.
 As Darwin said, “There is grandeur in this view of life.”

Biology Chapter Notes

Chapter 23 The Evolution of Populations
Chapter Notes

Overview: The Smallest Unit of Evolution

 One common misconception about evolution is that organisms evolve, in a Darwinian

sense, during their lifetimes.
 Natural selection does act on individuals. Each individual’s combination of inherited
traits affects its survival and its reproductive success relative to other individuals in the
 However, the evolutionary impact of natural selection is only apparent in the changes
in a population of organisms over time.
 It is the population, not the individual, that evolves.
 Consider the example of bent grass (Agrostis tenuis) growing on the tailings of an
abandoned mine. These tailings are rich in toxic heavy metals.
 While many bent grass seeds land on the mine tailings each year, the only plants that
germinate, grow, and reproduce are those that possess genes enabling them to tolerate
metallic soils.
 These plants tend to produce metal-tolerant offspring.
 Individual plants do not evolve to become more metal-tolerant during their lifetimes.
Concept 23.1 Population genetics provides a foundation for studying evolution
 Darwin proposed a mechanism for change in species over time.
 What was missing from Darwin’s explanation was an understanding of inheritance that
could explain how chance variations arise in a population while also accounting for the
precise transmission of these variations from parents to offspring.
 The widely accepted hypothesis of the time—that the traits of parents are blended in
their offspring—would eliminate the differences in individuals over time.
 Just a few years after Darwin published On the Origin of Species, Gregor Mendel
proposed a model of inheritance that supported Darwin’s theory.
 Mendel’s particulate hypothesis of inheritance stated that parents pass on discrete
heritable units (genes) that retain their identities in offspring.
 Although Gregor Mendel and Charles Darwin were contemporaries, Darwin never saw
Mendel’s paper, and its implications were not understood by the few scientists who did
read it at the time.
 Mendel’s contribution to evolutionary theory was not appreciated until half a century
The modern evolutionary synthesis integrated Darwinian selection and Mendelian
 When Mendel’s research was rediscovered in the early 20th century, many geneticists
believed that his laws of inheritance conflicted with Darwin’s theory of natural selection.
 Darwin emphasized quantitative characters, those that vary along a continuum.
 These characters are influenced by multiple loci.
 Mendel and later geneticists investigated discrete “either-or” traits.
 It was not obvious that there was a genetic basis to quantitative characters.
Biology Chapter Notes
 Within a few decades, geneticists determined that quantitative characters are influenced
by multiple genetic loci and that the alleles at each locus follow Mendelian laws of
 These discoveries helped reconcile Darwin’s and Mendel’s ideas and led to the birth of
population genetics, the study of how populations change genetically over time.
 A comprehensive theory of evolution, the modern synthesis, took form in the early
 It integrated discoveries and ideas from paleontology, taxonomy, biogeography, and
population genetics.
 The first architects of the modern synthesis included statistician R. A. Fisher, who
demonstrated the rules by which Mendelian characters are inherited, and biologist J. B. S.
Haldane, who explored the rules of natural selection. Later contributors included
geneticists Theodosius Dobzhansky and Sewall Wright, biogeographer and taxonomist
Ernst Mayr, paleontologist George Gaylord Simpson, and botanist G. Ledyard Stebbins.
 The modern synthesis emphasizes:
 The importance of populations as the units of evolution.
 The central role of natural selection as the most important mechanism of adaptive
 The idea of gradualism to explain how large changes can evolve as an accumulation of
small changes over long periods of time.
 While many evolutionary biologists are now challenging some of the assumptions of the
modern synthesis, it has shaped our ideas about how populations evolve.
A population’s gene pool is defined by its allele frequencies.
 A population is a localized group of individuals that belong to the same species.
 One definition of a species is a group of natural populations whose individuals have the
potential to interbreed and produce fertile offspring.
 Populations of a species may be isolated from each other and rarely exchange genetic
 Members of a population are far more likely to breed with members of the same
population than with members of other populations.
 Individuals near the population’s center are, on average, more closely related to one
another than to members of other populations.
 The total aggregate of genes in a population at any one time is called the population’s
gene pool.
 It consists of all alleles at all gene loci in all individuals of a population.
 If only one allele exists at a particular locus in a population, that allele is said to be
fixed in the gene pool, and all individuals will be homozygous for that gene.
 If there are two or more alleles for a particular locus, then individuals can be either
homozygous or heterozygous for that gene.
 Each allele has a frequency in the population’s gene pool.
 For example, imagine a population of 500 wildflower plants with two alleles (C R and CW)
at a locus that codes for flower pigment.
 Suppose that in the imaginary population of 500 plants, 20 (4%) are homozygous for
the CW allele (CWCW) and have white flowers.

Biology Chapter Notes

 Of the remaining plants, 320 (64%) are homozygous for the C R allele (CRCR) and have
red flowers.
 These alleles show incomplete dominance. 160 (32%) of the plants are heterozygous
(CRCW) and produce pink flowers.
 Because these plants are diploid, the population of 500 plants has 1,000 copies of the gene
for flower color.
 The R W
dominant allele (CR) accounts for 800 copies (320 × 2 for CRCR + 160 × 1 for
C C ).
 The frequency of the CR allele in the gene pool of this population is 800/1,000 = 0.8, or
 The CW allele must have a frequency of 1.0 − 0.8 = 0.2, or 20%.
 When there are two alleles at a locus, the convention is to use p to represent the frequency
of one allele and q to represent the frequency of the other.
 Thus p, the frequency of the CR allele in this population, is 0.8.
 The frequency of the CW allele, represented by q, is 0.2.
The Hardy-Weinberg Theorem describes a nonevolving population.
 The Hardy-Weinberg theorem describes the gene pool of a nonevolving population.
 This theorem states that the frequencies of alleles and genotypes in a population’s gene
pool will remain constant over generations unless acted upon by agents other than
Mendelian segregation and recombination of alleles.
 The shuffling of alleles by meiosis and random fertilization has no effect on the overall
gene pool of a population.
 In our imaginary wildflower population of 500 plants, 80% (0.8) of the flower color
alleles are CR, and 20% (0.2) are CW.
 How will meiosis and sexual reproduction affect the frequencies of the two alleles in the
next generation?
 We assume that fertilization is completely random and all male-female mating
combinations are equally likely.
 Because each gamete has only one allele for flower color, we expect that a gamete drawn
from the geneW pool at random has a 0.8 chance of bearing an C R allele and a 0.2 chance of
bearing an C allele.
 Suppose that the individuals in a population not only donate gametes to the next
generation at random, but also mate at random. In other words, all male-female matings
are equally likely.
 The allele frequencies in this population will not change from one generation to the
next. Its genotype frequencies, which can be predicted from the allele frequencies, will
also remain unchanged.
 For the flower-color locus, the population’s genetic structure is in a state of Hardy-
Weinberg equilibrium.
 Using the rule of multiplication, we can determine the frequencies of the three possible
genotypes in the next generation.
 The probability of picking two CR alleles (to obtain a CRCR genotype) is 0.8 × 0.8 =
0.64, or 64%.
 The probability of picking two CW alleles (to obtain a CWCW genotype) is 0.2 × 0.2 =
0.04, or 4%.

