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Chapter 12

GENETIC ENGINEERING AND


THE MOLECULES OF LIFE

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Contents

12.1 The Chemistry of Heredity


12.2 The Double Helix of DNA
12.3 Cracking the Chemical Code
12.4 Protein Structure and Activity: Form and Function
12.5 The Human Genome Project
12.6 Genetically Engineered Medical Treatments
12.7 Genetically Engineered Agriculture
12.8 Cloning Mammals and Humans
12.9 The New Prometheus?

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The Chemistry of Heredity
Genetics: Fundamentals
Human Genome:
- 10 million million
(10x1012) cells with a
nucleus
- each cell has a complete
set of genetic
instructions to make
another you(biologically)
- 23 pairs of chromosomes
- 100,000 genes

- def’n: totality of human


hereditary information in
molecular form

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DNA
DNA (deoxyribonucleic acid):
molecule that carries genetic
information in all species

- DNA of one cell unraveled = 2


meters long

3 parts to DNA:

(i) Phosphate group


(ii) Sugar (deoxyribose)
(iii) Nitrogen bases

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DNA
Put all 3 groups together,
called a nucleotide

Adenosine phosphate

A DNA molecule consists of


thousands of nucleotides put
together in a long chain (left)

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The percenst base composition of DNA
for various species

Common
Species Adenine Thymine Guanine Cytosine
Name
Homo sapiens Human 31.0 31.5 19.1 18.4
Drosophila melanogaster Fruit fly 27.3 27.6 22.5 22.5
Zea mays Corn 25.6 25.3 24.5 24.6
Neuspora crassa Mold 23.0 23.3 27.1 26.6
Escherichia coli Bacterium 24.6 24.3 25.5 25.6
Bacillus subtillis Bacterium 28.4 29.0 21.0 21.6

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The Double Helix of DNA
X-Ray Diffraction of DNA

• R. Franklin • J. Watson & F. Crick


• 1962 Nobel in Chemsitry

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DNA
Turns out that:

Adenine bonds with


Thymine

Guanine binds with


Cytosine

Called
complementary
bases:
A=T
G=C

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DNA Double Helix
DNA is double stranded and
is shaped like a spiral
staircase.

Ex. What is the


complementary strand of
DNA for the following
sequence:

ATAGCCG

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DNA Replication

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Cracking the Chemical Code
DNA: Blueprint of Life?
How does DNA provide genetic information, where does the
information come from?

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DNA: Blueprint of Life?
How does DNA provide genetic information, where does the
information come from?

Key is in the sequences of nitrogen bases.

DNA: blueprint for making proteins

Proteins: made up of amino acids

consist of/or regulate everything in the


chemistry of life

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DNA to Proteins
OK, the instructions are in the sequence of bases.
There are 20 amino acids

How many bases encode for an amino acid?

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DNA to Proteins
OK, the instructions are in the sequence of bases.
There are 20 amino acids

How many bases encode for an amino acid?


if it were 1 base = 1 amino acid, then there would only
be 4 amino acids found in proteins. There are up to 20
amino acids found in proteins.

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DNA to Proteins
OK, the instructions are in the sequence of bases.
There are 20 amino acids

How many bases encode for an amino acid?


if it were 1 base = 1 amino acid, then there would only
be 4 amino acids found in proteins. There are up to 20
amino acids found in proteins.

if it were 2: 42 = 16, not enough

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DNA to Proteins
OK, the instructions are in the sequence of bases.
There are 20 amino acids

How many bases encode for an amino acid?


if it were 1 base = 1 amino acid, then there would only
be 4 amino acids found in proteins. There are up to 20
amino acids found in proteins.

if it were 2: 42 = 16, not enough

3 bases: 43 = 64 3 bases = codon

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Codon table

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DNA to Proteins
Transcription: DNA to mRNA

Translation: mRNA to protein

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Protein Structure and Activity:
Form and Function
Polypeptide
Backbone

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Protein structure

• The peptide bond allows for rotation around it and


therefore the protein can fold and orient the R
groups in favorable positions
• Weak non-covalent interactions will hold the
protein in its functional shape – these are weak
and will take many to hold the shape

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Secondary structures

• 2 regular folding patterns


have been identified –
formed between the
bonds of the peptide
backbone
• -helix – protein turns like
a spiral – fibrous proteins
(hair, nails, horns)
• -sheet – protein folds
back on itself as in a
ribbon –globular protein

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Tertiary structure

• The overall fold result in increase in stability


• The shape is maintained through H-bond,
intermolecular ionic and covalent bond and
interactions of amino acid residues with water
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Protein function
– Enzymes, exp : chymotrypsin
– Structural, exp: collagen, hair
– Transport : hemoglobin
– etc
– Sickle cell anemia
differs from normal
blood cell due to
replacement of
hemoglobin amino acid
two glutamic acid by
valine
– Hemoglobin is a
transport protein

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The Human Genome Project
What is the Human Genome Project?

