Gene Expression and Control

Chapter 7
Part 2

7.6 Mutated Genes and Their Products

Mutations are permanent changes in the
nucleotide sequence of DNA, which may alter a
gene product
A mutation that changes a genes product may
have harmful effects
Example: Mutations that affect the proteins in
hemoglobin reduce bloods ability to carry oxygen

Types of Mutations
Deletion
Mutation in which one or more base pairs are lost

Insertion
Mutation in which one or more base pairs
become inserted into DNA

Base-pair substitution
Type of mutation in which a single base-pair
changes

Two Common Mutations in Hemoglobin

A Hemoglobin, an oxygen-transport protein in red blood cells. This

protein consists of four globin chains: two alpha chains (blue) and
two beta chains (green). Each globin chain folds up to form a
pocket that cradles a type of cofactor called a heme (red). Oxygen
binds to the iron atom at the center of each heme group.
Fig. 7-9a, p. 125

Fig. 7-9b, p. 125

part of DNA

mRNA transcribed
from DNA

threonine
(thr)

proline
(pro)

glutamic
acid (glu)

glutamic
acid (glu)

lysine
(lys)

resulting amino
acid sequence

B Part of the DNA, mRNA, and amino acid sequence of the beta
chain of a normal hemoglobin molecule.
Fig. 7-9b, p. 125

Fig. 7-9c, p. 125

deletion
in DNA
altered mRNA

threonine
(thr)

proline
(pro)

glycine
(gly)

arginine
(arg)

threonine
(thr)

altered amino
acid sequence

C A single base-pair deletion causes the reading frame for the rest of the
mRNA to shift, so a completely different protein product forms. This
mutation results in a defective globin chain. The outcome is thalassemia, a
genetic disorder in which a person has an abnormally low amount of
hemoglobin.
Fig. 7-9c, p. 125

Fig. 7-9d, p. 125

base-pair
substitution
in DNA
altered mRNA

threonine
(thr)

proline
(pro)

valine
(val)

glutamic
acid (glu)

lysine
(lys)

altered amino
acid sequence

D A base-pair substitution in DNA replaces a thymine with an adenine.

When the altered mRNA is translated, valine replaces glutamate as the
sixth amino acid of the new polypeptide chain. Hemoglobin with this
chain is called HbS, or sickle hemoglobin.
Fig. 7-9d, p. 125

Animation: Base-pair substitution

Sickle-Cell Anemia:
A Base-Pair Substitution

valine
(val)

histidine leucine threonine proline

(thr)
(his)
(leu)
(pro)

glutamic
glutamic
acid
acid
(glu)
(glu)

1 Normal amino acid sequence at the

start of the hemoglobin beta chain.
valine histidine leucine threonine proline
(thr)
(val)
(pro)
(his)
(leu)
2 One amino acid substitution
results in the abnormal beta chain
of sickle hemoglobin (HbS). The
sixth amino acid in such chains
is valine, not glutamic acid.
3 Glutamic acid carries an overall
negative charge; valine carries no
charge. This difference causes the
protein to behave differently. At low
oxygen levels, HbS molecules stick
together and form rod-shaped
clumps that distort normally round
red blood cells into sickle shapes.
(A sickle is a farm tool with a
crescent-shaped blade.)

valine
(val)

glutamic
acid
(glu)

sickled cell

normal cell

4 Tionne T-Boz Watkins of the music

group TLC is a celebrity spokesperson
for the Sickle Cell Disease Association
of America. She was diagnosed with
sickle-cell anemia as a child.
Fig. 7-10a, p. 126

Fig. 7-10b, p. 126

What Causes Mutations?