Biology Chapter Notes

 Heterozygous individuals are either C RCW or CWCR, depending on whether the CR
allele arrived via sperm or egg.
 The probability of being heterozygous (with a C RCW genotype) is 0.8 ×R0.2 = 0.16 for
C C , 0.2 × 0.8 = 0.16 for C C , and 0.16 + 0.16 = 0.32, or 32%, for C CW + CWCR.

 As you can see, the processes of meiosis and random fertilization have maintained the
same allele and genotype frequencies that existed in the previous generation.
 The Hardy-Weinberg theorem states that the repeated shuffling of a population’s gene
pool over generations does not increase the frequency of one allele over another.
 Theoretically, the allele frequencies in our flower population should remain at 0.8 for
CR and 0.2 for CW forever.
 To generalize the example, in a population with two alleles with frequencies of p and q,
the combined frequencies must add to 100%.
 Therefore p + q = 1.
 If p + q = 1, then p = 1 − q and q = 1 − p.
 In the wildflower W
example, p is the frequency of red alleles (CR) and q is the frequency of
white alleles (C ).
 The probability of generating an CRCR offspring is p2 (an application of the rule of
 In our example, p = 0.8 and p2 = 0.64.
 The probability of generating a CWCW offspring is q2.
 In our example, q = 0.2 and q2 = 0.04.
 The probability of generating a CRCW offspring is 2pq.
 In our example, 2 × 0.8 × 0.2 = 0.32.
 The genotype frequencies must add up to 1.0:
 p2 + 2pq + q2 = 1.0
 For the wildflowers, 0.64 + 0.32 + 0.04 = 1.0.
 This general formula is the Hardy-Weinberg equation.
 Using this formula, we can calculate frequencies of alleles in a gene pool if we know the
frequency of genotypes, or the frequency of genotypes if we know the frequencies of
Five conditions must be met for a population to remain in Hardy-Weinberg equilibrium.
 The Hardy-Weinberg theorem describes a hypothetic population that is not evolving.
However, real populations do evolve, and their allele and genotype frequencies do change
over time.
 That is because the five conditions for nonevolving populations are rarely met for long in
 A population must satisfy five conditions if it is to remain in Hardy-Weinberg
o Extremely large population size. In small populations, chance fluctuations in the gene
pool can cause genotype frequencies to change over time. These random changes are
called genetic drift.
o No gene flow. Gene flow, the transfer of alleles due to the migration of individuals or
gametes between populations, can change the proportions of alleles.
o No mutations. Introduction, loss, or modification of genes will alter the gene pool.
Biology Chapter Notes
o Random mating. If individuals pick mates with certain genotypes, or if inbreeding is
common, the mixing of gametes will not be random.
o No natural selection. Differential survival or reproductive success among genotypes
will alter their frequencies.
 Evolution usually results when any of these five conditions are not met.
 Although natural populations are rarely, if ever, in true Hardy-Weinberg equilibrium, the
rate of evolutionary change in many populations is so slow that they appear to be close to
 In such cases, we can use the Hardy-Weinberg equation to estimate genotype and
allele frequencies.
 We can use the theorem to estimate the percentage of the human population that carries
the allele for the inherited disease phenylketonuria (PKU).
 About 1 in 10,000 babies born in the United States is born with PKU, a metabolic
condition that results in mental retardation and other problems if left untreated.
 The disease is caused by a recessive allele.
 Is the U.S. population in Hardy-Weinberg equilibrium with respect to the PKU gene?
o The U.S. population is very large.
o Populations outside the United States have PKU allele frequencies similar to those
seen in the United States, so gene flow will not alter allele frequencies significantly.
o The mutation rate for the PKU gene is very low.
o People do not choose their partners based on whether or not they carry the PKU allele,
and inbreeding (marriage to close relatives) is rare in the United States.
o Selection against PKU only acts against the rare heterozygous recessive individuals.
 From the epidemiological data, we know that frequency of homozygous recessive
individuals (q2 in the Hardy-Weinberg theorem) = 1 in 10,000, or 0.0001.
 The frequency of the recessive allele (q) is the square root of 0.0001 = 0.01.
 The frequency of the dominant allele (p) is p = 1 − q, or 1 − 0.01 = 0.99.
 The frequency of carriers (heterozygous individuals) is 2pq = 2 × 0.99 × 0.01 =
0.0198, or about 2%.
 Thus, about 2% of the U.S. population carries the PKU allele.

Concept 23.2 Mutation and sexual recombination produce the variation that makes
evolution possible
New genes and new alleles originate only by mutation.
 A mutation is a change in the nucleotide sequence of an organism’s DNA.
 Most mutations occur in somatic cells and are lost when the individual dies.
 Only mutations in cell lines that form gametes can be passed on to offspring, and only a
small fraction of these spread through populations and become fixed.
 A new mutation that is transmitted in a gamete to an offspring can immediately change
the gene pool of a population by introducing a new allele.
 A point mutation is a change of a single base in a gene.
Biology Chapter Notes
 Point mutations can have a significant impact on phenotype, as in the case of sickle-cell
 However, most point mutations are harmless.
 Much of the DNA in eukaryotic genomes does not code for protein products.
 However, some noncoding regions of DNA do regulate gene expression.
 Changes in these regulatory regions of DNA can have profound effects.
 Because the genetic code is redundant, some point mutations in genes that code for
proteins may not alter the protein’s amino acid composition.
 On rare occasions, a mutant allele may actually make its bearer better suited to the
environment, increasing reproductive success.
 This is more likely when the environment is changing.
 Some mutations alter gene number or sequence.
 Chromosomal mutations that delete or rearrange many gene loci at once are almost
always harmful.
 In rare cases, chromosomal rearrangements may be beneficial.
 For example, the translocation of part of one chromosome to a different
chromosome could link genes that act together to positive effect.
 Gene duplication is an important source of new genetic variation.
 Small pieces of DNA can be introduced into the genome through the activity of
 Such duplicated segments can persist over generations and provide new loci that may
eventually take on new functions by mutation and subsequent selection.
 New genes may also arise when the coding subsections of genes known as exons are
shuffled within the genome, within a single locus or between loci.
 Such beneficial increases in gene number appear to have played a major role in evolution.
 For example, mammalian ancestors carried a single gene for detecting odors that has been
duplicated though various mutational mechanisms.
 Modern humans have close to 1,000 olfactory receptor genes.
 60% of these genes have been inactivated in humans, due to mutations.
 Mice, who rely more on their sense of smell, have lost only 20% of their olfactory
receptor genes.
 Mutation rates vary from organism to organism.
 Mutation rates are low in animals and plants, averaging about 1 mutation in every
100,000 genes per generation.
 In microorganisms and viruses with short generation spans, mutation rates are much
higher and can rapidly generate genetic variation.
Sexual recombination also produces genetic variation.
 On a generation-to-generation timescale, sexual recombination is far more important than
mutation in producing the genetic differences that make adaptation possible.
 Sexual reproduction rearranges alleles into novel combinations every generation.
 Bacteria and viruses can also undergo recombination, but they do so less regularly than
animals and plants.
 Bacterial and viral recombination may cross species barriers.

