Chapter9 Lecture Powerpoint Full

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9
DNA and Its Role in Heredity
Chapter 9 DNA and Its Role in Heredity
Key Concepts
9.1 DNA Structure Reflects Its Role as the
Genetic Material
9.2 DNA Replicates Semiconservatively
9.3 Mutations Are Heritable Changes in DNA
Concept 9.1 DNA Structure Reflects Its Role as the Genetic
Material
By the early 20th century, a “chromosomal
theory of inheritance” had been developed,
proposing that Mendel’s genes are on the
chromosomes.
Then evidence began to accumulate indicating
that DNA is the genetic material.
Concept 9.1 DNA Structure Reflects Its Role as the Genetic
Material
Circumstantial evidence:
• DNA is present in the cell nucleus and in
chromosomes.
• It doubles during S phase of the cell cycle.
• There is twice as much in diploid cells as in
haploid cells.
Concept 9.1 DNA Structure Reflects Its Role as the Genetic
Material
DNA was first isolated in 1868 from white
blood cell nuclei.
The young Swiss researcher called the fibrous
substance “nuclein,” and proposed that it
was the genetic material.
It was composed of C, H, O, N, and P.
Concept 9.1 DNA Structure Reflects Its Role as the Genetic
Material
Dyes were developed in the early 20th century
that showed color when bound to DNA in
dividing cells.
Figure 9.1 DNA in the Cell Cycle
Concept 9.1 DNA Structure Reflects Its Role as the Genetic
Material
Chromosomes contain DNA, but also
proteins, so scientists had to rule out
proteins as the genetic material.
In transformation experiments, it was shown
that DNA from one strain of bacterium could
genetically transform another strain:
strain A + strain B DNA → bacterium strain B
Concept 9.1 DNA Structure Reflects Its Role as the Genetic
Material
Viruses such as bacteriophage contain DNA
and a little protein.
Experiments showed that when a virus infects
a bacterium, it injects only its DNA.
Since the viral DNA genetically transforms the
bacteria, this was further evidence for DNA
as the genetic material.
Figure 9.2 Viral DNA and Not Protein Enters Host Cells
Figure 9.3 Transformation of Eukaryotic Cells (Part 1)
Figure 9.3 Transformation of Eukaryotic Cells (Part 2)
Concept 9.1 DNA Structure Reflects Its Role as the Genetic
Material
Egg cells can also be transformed in this way,
resulting in a whole new genetically
transformed organism—called transgenic.
These methods form the basis of much
applied research, including biotechnology
and genetic engineering, and have
provided strong evidence for DNA as the
genetic material.
Figure 9.4 X-Ray Crystallography Helped Reveal the Structure of DNA
Concept 9.1 DNA Structure Reflects Its Role as the Genetic
Material
Chemical composition:
Biochemists knew that nucleotides consisted of
the sugar deoxyribose, a phosphate group,
and nitrogen-containing bases:
• Purines: adenine (A) and guanine (G)
• Pyrimidines: cytosine (C) and thymine (T)
• (Pneumonic: CARS get parked in the
GARAGE, APPLES grow on TREES)
Concept 9.1 DNA Structure Reflects Its Role as the Genetic
Material
In 1950, Erwin Chargaff found the amount
of A always equaled the amount of T, and
amount of G always equaled the amount
of C.
Concept 9.1 DNA Structure Reflects Its Role as the Genetic
Material
3-D model building:
Francis Crick and James Watson combined all
the knowledge of DNA to determine its
structure: Double Helix
Franklin’s X-ray crystallography convinced
them the molecule was helical.
Density measurements suggested there are two
polynucleotide chains in the molecule.
Modeling showed that DNA strands must be
antiparallel.
Figure 9.5 DNA Is a Double Helix (Part 1)
Figure 9.5 DNA Is a Double Helix (Part 2)
Concept 9.1 DNA Structure Reflects Its Role as the Genetic
Material
Watson and Crick suggested that:
• The bases (B) are on the interior of the
two strands, with a sugar-phosphate
backbone on the outside.
Concept 9.1 DNA Structure Reflects Its Role as the Genetic
Material
• Per Chargaff’s rule, a purine on one
strand is paired with a pyrimidine on the
other, making the base pairs (A–T and
G–C) the same width down the helix.
Concept 9.1 DNA Structure Reflects Its Role as the Genetic
Material
Four key features of DNA structure:
• Double-stranded helix of uniform
diameter

The chains are held together by
hydrogen bonds between the base
pairs and by van der Waals forces
between adjacent bases on the same
strand.
Concept 9.1 DNA Structure Reflects Its Role as the Genetic
Material
• The two strands are antiparallel.