Most mutations result from unrepaired DNA
polymerase errors during DNA replication
Some result from transposable element activity,
or from exposure to radiation or chemicals

Transposable element
Small segment of DNA that can spontaneously
move to a new location in a chromosome

Ionizing Radiation Damage

Ionizing radiation (x-rays) breaks chromosomes
and produces free radicals

Nonionizing Radiation Damage

Nonionizing radiation (UV light) results in
thymine dimers, which lead to skin cancer

thymine
dimer

Fig. 7-11b, p. 127

Environmental Damage

Some natural and synthetic chemicals cause

mutations in DNA

Example: Cigarette smoke transfers small

hydrocarbon groups to bases in DNA, causing
mispairing during replication

Animation: Frameshift mutation

Animation: Duplication

Animation: Deletion

Animation: Inversion

Animation: Translocation

Animation: Sickle-cell anemia

Animation: Symptoms of sickle cell

anemia

7.7 Examples of
Eukaryotic Gene Controls
All cells in your body carry the same DNA

Some genes are transcribed by all cells, but

most cells are specialized (differentiated) to use
only certain genes
Which genes are expressed at a given time
depends on the type of cell and conditions

Cell Differentiation
Cells differentiate when they start expressing a
unique subset of their genes controls over
gene expression are the basis of differentiation
Differentiation
The process by which cells become specialized
Occurs as different cell lineages begin to express
different subsets of their genes

Controlling Gene Expression

Controlling gene expression is critical for normal
development and function of a eukaryotic body
All steps between transcription and delivery of
gene product are regulated

Transcription factor
Protein that influences transcription by binding to
DNA

Homeotic Genes
Homeotic gene
Type of master gene that controls formation of
specific body parts during development

Master gene
Gene encoding a product that affects the
expression of many other genes
Controls an intricate task such as eye formation

Homeodomains

All homeotic genes encode transcription factors

with a homeodomain a region of about 60
amino acids that can bind to a promoter or some
other DNA sequence

Identifying Homeotic Genes

and Their Functions

Researchers study the function of a homeotic

gene by altering its expression by introducing
a mutation or deleting it entirely
Examples: eyeless, dunce, tinman, groucho

Gene knockout
A gene that has been inactivated in an organism

Gene Knockout Experiment: Eyeless

Fig. 7-12a, p. 128

Fig. 7-12b, p. 128

Fig. 7-12c, p. 128

PAX6 Gene Function

Many master genes are interchangeable among
species; in humans and many other animals, the
PAX6 gene affects eye formation

Fig. 7-12d, p. 128

Fig. 7-12e, p. 128

Sex Chromosome Genes

In mammals, males have only one X

chromosome females have two, but one is
tightly condensed into a Barr body and inactive
Dosage compensation
Theory that X chromosome inactivation equalizes
gene expression between males and females

X Chromosome Inactivation
Female cells have Barr bodies, male cells do not

The Y Chromosome
The SRY gene, found on the Y chromosome, is
the master gene for male sex determination
Triggers formation of testes
Testosterone produced by testes controls
formation of male secondary traits

Absence of SRY gene in females triggers

development of ovaries, female characteristics

Development of
Human Reproductive Organs

Structures that will give rise

to external genitalia appear
at seven weeks

SRY expressed

no SRY present

penis
vaginal
opening

birth approaching
Fig. 7-14, p. 129

Cancer: Gene Expression Out of Control

Many gene expression controls regulate cell

growth and division mutations that disrupt
normal controls can cause cancer
Cancer
Disease that occurs when a malignant neoplasm
physically and metabolically disrupts body tissues

Tumors

Tumor
Abnormally growing and dividing mass of cells

Metastasis
A process of cancer in which tumor cells lose
membrane recognition proteins, break free, and
establish themselves in other parts of the body

Cancer and Mutations

Cancer begins with a mutation in a gene whose
product controls cell growth and division
A mutation that causes cancer may be inherited
or be caused by environmental agents

Tumors are more likely to occur when mutations

occur in tumor suppressor genes, such as
BRCA1 and BRCA2

BRCA Genes and Cancer

Fig. 7-15a, p. 130

Fig. 7-15b, p. 130

normal cells in
organized clusters

irregular clusters
of cancer cells

Fig. 7-15b, p. 130

Animation: Controls of eukaryotic gene

expression

Animation: Fate map

Animation: X-chromosome inactivation

Animation: Protein synthesis summary

7.8 Impacts/Issues Revisited

Ricin causes ribosomes to stop working

protein synthesis stops, and the cell quickly dies

Researchers are trying to kill cancer cells

without harming normal cells by attaching ricin to
an antibody that can find cancer cells in the body

Digging Into Data: BRCA Mutations

in Women Diagnosed with Breast Cancer