Biology Chapter Notes

Concept 23.3 Natural selection, genetic drift, and gene flow can alter a population’s
genetic composition
 Although new mutations can modify allele frequencies, the change from generation to
generation is very small.
 Recombination reshuffles alleles but does not change their frequency.
 Three major factors alter allele frequencies to bring about evolutionary change: natural
selection, genetic drift, and gene flow.
Natural selection is based on differential reproductive success.
 Individuals in a population vary in their heritable traits.
 Those with variations better suited to the environment tend to produce more offspring
than those with variations that are less well suited.
 As a result of selection, alleles are passed on to the next generation in frequencies
different from their relative frequencies in the present population.
 Imagine that in our imaginary wildflower population, white flowers are more visible to
herbivorous insects and thus have lower survival. Imagine that red flowers are more
visible to pollinators.
 Such differences in survival and reproductive W
success would disturb the Hardy-
Weinberg equilibrium. The frequency of the C allele would decline and the frequency
of the CR allele would increase.
Genetic drift results from chance fluctuations in allele frequencies in small populations.
 Genetic drift occurs when changes in gene frequencies from one generation to another
occur because of chance events (sampling errors) that occur in small populations.
 For example, you would not be too surprised if a thrown coin produced seven heads
and three tails in ten tosses, but you would be surprised if you saw 700 heads and 300
tails in 1,000 tosses—you would expect close to 500 of each.
 The smaller the sample, the greater the chance of deviation from the expected result.
 In a large population, allele frequencies will not change from generation to generation by
chance alone.
 However, in a small wildflower population with a stable size of only ten plants, genetic
drift can completely eliminate some alleles.
 Genetic drift at small population sizes may occur as a result of two situations: the
bottleneck effect or the founder effect.
 The bottleneck effect occurs when the numbers of individuals in a large population are
drastically reduced by a disaster.
 By chance, some alleles may be overrepresented and others underrepresented among
the survivors.
 Some alleles may be eliminated altogether.
 Genetic drift will continue to change the gene pool until the population is large enough
to eliminate the effect of chance fluctuations.
 The bottleneck effect is an important concept in conservation biology of endangered
 Populations that have suffered bottleneck incidents have lost genetic variation from the
gene pool.
Biology Chapter Notes
 This reduces individual variation and may reduce adaptation.
 For example, in the 1890s, hunters reduced the population of northern elephant
seals in California to 20 individuals.
 Now that it is a protected species, the population has increased to more than 30,000.
 However, a study of 24 gene loci in a representative sample of seals showed no
variation. One allele had been fixed for each gene.
 Populations of the closely related southern elephant seal, which did not go through
a bottleneck, show abundant genetic variation.
 The founder effect occurs when a new population is started by only a few individuals
who do not represent the gene pool of the larger source population.
 At an extreme, a population could be started by a single pregnant female or single seed
with only a tiny fraction of the genetic variation of the source population.
 Genetic drift would continue from generation to generation until the population grew
large enough for sampling errors to be minimal.
 Founder effects have been demonstrated in human populations that started from a
small group of colonists.
A population may lose or gain alleles by gene flow.
 Gene flow is genetic exchange due to migration of fertile individuals or gametes between
 For example, if a nearby wildflower population consisted entirely of white flowers, its
pollen (CW alleles only) could be carried into our target population.
 This would increase the frequency of CW alleles in the target population in the next
 Gene flow tends to reduce differences between populations.
 If extensive enough, gene flow can amalgamate neighboring populations into a single
population with a common gene pool.
 Humans today migrate much more freely than in the past, and gene flow has become
an important agent of evolutionary change in human populations that were previously

Concept 23.4 Natural selection is the primary mechanism of adaptive evolution

 Of all the factors that can change a gene pool, only natural selection leads to adaptation of
an organism to its environment.
 Natural selection accumulates and maintains favorable genotypes in a population.
 Most populations have extensive genetic variation.
 Not all variation is heritable. For example, body builders alter their phenotypes but do not
pass on their huge muscles to their children.
 Only the genetic component of variation can have evolutionary consequences as a result
of natural selection.
 This is because only heritable traits pass from generation to generation.
Genetic variation occurs within and between populations.
 Both quantitative and discrete characters contribute to variation within a population.
 Quantitative characters are those that vary along a continuum within a population.
Biology Chapter Notes
 For example, plant height in a wildflower population ranges from short to tall.
 Quantitative variation is usually due to polygenic inheritance in which the additive
effects of two or more genes influence a single phenotypic character.
 Discrete characters, such as flower color, are usually determined by a single locus with
different alleles that produce distinct phenotypes.
 Phenotypic polymorphism occurs when two or more discrete phenotypes are represented
in high enough frequencies to be noticeable in a population.
 The contrasting forms are called morphs, as in the red-flowered and white-flowered
morphs in our wildflower population.
 Human populations are polymorphic for a variety of physical (e.g., freckles) and
biochemical (e.g., blood types) characters.
 Polymorphism applies only to discrete characters, not quantitative characters.
 Human height, which varies in a continuum, is not a phenotypic polymorphism.
 Population geneticists measure genetic variation by determining the amount of
heterozygosity at the level of whole genes (gene variability) and at the molecular level of
DNA (nucleotide variability).
 Average heterozygosity measures gene variability, the average percent of gene loci that
are heterozygous.
 In the fruit fly (Drosophila), about 86% of their 13,000 gene loci are homozygous
 About 14% (1,800 genes) are heterozygous.
 Nucleotide variability measures the mean level of difference in nucleotide sequences
(base pair differences) among individuals in a population.
 In fruit flies, about 1% of the bases differ between two individuals.
 Two individuals differ, on average, at 1.8 million of the 180 million nucleotides in the
fruit fly genome.
 Why does average heterozygosity tend to be greater than nucleotide diversity?
 This is because a gene can consist of thousands of bases of DNA. A difference at only
one of these bases is sufficient to make two alleles of that gene different and count
toward average heterozygosity.
 Humans have relatively little genetic variation.
 Nucleotide diversity is only 0.1%.
 You and your neighbor probably have the same nucleotide at 999 out of every 1,000
nucleotide sites in your DNA.
 Geographic variation results from differences in phenotypes or genotypes between
populations or between subgroups of a single population that inhabit different areas.
 Natural selection contributes to geographic variation by modifying gene frequencies in
response to differences in local environmental factors.
 Genetic drift can also lead to variation among populations through the cumulative
effect of random fluctuations in allele frequencies.
 Geographic variation can occur on a local scale, within a population, if the environment is
patchy or if dispersal of individuals is limited, producing subpopulations. This is termed
spatial variation.
 Geographic variation in the form of graded change in a trait along a geographic axis is
called a cline.