In the sugar–phosphate backbone, the
phosphate groups are bonded to the 5ʹ
carbon of one sugar and the 3ʹ carbon
of the next.
Figure 3.4 DNA
Figure 9.5 DNA Is a Double Helix (Part 2)
Concept 9.1 DNA Structure Reflects Its Role as the Genetic
Material

The surfaces of A–T and G–C base
pairs are chemically distinct.

Binding of proteins to specific base
pair sequences is key to DNA–
protein interactions, which are
necessary for replication and gene
expression.
Concept 9.1 DNA Structure Reflects Its Role as the Genetic
Material
DNA structure is essential to its functions:
• Storage of genetic information
• Precise replication during cell division by
complementary base pairing
• Susceptibility to mutations (stable
changes in the genetic material)
• Expression of the coded information as
the phenotype
Concept 9.2 DNA Replicates Semiconservatively
Semiconservative replication: each parental
strand is a template for a new strand.
Concept 9.2 DNA Replicates Semiconservatively
Two general steps in DNA replication:
• The double helix is unwound, making
two template strands available for new
base pairing.
• Nucleotides form base pairs with
template strands and are linked together
by phosphodiester bonds.
Figure 9.7 Each New DNA Strand Grows by the Addition of Nucleotides to Its 3ʹ End
Concept 9.2 DNA Replicates Semiconservatively
DNA is synthesized from
deoxyribonucleoside triphosphates
(dNTPs) or deoxyribonucleotides.
During synthesis, two of the phosphate
groups are released, and the final nucleotide
is a monophosphate (adenine, thymine,
cytosine, or guanine).
Release of the two outer phosphate groups
provides energy for formation of a
phosphodiester bond.
Concept 9.2 DNA Replicates Semiconservatively
DNA replication begins with the binding of a
large protein complex (pre-replication
complex) to a specific site on the DNA
molecule called the origin of replication
(ori).
The complex contains DNA polymerase,
which catalyzes addition of nucleotides.
Concept 9.2 DNA Replicates Semiconservatively
In prokaryotes, the pre-replication complex
binds to ori, the DNA unwinds, and
replication proceeds in two directions.
The replication fork is the site where DNA
unwinds.
Opening of each fork is catalyzed by DNA
helicase.
Figure 9.8 The Origin of DNA Replication
Concept 9.2 DNA Replicates Semiconservatively
Eukaryotic chromosomes are much longer,
are linear, and have multiple origins of
replication, which speed up replication.
It would take weeks to fully replicate a
chromosome from a single ori.
Concept 9.2 DNA Replicates Semiconservatively
DNA replication begins with a short primer or
starter strand, usually a short single strand
of RNA.
The primer is complementary to the DNA
template and is synthesized by a primase.
DNA polymerase then adds nucleotides to the
3ʹ end of the primer and continues until
replication of that section is completed.
Figure 9.9 DNA Forms with a Primer
Concept 9.2 DNA Replicates Semiconservatively
DNA polymerases are very large and
shaped like an open right hand.
The “palm” brings the active site and the
substrates into contact.
The “fingers” recognize the nucleotide bases.
The enzyme then changes shape and
catalyzes formation of a new phosphodiester
bond.
Figure 9.10 DNA Polymerase Binds to the Template Strand
Concept 9.2 DNA Replicates Semiconservatively
The leading strand is oriented to grow
continuously at its 3′ end as the fork opens.
The lagging strand is oriented so that its
exposed 3′ end gets farther from the fork.
Synthesis of the lagging strand occurs in
small, discontinuous stretches called
Okazaki fragments.
Figure 9.11 The Two New Strands Form in Different Ways
Concept 9.2 DNA Replicates Semiconservatively
Each Okazaki fragment requires its own
primer.
DNA polymerase adds nucleotides to the 3′
end until reaching the primer of the previous
fragment.
A different DNA polymerase then replaces the
primer with DNA.
The final phosphodiester linkage between
fragments is catalyzed by DNA ligase.
Figure 9.12 The Lagging Strand Story (Part 1)
Figure 9.12 The Lagging Strand Story (Part 2)
Concept 9.2 DNA Replicates Semiconservatively
DNA polymerase works very fast but makes
very few errors.
It is processive—it catalyzes many
sequential polymerization reactions each
time it binds to DNA.
A DNA polymerase can add thousands of
nucleotides before it detaches from DNA.
Figure 9.13 Telomeres and Telomerase
Concept 9.2 DNA Replicates Semiconservatively
Chromosome ends must be protected from
being joined to other chromosomes by the
DNA repair system.
Telomeres are repetitive sequences at the