• International effort to map all gene in human organism


• Started in 1989 lead by J. Watson
• Finished June 26, 2000 (co-announced by President Bill Clinton
and PM Tony Blair)

Definition: GENOME – the whole hereditary information of an


organism that is encoded in the DNA.
• Aims of the project:
– to identify the approximate 100,000 genes in the human DNA.
– determine the sequences of the 3 billion bases that make up human
DNA.
– store this information in databases.
– develop tools for data analysis.
– address the ethical, legal, and social issues that arise from genome
research.
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Whose genome is being sequenced?

- the first reference genome is a composite genome


from several different people.
- generated from 10-20 primary samples taken from
numerous anonymous donors across racial and ethnic
groups.

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Benefits of Human Genome Project research

• improvements in medicine.
• microbial genome research for
fuel and environmental
cleanup.
• DNA forensics.
• improved agriculture and
livestock.
• better understanding of
evolution and human migration.
• more accurate risk assessment.

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Genetically Engineered
Medical Treatment
Recombinant DNA: manipulating gene pools
Cut out DNA that encodes for
human insulin

Splice it into E. Coli plasmid


(DNA)

Ecoli reads DNA and starts


making insulin.

Human Growth Hormone


(HGH): previously, a 1 year
supply required harvesting
the pituitary glands from 80
human cadavers
• DNA recombinant
technology offers many
biocatalysis
• Greener reaction
condition

• Atorsvastatin produced from (R)-4-cyano-3-


hydroxybutyrate which was produced by
process using biocatalyst (enzyme)
• The enzyme was a product of DNA
recombinant
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Genetically Engineered
Agriculture
Transgenic plants (organisms)

• Artificially created higher plants and animals that


share the genes of another species
• The focus of development
– Improve production stability
– Give nutritional benefits to the consumer
– Reduce environmental effect of intensive and
extensive agriculture
– Increase the availability of pharmaceutical and
vaccines

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How to create transgenic plants
Agrobacterium tumefaciens

DNA containing Plant cell


gene for desired trait

Ti Recombinant
plasmid Insertion of gene Ti plasmid Introduction Regeneration
into plasmid using into plant of plant
restriction enzyme cells in
T DNA and DNA ligase culture
T DNA carrying new
gene within plant chromosome Plant with new trait
Restriction site
• Nitrogen fixing corn,
corn that capable in • Transgenic soybeans
fixing N2 which is resistance to
• Contain nitrogen fixing herbicides
bacterial genes

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Mixing Genes: Transgenic Organisms
Cloning Mammals and
Humans
Do you know these movies?

Jurassic Park
The Lost World
The Boys from Brazil
Sleeper.
Multiplicity
Invasion of the Body Snatchers
Stepford Wives
A Stolen Life
Clones
The Clones of Bruce Lee
Blade Runner
Star Wars.
Judge Dredd
American Ninja 2
Twins
Gattaca
Alien Resurrection

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Nuclear transfer/ Somatic cell nuclear
transfer
(A, B) nucleus is sucked of cell
(C) New nucleus is picked up
(D) Nucleus/DNA is inserted
into the egg

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Dolly, 1996-2003

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Snuppy, 2005

Snuppy and his Snuppy and his


“father” surrogate mother

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Human cloning

• Many reports said the success of the somatic


nuclear transfer
• After electrical jolt, the embryo started growing
• No report of embryo development to human
• The intention of researcher is to harvest stem cell

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The New Prometheus?
PROMETHEUS
• PROMETHEUS was the Titan god of forethought and crafty
counsel who was entrusted with the task of moulding mankind
out of clay. His attempts to better the lives of his creation
brought him into direct conflict with Zeus. Firstly he tricked the
gods out of the best portion of the sacrificial feast, acquiring
the meat for the feasting of man. Then, when Zeus withheld
fire, he stole it from heaven and delivered it to mortal kind
hidden inside a fennel-stalk. As punishment for these
rebellious acts, Zeus ordered the creation of Pandora (the first
woman) as a means to deliver misfortune into the house of
man, or as a way to cheat mankind of the company of the
good spirits. Prometheus meanwhile, was arrested and bound
to a stake on Mount Kaukasos where an eagle was set to feed
upon his ever-regenerating liver (or, some say, heart).
Generations later the great hero Herakles came along and
released the old Titan from his torture.
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Prometheus

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• We have found key natural compounds of life
“DNA”
• We have clone gene and took many advantage
for human being
• We have clone animals
• Next logical step would be creating new organism
or cloning human “the super one”
• However we could not removed defective gene
from the pools
• And cloning or creating superman could end up
with creating a new prometheus

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Thank you

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