Biology Chapter Notes

 Clines may represent intergrade zones where individuals from neighboring, genetically
different, populations interbreed.
 Alternatively, clines may reflect the influence of natural selection based on gradation
in some environmental variable.
 For example, the average body size of many North American species of birds and
mammals increases gradually with increasing latitude, allowing Northern
populations to conserve heat in cold environments by decreasing the ratio of surface
area to volume.
Let’s take a closer look at natural selection.
 The terms “struggle for existence” and “survival of the fittest” are misleading because
they suggest that individuals compete directly in contests.
 In some animal species, males do compete directly for mates.
 Reproductive success is generally subtler and depends on factors other than battle for
 For example, a barnacle may produce more eggs than its neighbors because it is more
efficient at filtering food from the water.
 Wildflowers may be successful because they attract more pollinators.
 These examples of adaptive advantage are all components of evolutionary fitness.
 Fitness is defined as the contribution an individual makes to the gene pool of the next
generation, relative to the contributions of other individuals.
 Population geneticists define relative fitness as the contribution of a genotype to the next
generation compared to the contribution of alternative genotypes for the same locus.
 Consider our wildflower population.
 Let’s assume that individuals with red flowers produce fewer offspring than those with
white or pink flowers, which produce equal numbers of offspring.
 The relative fitness of the most successfulWvariants is set at 1.0 as a basis for
comparison, so the relative fitness of white (C CW) and pink (CRCW) plants is 1.0.
 If plants with red flowers (CRCR) produce only 80% as many offspring, their relative
fitness is 0.8.
 Although population geneticists measure the relative fitness of a genotype, it is important
to remember that natural selection acts on phenotypes, not genotypes.
 The whole organism is subjected to natural selection.
 The relative fitness of an allele depends on the entire genetic and environmental context in
which it is expressed.
 Survival alone does not guarantee reproductive success.
 Relative fitness is zero for a sterile organism, even if it is robust and long-lived.
 On the other hand, longevity may increase fitness if long-lived individuals leave more
offspring than short-lived individuals.
 In many species, individuals that mature quickly, become fertile at an early age, and live
for a short time have greater relative fitness than individuals that live longer but mature
There are three modes of selection: directional, disruptive, and stabilizing.
 Natural selection can alter the frequency distribution of heritable traits in three ways,
depending on which phenotypes in a population are favored.
Biology Chapter Notes
 The three modes of selection are called directional, disruptive, and stabilizing selection.
 Directional selection is most common during periods of environmental change or when
members of a population migrate to a new habitat with different environmental
 Directional selection shifts the frequency curve for a phenotypic character in one direction
by favoring individuals who deviate from the average.
 For example, fossil evidence indicates that the average size of black bears in Europe
increased during each glacial period, only to decrease again during the warmer interglacial
 Large bears have a smaller surface-to-volume ratio and are better at conserving body
heat during periods of extreme cold.
 Disruptive selection occurs when environmental conditions favor individuals at both
extremes of the phenotypic range over those with intermediate phenotypes.
 For example, two distinct bill types are present in Cameroon’s black-bellied
seedcrackers. Larger-billed birds are more efficient in feeding on hard seeds and
smaller-billed birds are more efficient in feeding on soft seeds.
 Birds with intermediate bills are relatively inefficient at cracking both types of seeds
and thus have lower relative fitness.
 Disruptive selection can be important in the early stages of speciation.
 Stabilizing selection favors intermediate variants and acts against extreme phenotypes.
 Stabilizing selection reduces variation and maintains the status quo for a trait.
 Human birth weight is subject to stabilizing selection.
 Babies much larger or smaller than 3–4 kg have higher infant mortality than average-
sized babies.
Diploidy and balancing selection preserve genetic variation.
 The tendency for natural selection to reduce variation is countered by mechanisms that
preserve or restore variation, including diploidy and balanced polymorphisms.
 Diploidy in eukaryotes prevents the elimination of recessive alleles via selection because
recessive alleles do not affect the phenotype in heterozygotes.
 Even recessive alleles that are unfavorable can persist in a population through their
propagation by heterozygous individuals.
 Recessive alleles are only exposed to selection when both parents carry the same recessive
allele and combine two recessive alleles in one zygote.
 This happens only rarely when the frequency of the recessive allele is very low.
 The rarer the recessive allele, the greater the degree of protection it has from natural
 Heterozygote protection maintains a huge pool of alleles that may not be suitable under
the present conditions but may become beneficial when the environment changes.
 Natural selection itself preserves variation at some gene loci.
 Balancing selection occurs when natural selection maintains stable frequencies of two or
more phenotypes in a population, a state called balanced polymorphism.
 One mechanism producing balanced polymorphism is heterozygote advantage.
 In some situations, individuals who are heterozygous at a particular locus have greater
fitness than homozygotes.
Biology Chapter Notes
 In these cases, natural selection will maintain multiple alleles at that locus.
 Heterozygous advantage maintains genetic diversity at the human gene for one chain of
 Homozygous recessive individuals suffer from sickle-cell disease.
 Homozygous dominant individuals are vulnerable to malaria.
 Heterozygous individuals are resistant to malaria.
 The frequency of the sickle-cell allele is highest in areas where the malarial parasite is
 In some African tribes, it accounts for 20% of the gene pool, a very high frequency for
such a harmful allele.
 Even at this high frequency, only 4% of the population suffers from sickle-cell disease
(q2 = 0.2 × 0.2 = 0.04), while 32% of the population is resistant to malaria (2pq = 2 ×
0.8 × 0.2 = 0.32).
 The aggregate benefit of the sickle-cell allele in the population balances its aggregate
 A second mechanism promoting balanced polymorphism is frequency-dependent
 Frequency-dependent selection occurs when the fitness of any one morph declines if it
becomes too common in the population.
 Predators may develop “search images” of the most common forms of prey. A prey
morph that becomes too common may become disproportionately vulnerable to
 Frequency-dependent selection has been observed in a number of predator-prey
interactions in the wild.
 Some genetic variations, neutral variations, have negligible impact on fitness, and thus
natural selection does not affect these alleles.
 For example, the diversity of human fingerprints seems to confer no selective
advantage to some individuals over others.
 Most of the base differences between humans that are found in untranslated parts of
the genome appear to confer no selective advantage.
 Pseudogenes, genes that have become inactivated by mutations, accumulate genetic
 Over time, some neutral alleles will increase and others will decrease by the chance
effects of genetic drift.
 There is no consensus among biologists on how much genetic variation can be classified
as neutral or even if any variation can be considered truly neutral.
 It is almost impossible to demonstrate that an allele brings no benefit at all to an
 Also, variant alleles may be neutral in one environment but not in another.
 Even if only a fraction of the extensive variation in a gene pool significantly affects an
organism, there is still an enormous reservoir of raw material for natural selection and
adaptive evolution.
Sexual selection may lead to pronounced secondary differences between the sexes.
 Charles Darwin was the first scientist to investigate sexual selection, which is natural
selection for mating success.

Biology Chapter Notes

 Sexual selection results in sexual dimorphism, marked differences between the sexes in
secondary sexual characteristics not directly associated with reproduction.
 Males and females may differ in size, coloration, and ornamentation.
 In vertebrates, males are usually the larger and showier sex.
 It is important to distinguish between intrasexual and intersexual selection.
 Intrasexual selection is direct competition among individuals of one sex (usually males)
for mates of the opposite sex.
 Competition may take the form of direct physical battles between individuals.
 The stronger individuals gain status.
 More commonly, ritualized displays discourage lesser competitors and determine
 Evidence is growing that intrasexual selection can take place between females as well.
 Intersexual selection or mate choice occurs when members of one sex (usually females)
are choosy in selecting their mates from individuals of the other sex.
 Because females invest more in eggs and parental care, they are choosier about their
mates than males.
 A female tries to select a mate that will confer a fitness advantage on their mutual
 In many cases, the female chooses a male based on his showy appearance or behavior.
 Some male showiness does not seem to be adaptive except in attracting mates and may
put the male at considerable risk.
 For example, bright plumage may make male birds more visible to predators.
 Even if these extravagant features have some costs, individuals that possess them
will have enhanced fitness if they help an individual gain a mate.
 Every time a female chooses a mate based on appearance or behavior, she
perpetuates the alleles that caused her to make that choice.
 She also allows a male with that particular phenotype to perpetuate his alleles.
 How do female preferences for certain male characteristics evolve? Are there fitness
benefits to showy traits?
 Several researchers are testing the hypothesis that females use male sexual
advertisements to measure the male’s overall health.
 Males with serious parasitic infections may have dull, disheveled plumage.
 These individuals are unlikely to win many females.
 If a female chooses a showy mate, she may be choosing a healthy one, and her benefit
is a greater probability of having healthy offspring.
Sex is an evolutionary enigma.
 As a mechanism of rapid population growth, sex is far inferior to asexual reproduction.
 Consider a population in which half the females reproduce only asexually and half the
females reproduce only sexually.
 Assume that both types of females produce equal numbers of offspring each
 The asexual condition will increase in frequency, because:
 All offspring of asexual females will be reproductive daughters.
 Only half of the offspring of sexual females will be daughters; the other half will
necessarily be males.
Biology Chapter Notes
 Sex is maintained in the vast majority of eukaryotic species, even those that also
reproduce asexually.
 Sex must confer some selective advantage to compensate for the costs of diminished
reproductive output.
 Otherwise, migration of asexual individuals or mutation permitting asexual
reproduction would outcompete sexual individuals and the alleles favoring sex.
 The traditional explanation for the maintenance of sex was that the process of meiosis and
fertilization generate genetic variation on which natural selection can act.
 However, the assumption that sex is maintained in spite of its disadvantages because it
produces future adaptation in a variable world is difficult to defend.
 Natural selection acts in the present, favoring individuals here and now that best fit the
current, local environment.
 Let us instead consider how the genetic variation promoted by sex might be advantageous
in the short term, on a generation-to-generation timescale.
 Genetic variability may be important in resistance to disease.
 Parasites and pathogens recognize and infect their hosts by attaching to receptor
molecules on the host’s cells.
 There should be an advantage to producing offspring that vary in their resistance to
different diseases.
 One offspring may have cellular markers that make it resistant to virus A, while
another is resistant to virus B.
 This hypothesis predicts that gene loci that code for receptors to which pathogens
attack should have many alleles.
 In humans, there are hundreds of alleles for each of two gene loci that give cell
surfaces their molecular fingerprints.
 At the same time, parasites evolve very rapidly in their ability to use specific host
 However, sex provides a mechanism for changing the distribution of alleles and
varying them among offspring.
 This coevolution in which host and parasite must evolve quickly to keep up with each
other has been called a “Red Queen race.”
Natural selection cannot fashion perfect organisms.
 There are at least four reasons natural selection cannot produce perfection.
o Evolution is limited by historical constraints.
 Evolution does not scrap ancestral features and build new complex structures or
behavior from scratch.
 Evolution co-opts existing features and adapts them to new situations.
 For example, birds might benefit from having wings plus four legs. However, birds
descended from reptiles that had only two pairs of limbs. Co-opting the forelimbs for
flight left only two hind limbs for movement on the ground.
o Adaptations are often compromises.
 Each organism must do many different things.
 Because the flippers of a seal must allow it to walk on land and also swim efficiently,
their design is a compromise between these environments.
 Similarly, human limbs are flexible and allow versatile movements, but are prone to
injuries, such as sprains, torn ligaments, and dislocations.
Biology Chapter Notes
 Better structural reinforcement would compromise agility.
o Chance and natural selection interact.
 Chance events affect the subsequent evolutionary history of populations.
 For example, founders of new populations may not necessarily be the individuals best
suited to the new environment, but rather those individuals that were carried there by
o Selection can only edit existing variations.
 Natural selection favors only the fittest variations from those phenotypes that are
 New alleles do not arise on demand.
 Natural selection works by favoring the best variants available.
 The many imperfections of living organisms are evidence for evolution.

Biology Chapter Notes

Chapter 24 The Origin of Species
Chapter Notes

Overview: That “Mystery of Mysteries”

 Darwin visited the Galápagos Islands and found them filled with plants and animals
that lived nowhere else in the world.
 He realized that he was observing newly emerged species on these young islands.
 Speciation—the origin of new species—is at the focal point of evolutionary theory
because the appearance of new species is the source of biological diversity.
 Microevolution is the study of adaptive change in a population.
 Macroevolution addresses evolutionary changes above the species level.
 It deals with questions such as the appearance of evolutionary novelties (e.g.,
feathers and flight in birds) that can be used to define higher taxa.
 Speciation addresses the question of how new species originate and develop through
the subdivision and subsequent divergence of gene pools.
 The fossil record chronicles two patterns of speciation: anagenesis and cladogenesis.
 Anagenesis, phyletic evolution, is the accumulation of changes associated with the
gradual transformation of one species into another.
 Cladogenesis, branching evolution, is the budding of one or more new species from a
parent species.
 Only cladogenesis promotes biological diversity by increasing the number of

 Concept 24.1 The biological species concept emphasizes reproductive isolation
 Species is a Latin word meaning “kind” or “appearance.”
 Traditionally, morphological differences have been used to distinguish species.
 Today, differences in body function, biochemistry, behavior, and genetic makeup
are also used to differentiate species.
 Are organisms truly divided into the discrete units we called species, or is this
classification an arbitrary attempt to impose order on the natural world?
 In 1942, Ernst Mayr proposed the biological species concept.

Biology Chapter Notes

 A species is defined as a population or group of populations whose members have
the potential to breed with each other in nature to produce viable, fertile
offspring, but who cannot produce viable, fertile offspring with members of other
 A biological species is the largest set of populations in which genetic exchange is
possible and that is genetically isolated from other populations.
 Species are based on interfertility, not physical similarity.
 For example, eastern and western meadowlarks have similar shapes and coloration,
but differences in song help prevent interbreeding between the two species.
 In contrast, humans have considerable diversity, but we all belong to the same
species because of our capacity to interbreed.
 Prezygotic and postzygotic barriers isolate the gene pools of biological species.
 Because the distinction between biological species depends on reproductive
incompatibility, the concept hinges on reproductive isolation, the existence of
biological barriers that prevent members of two species from producing viable,
fertile hybrids.
 A single barrier may not block all genetic exchange between species, but a
combination of several barriers can effectively isolate a species’ gene pool.
 Typically, these barriers are intrinsic to the organisms, not due to simple
geographic separation.
 Reproductive isolation prevents populations belonging to different species from
interbreeding, even if their ranges overlap.
 Reproductive barriers can be categorized as prezygotic or postzygotic, depending on
whether they function before or after the formation of zygotes.
 Prezygotic barriers impede mating between species or hinder fertilization of ova if
members of different species attempt to mate.
 These barriers include habitat isolation, behavioral isolation, temporal isolation,
mechanical isolation, and gametic isolation.
 Habitat isolation. Two organisms that use different habitats (even in the same
geographic area) are unlikely to encounter each other to even attempt mating.
 Two species of garter snakes in the genus Thamnophis occur in the same areas.
Because one lives mainly in water and the other is primarily terrestrial, they
rarely encounter each other.

Biology Chapter Notes

 Behavioral isolation. Many species use elaborate courtship behaviors unique to the
species to attract mates.
 In many species, elaborate courtship displays identify potential mates of the
correct species and synchronize gonadal maturation.
 In the blue-footed booby, males perform a high-step dance that calls the female’s
attention to the male’s bright blue feet.
 Temporal isolation. Two species that breed during different times of day, different
seasons, or different years cannot mix gametes.
 The geographic ranges of the western spotted skunk and the eastern spotted
skunk overlap. However, they do not interbreed because the former mates in late
summer and the latter in late winter.
 Mechanical isolation. Closely related species may attempt to mate but fail because
they are anatomically incompatible and transfer of sperm is not possible.
 For example, mechanical barriers contribute to the reproductive isolation of
flowering plants that are pollinated by insects or other animals.
 With many insects, the male and female copulatory organs of closely related
species do not fit together, preventing sperm transfer.
 Gametic isolation. The gametes of two species do not form a zygote because of
incompatibilities preventing fertilization.
 In species with internal fertilization, the environment of the female reproductive
tract may not be conducive to the survival of sperm from other species.
 For species with external fertilization, gamete recognition may rely on the
presence of specific molecules on the egg’s coat, which adhere only to specific
molecules on sperm cells of the same species.
 A similar molecular recognition mechanism enables a flower to discriminate
between pollen of the same species and pollen of a different species.
 If a sperm from one species does fertilize the ovum of another, postzygotic barriers
may prevent the hybrid zygote from developing into a viable, fertile adult.
 These barriers include reduced hybrid viability, reduced hybrid fertility, and
hybrid breakdown.
 Reduced hybrid viability. Genetic incompatibility between the two species may abort
the development of the hybrid at some embryonic stage or produce frail offspring.
 This is true for the occasional hybrids between frogs in the genus Rana. Most do
not complete development, and those that do are frail.
Biology Chapter Notes
 Reduced hybrid fertility. Even if the hybrid offspring are vigorous, the hybrids may
be infertile, and the hybrid cannot backbreed with either parental species.
 This infertility may be due to problems in meiosis because of differences in
chromosome number or structure.
 For example, while a mule, the hybrid product of mating between a horse and
donkey, is a robust organism, it cannot mate (except very rarely) with either
horses or donkeys.
 Hybrid breakdown. In some cases, first generation hybrids are viable and fertile.
 However, when they mate with either parent species or with each other, the next
generation is feeble or sterile.
 Strains of cultivated rice have accumulated different mutant recessive alleles at
two loci in the course of their divergence from a common ancestor.
 Hybrids between them are vigorous and fertile, but plants in the next generation
that carry too many of these recessive alleles are small and sterile.
 These strains are in the process of speciating.
 Reproductive barriers can occur before mating, between mating and fertilization, or
after fertilization.
 The biological species concept has some major limitations.
 While the biological species concept has had an important impact on evolutionary
theory, it is limited when applied to species in nature.
 For example, one cannot test the reproductive isolation of morphologically similar
fossils, which are separated into species based on morphology.
 Even for living species, we often lack information on interbreeding needed to
apply the biological species concept.
 In addition, many species (e.g., bacteria) reproduce entirely asexually and are
assigned to species based mainly on structural and biochemical characteristics.
 Many bacteria transfer genes by conjugation and other processes, but this
transfer is different from sexual recombination.
 Evolutionary biologists have proposed several alternative concepts of species.
 Several alternative species concepts emphasize the processes that unite the members
of a species.
 The ecological species concept defines a species in terms of its ecological niche, the set
of environmental resources that a species uses and its role in a biological community.
Biology Chapter Notes
 As an example, a species that is a parasite may be defined in part by its
adaptations to a specific organism.
 This concept accommodates asexual and sexual species.
 The paleontological species concept focuses on morphologically discrete species
known only from the fossil record.
 There is little or no information about the mating capability of fossil species, and
the biological species concept is not useful for them.
 The phylogenetic species concept defines a species as a set of organisms with a unique
genetic history.
 Biologists compare the physical characteristics or molecular sequences of species
to those of other organisms to distinguish groups of individuals that are
sufficiently different to be considered separate species.
 Sibling species are species that appear so similar that they cannot be distinguished
on morphological grounds.
 Scientists apply the biological species concept to determine if the phylogenetic
distinction is confirmed by reproductive incompatibility.
 The morphological species concept, the oldest and still most practical, defines a
species by a unique set of structural features.
 The morphological species concept has certain advantages. It can be applied to
asexual and sexual species, and it can be useful even without information about
the extent of gene flow.
 However, this definition relies on subjective criteria, and researchers sometimes
disagree about which structural features identify a species.
 In practice, scientists use the morphological species concept to distinguish most
 Each species concept may be useful, depending on the situation and the types of
questions we are asking.

 Concept 24.2 Speciation can take place with or without geographic separation
 Two general modes of speciation are distinguished by the way gene flow among
populations is initially interrupted.
 In allopatric speciation, geographic separation of populations restricts gene flow.

Biology Chapter Notes

 In sympatric speciation, speciation occurs in geographically overlapping populations
when biological factors, such as chromosomal changes and nonrandom mating,
reduce gene flow.
 Allopatric speciation: geographic barriers can lead to the origin of species.
 Several geological processes can fragment a population into two or more isolated
 Mountain ranges, glaciers, land bridges, or splintering of lakes may divide one
population into isolated groups.
 Alternatively, some individuals may colonize a new, geographically remote area
and become isolated from the parent population.
 For example, mainland organisms that colonized the Galápagos Islands were
isolated from mainland populations.
 How significant a barrier must be to limit gene exchange depends on the ability of
organisms to move about.
 A geological feature that is only a minor hindrance to one species may be an
impassible barrier to another.
 The valley of the Grand Canyon is a significant barrier for the ground squirrels
that have speciated on opposite sides.
 For birds that can fly across the canyon, it is no barrier.
 Once geographic separation is established, the separated gene pools may begin to
diverge through a number of mechanisms.
 Mutations arise.
 Sexual selection favors different traits in the two populations.
 Different selective pressures in differing environments act on the two populations.
 Genetic drift alters allele frequencies.
 A small, isolated population is more likely to have its gene pool changed substantially
over a short period of time by genetic drift and natural selection.
 For example, less than 2 million years ago, small populations of stray plants and
animals from the South American mainland colonized the Galápagos Islands and
gave rise to the species that now inhabit the islands.
 However, very few small, isolated populations develop into new species; most simply
persist or perish in their new environment.

Biology Chapter Notes

 To confirm that allopatric speciation has occurred, it is necessary to determine
whether the separated populations have become different enough that they can no
longer interbreed and produce fertile offspring when they come back in contact.
 In some cases, researchers bring together members of separated populations in a
laboratory setting.
 Biologists can also assess allopatric speciation in the wild.
 For example, females of the Galápagos ground finch Geospiza difficilis respond
to the songs of males from the same island but ignore the songs of males of the
same species from other islands.
 Sympatric speciation: a new species can originate in the geographic midst of the parent
 In sympatric speciation, new species arise within the range of the parent populations.
 Here reproductive barriers must evolve between sympatric populations.
 In plants, sympatric speciation can result from accidents during cell division that
result in extra sets of chromosomes, a mutant condition known as polyploidy.
 In animals, it may result from gene-based shifts in habitat or mate preference.
 An individual can have more than two sets of chromosomes.
 An autopolyploid mutant is an individual that has more than two chromosome
sets, all derived from a single species.
 For example, a failure of mitosis or meiosis can double a cell’s chromosome
number from diploid (2n) to tetraploid (4n).
 The tetraploid can reproduce with itself (self-pollination) or with other
 It cannot mate with diploids from the original population, because of abnormal
meiosis by the triploid hybrid offspring.
 A more common mechanism of producing polyploid individuals occurs when
allopolyploid offspring are produced by the mating of two different species.
 While the hybrids are usually sterile, they may be quite vigorous and propagate
 In subsequent generations, various mechanisms may transform a sterile hybrid
into a fertile polyploid.
 These polyploid hybrids are fertile with each other but cannot breed with either
parent species.
Biology Chapter Notes
 They thus represent a new biological species.
 The origin of polyploid plant species is common and rapid enough that scientists
have documented several such speciations in historical times.
 For example, two new species of plants called goatsbeard (Tragopodon) appeared
in Idaho and Washington in the early 1900s.
 They are the results of allopolyploidy events between pairs of introduced
European Tragopodon species.
 Many plants important for agriculture are polyploid.
 For example, wheat is an allohexaploid, with six sets of chromosomes from three
different species.
 Oats, cotton, potatoes, and tobacco are polyploid.
 Plant geneticists now use chemicals that induce meiotic and mitotic errors to
create new polyploid plants with special qualities.
 One example is an artificial hybrid combining the high yield of wheat with the
hardiness and disease resistance of rye.
 While polyploid speciation does occur in animals, other mechanisms also contribute
to sympatric speciation in animals.
 Reproductive isolation can result when genetic factors cause individuals to exploit
resources not used by the parent.
 One example is the North American maggot fly, Rhagoletis pomonella.
 The fly’s original habitat was native hawthorn trees.
 About 200 years ago, some populations colonized newly introduced apple trees.
 Because apples mature more quickly than hawthorn fruit, the apple-feeding
flies have been selected for more rapid development and now show temporal
isolation from the hawthorn-feeding maggot flies.
 Speciation is underway.
 Sympatric speciation is one mechanism that has been proposed for the explosive
adaptive radiation of cichlid fishes in Lake Victoria, Africa.
 This vast, shallow lake has filled and dried up repeatedly due to climate changes.
 The current lake is only 12,000 years old but is home to 600 species of cichlid

Biology Chapter Notes

 The species are so genetically similar that many have likely arisen since the
lake last filled.
 While these species are clearly specialized for exploiting different food resources
and other resources, nonrandom mating in which females select males based on a
certain appearance has probably contributed, too.
 Individuals of two closely related sympatric cichlid species will not mate under
normal light because females have specific color preferences and males differ in
 However, under light conditions that de-emphasize color differences, females will
mate with males of the other species and produce viable, fertile offspring.
 It seems likely that the ancestral population was polymorphic for color and that
divergence began with the appearance of two ecological niches that divided the
fish into subpopulations.
 Genetic drift resulted in chance differences in the genetic makeup of the
subpopulations, with different male colors and female preferences.
 Sexual selection reinforced the color differences.
 The lack of postzygotic barriers in this case suggests that speciation occurred
relatively recently.
 As pollution clouds the waters of Lake Victoria, it becomes more difficult for
female cichlids to see differences in male color.
 The gene pools of these two closely related species may blend again.
 We will summarize the differences between sympatric and allopatric speciation.
 In allopatric speciation, a new species forms while geographically isolated from its
parent population.
 As the isolated population accumulates genetic differences due to natural
selection and genetic drift, reproductive isolation from the ancestral species may
arise as a by-product of the genetic change.
 Such reproductive barriers prevent breeding with the parent even if the
populations reestablish contact.
 Sympatric speciation requires the emergence of some reproductive barrier that
isolates a subset of the population without geographic separation from the parent
 In plants, the most common mechanism is hybridization between species or errors
in cell division that lead to polyploid individuals.
Biology Chapter Notes
 In animals, sympatric speciation may occur when a subset of the population is
reproductively isolated by a switch in food source or by sexual selection in a
polymorphic population.
 The evolution of many diversely adapted species from a common ancestor when new
environmental opportunities arise is called adaptive radiation.
 Adaptive radiation occurs when a few organisms make their way into new areas or
when extinction opens up ecological niches for the survivors.
 A major adaptive radiation of mammals followed the extinction of the dinosaurs
65 million years ago.
 The Hawaiian archipelago is a showcase of adaptive radiation.
 Located 3,500 km from the nearest continent, the volcanic islands were formed
“naked” and gradually populated by stray organisms that arrived by wind or
ocean currents.
 The islands are physically diverse, with a range of altitudes and rainfall.
 Multiple invasions and allopatric and sympatric speciation events have ignited an
explosion of adaptive radiation of novel species.
 Researchers study the genetics of speciation.
 Researchers have made great strides in understanding the role of genes in particular
speciation events.
 Douglas Schemske and his colleagues at Michigan State University examined two
species of Mimulus.
 The two species are pollinated by bees and hummingbirds respectively, keeping
their gene pools separate through prezygotic isolation.
 The species show no postzygotic isolation and can be mated readily in the
greenhouse to produce hybrids with flowers that vary in color and shape.
 Researchers observed which pollinators visit which flowers and then investigated
the genetic differences between plants.
 Two gene loci have been identified that are largely responsible for pollinator
 One locus influences flower color; the other affects the amount of nectar flowers
 By determining attractiveness of the flowers to different pollinators, allelic
diversity at these loci has led to speciation.

Biology Chapter Notes

 The tempo of speciation is important.
 In the fossil record, many species appear as new forms rather suddenly (in geologic
terms), persist essentially unchanged, and then disappear from the fossil record.
 Darwin noted this when he remarked that species appeared to undergo modifications
during relatively short periods of their total existence and then remained essentially
 Paleontologists Niles Eldredge and Stephen Jay Gould coined the term punctuated
equilibrium to describe these periods of apparent stasis punctuated by sudden
 Some scientists suggest that these patterns require an explanation outside the
Darwinian model of descent with modification.
 However, this is not necessarily the case.
 Suppose that a species survived for 5 million years, but most of its morphological
alterations occurred in the first 50,000 years of its existence—just 1% of its total
 Because time periods this short often cannot be distinguished in fossil strata, the
species would seem to have appeared suddenly and then lingered with little or no
change before becoming extinct.
 Even though the emergence of this species actually took tens of thousands of
years, this period of change left no fossil record.
 Stasis can also be explained.
 All species continue to adapt after they arise, but often by changes that do not
leave a fossil record, such as small biochemical modifications.
 Paleontologists base hypotheses of descent almost entirely on external morphology.
 During periods of apparent equilibrium, changes in behavior, internal anatomy,
and physiology may not leave a fossil record.
 If the environment changes, the stasis will be broken by punctuations that leave
visible traces in the fossil record.
Concept 24.3 Macroevolutionary changes can accumulate through many speciation
 Speciation is at the boundary between microevolution and macroevolution.
 Microevolution is a change over generations in a population’s allele frequencies,
mainly by genetic drift and natural selection.

Biology Chapter Notes

 Speciation occurs when a population’s genetic divergence from its ancestral
population results in reproductive isolation.
 While the changes after any speciation event may be subtle, the cumulative
change over millions of speciation episodes must account for macroevolution, the
scale of changes seen in the fossil record.
 Most evolutionary novelties are modified versions of older structures.
 The Darwinian concept of descent with modification can account for the major
morphological transformations of macroevolution.
 It may be difficult to believe that a complex organ like the human eye could be the
product of gradual evolution, rather than a finished design created specially for
 However, the key is to remember is that a very simple eye can be very useful to an
 The simplest eyes are just clusters of photoreceptors, light-sensitive pigmented cells.
 These simple eyes appear to have had a single evolutionary origin.
 They are now found in a variety of animals, including limpets.
 These simple eyes have no lenses and cannot focus an image, but they do allow the
animal to distinguish light from dark.
 Limpets cling tightly to their rocks when a shadow falls on them, reducing their
risk of predation.
 Complex eyes have evolved several times independently in the animal kingdom.
 Examples of various levels of complexity, from clusters of photoreceptors to
camera-like eyes, can be seen in molluscs.
 The most complex types did not evolve in one quantum leap, but by incremental
adaptation of organs that benefited their owners at each stage.
 Evolutionary novelties can also arise by gradual refinement of existing structures for
new functions.
 Structures that evolve in one context, but become co-opted for another function,
are exaptations.
 It is important to recognize that natural selection can only improve a structure in the
context of its current utility, not in anticipation of the future.
 An example of an exaptation is the changing function of lightweight, honeycombed
bones of birds.
Biology Chapter Notes
 The fossil record indicates that light bones predated flight.
 Therefore, they must have had some function on the ground, perhaps as a light
frame for agile, bipedal dinosaurs.
 Once flight became an advantage, natural selection would have remodeled the
skeleton to better fit their additional function.
 The wing-like forelimbs and feathers that increased the surface area of these
forelimbs were co-opted for flight after functioning in some other capacity, such
as courtship, thermoregulation, or camouflage.
 Genes that control development play a major role in evolution.
 “Evo-devo” is a field of interdisciplinary research that examines how slight genetic
divergences can become magnified into major morphological differences between
 A particular focus is on genes that program development by controlling the rate,
timing, and spatial pattern of changes in form as an organism develops from a zygote
to an adult.
 Heterochrony, an evolutionary change in the rate or timing of developmental events,
has led to many striking evolutionary transformations.
 Allometric growth tracks how proportions of structures change due to different
growth rates during development.
 Change relative rates of growth even slightly, and you can change the adult form
 Different allometric patterns contribute to the contrast of adult skull shapes
between humans and chimpanzees, which both developed from fairly similar fetal
 Heterochrony appears to be responsible for differences in the feet of tree-dwelling
versus ground-dwelling salamanders.
 The feet of the tree-dwellers are adapted for climbing vertically, with shorter
digits and more webbing.
 This modification may have evolved due to mutations in the alleles that control
the timing of foot development.
 Stunted feet may have resulted if regulatory genes switched off foot growth early.
 In this way, a relatively small genetic change can be amplified into substantial
morphological change.

Biology Chapter Notes

 Another form of heterochrony is concerned with the relative timing of reproductive
development and somatic development.
 If the rate of reproductive development accelerates compared to somatic
development, then a sexually mature stage can retain juvenile structures—a process
called paedomorphosis.
 Some species of salamander have the typical external gills and flattened tail of an
aquatic juvenile, but have functioning gonads.
 Macroevolution can also result from changes in genes that control the placement and
spatial organization of body parts.
 For example, genes called homeotic genes determine such basic features as where
a pair of wings and a pair of legs will develop on a bird or how a plant’s flower
parts are arranged.
 The products of one class of homeotic genes, the Hox genes, provide positional
information in an animal embryo.
 This information prompts cells to develop into structures appropriate for a
particular location.
 One major transition in the evolution of vertebrates is the development of the
walking legs of tetrapods from the fins of fishes.
 A fish fin that lacks external skeletal support evolved into a tetrapod limb that
extends skeletal supports (digits) to the tip of the limb.
 This may be the result of changes in the positional information provided by Hox
genes during limb development, determining how far digits and other bones
should extend from the limb.
 Evolution is not goal oriented.
 The fossil record shows apparent evolutionary trends.
 For example, the evolution of the modern horse can be interpreted to have been a
steady series of changes from a small, browsing ancestor (Hyracotherium) with
four toes to modern horses (Equus) with only one toe per foot and teeth modified
for grazing on grasses.
 It is possible to arrange a succession of animals intermediate between Hyracotherium
and modern horses to show trends toward increased size, reduced number of toes,
and modifications of teeth for grazing.
 If we look at all fossil horses, the illusion of coherent, progressive evolution leading
directly to modern horses vanishes.

Biology Chapter Notes

 Equus is the only surviving twig of an evolutionary bush that included several
adaptive radiations among both grazers and browsers.
 Differences among species in survival can also produce a macroevolutionary trend.
 The species selection model developed by Steven Stanley considers species as
analogous to individuals.
 Speciation is their birth, extinction is their death, and new species are their
 In this model, Stanley suggests that just as individual organisms undergo natural
selection, species undergo species selection.
 The species that endure the longest and generate the greatest number of new species
determine the direction of major evolutionary trends.
 The species selection model suggests that “differential speciation success” plays a
role in macroevolution similar to the role of differential reproductive success in
 To the extent that speciation rates and species longevity reflect success, the analogy
to natural selection is even stronger.
 However, qualities unrelated to the overall success of organisms in specific
environments may be equally important in species selection.
 As an example, the ability of a species to disperse to new locations may contribute
to its giving rise to a large number of “daughter species.”
 The appearance of an evolutionary trend does not imply some intrinsic drive toward
a preordained state of being.
 Evolution is a response to interactions between organisms and their current
environments, leading to changes in evolutionary trends as conditions change.

Biology Chapter Notes

Chapter 25 Phylogeny and Systematics
Chapter Notes

Overview: Investigating the Tree of Life

 Evolutionary biology is about both process and history.

 The processes of evolution are natural selection and other mechanisms that change the
genetic composition of populations and can lead to the evolution of new species.
 A major goal of evolutionary biology is to reconstruct the history of life on earth.
 In this chapter, we will consider how scientists trace phylogeny, the evolutionary history
of a group of organisms.
 To reconstruct phylogeny, scientists use systematics, an analytical approach to
understanding the diversity and relationships of living and extinct organisms.
 Evidence used to reconstruct phylogenies can be obtained from the fossil record and
from morphological and biochemical similarities between organisms.
 In recent decades, systematists have gained a powerful new tool in molecular
systematics, which uses comparisons of nucleotide sequences in DNA and RNA to
help identify evolutionary relationships between individual genes or even entire
 Scientists are working to construct a universal tree of life, which will be refined as the
database of DNA and RNA sequences grows.

Concept 25.1 Phylogenies are based on common ancestries inferred from fossil,
morphological, and molecular evidence
Sedimentary rocks are the richest source of fossils.
 Fossils are the preserved remnants or impressions left by organisms that lived in the past.
 In essence, they are the historical documents of biology.
 Sedimentary rocks form from layers of sand and silt that are carried by rivers to seas and
swamps, where the minerals settle to the bottom along with the remains of organisms.
 As deposits pile up, they compress older sediments below them into layers called
 The fossil record is the ordered array in which fossils appear within sedimentary rock
 These rocks record the passing of geological time.
 Fossils can be used to construct phylogenies only if we can determine their ages.
 The fossil record is a substantial, but incomplete, chronicle of evolutionary change.
 The majority of living things were not captured as fossils upon their death.
 Of those that formed fossils, later geological processes destroyed many.
 Only a fraction of existing fossils have been discovered.
 The fossil record is biased in favor of species that existed for a long time, were
abundant and widespread, and had hard shells or skeletons that fossilized readily.
Morphological and molecular similarities may provide clues to phylogeny.
Biology Chapter Notes
 Similarities due to shared ancestry are called homologies.
 Organisms that share similar morphologies or DNA sequences are likely to be more
closely related than organisms without such similarities.
 Morphological divergence between closely related species can be small