ends of eukaryotic chromosomes.
The repeats bind a protein complex called
shelterin, which protects the ends from being
joined together.
The repeats also form loops, which are also
protective.
Figure 9.13 Telomeres and Telomerase
Concept 9.2 DNA Replicates Semiconservatively
After 20–30 cell divisions, the chromosome
ends become too short, the chromosomes
lose their integrity, and apoptosis ensues.
But continuously dividing cells like bone
marrow and gametes maintain their
telomeric DNA.
• Telomerase catalyzes the addition of lost
telomeric sequences. It has an RNA
sequence that acts as a template for the
telomeric DNA.
Concept 9.2 DNA Replicates Semiconservatively
Telomere lengths tend to shorten with
aging.
If a gene expressing high levels of telomerase
is added to human cells in culture, their
telomeres do not shorten, and the cells
become immortal.
This is also seen in mice that overexpress
telomerase—they live longer.
Cancer cells also express telomerase.
Concept 9.2 DNA Replicates Semiconservatively
DNA polymerases can make mistakes in
replication, but most errors are repaired.
Two major repair mechanisms:
• Proofreading—DNA polymerase has a
proofreading function, and if bases are
paired incorrectly, the nucleotide is
removed.
• Mismatch repair—after replication, other
proteins scan for mismatched bases
missed in proofreading and replace them
with correct ones.
Figure 9.14 DNA Repair Mechanisms
Concept 9.2 DNA Replicates Semiconservatively
Copies of DNA sequences can be made by
the polymerase chain reaction (PCR)
using:
• A double-stranded DNA sample
• Two primers complementary to the ends
of the sequence to be copied
• The four dNTPs
• A DNA polymerase that works at high
temperatures
• Salts and a buffer to maintain pH
Figure 9.15 The Polymerase Chain Reaction
Concept 9.3 Mutations Are Heritable Changes in DNA
Mutations are changes in the nucleotide
sequence of DNA that are passed on from
one cell or organism to another.
Mutations occur by a variety of processes,
including replication errors that are not
corrected by repair systems.
Concept 9.3 Mutations Are Heritable Changes in DNA
Somatic mutations occur in somatic (body)
cells. They are passed on by mitosis but not
to sexually produced offspring.
Germ line mutations occur in germ line cells
that give rise to gametes. A gamete with a
mutation passes it on to the new organism at
fertilization.
Mutations may or may not affect the
phenotype.
Concept 9.3 Mutations Are Heritable Changes in DNA
Silent mutations do not affect protein
function.
Loss of function mutations prevent gene
transcription or produce nonfunctional
proteins; nearly always recessive.
Gain of function mutations lead to a protein
with altered function. Usually dominant;
common in cancer cells.
Figure 9.16 Mutation and Phenotype
Concept 9.3 Mutations Are Heritable Changes in DNA
Conditional mutations cause phenotypes
under restrictive conditions, such as
temperature (e.g., point restriction coat
color in cats and rabbits).
The wild-type phenotype is expressed under
other, permissive conditions.
Concept 9.3 Mutations Are Heritable Changes in DNA
A point mutation results from the gain, loss,
or substitution of a single nucleotide.
• Can arise from replication errors or be
caused by environmental mutagens such
as radiation or certain chemicals.
Concept 9.3 Mutations Are Heritable Changes in DNA
Point mutations may alter the amino acid
sequence in a protein with drastic
effects.
The sickle-cell disease allele differs from the
normal by one base pair, resulting in a
polypeptide with only one different amino
acid.
Concept 9.3 Mutations Are Heritable Changes in DNA
Chromosomal mutations are extensive
changes in genetic material involving whole
chromosomes.
They can result from mutagens or drastic
errors in replication.
They can provide new combinations of genes
and genetic diversity important to evolution
by natural selection.
Concept 9.3 Mutations Are Heritable Changes in DNA
Chromosomal mutations:
• Deletions—loss of a chromosome
segment; can have severe or fatal
consequences
• Duplications—homologous
chromosomes break in different places
and recombine with wrong partners; one
may have two copies of the segment and
the other may have none
Concept 9.3 Mutations Are Heritable Changes in DNA
Inversions result from breaking and rejoining,
but the segment is “flipped.”
Translocations—segment of DNA breaks off
and is inserted into another chromosome;
can lead to duplications and deletions
Figure 9.17 Chromosomal Mutations
Concept 9.3 Mutations Are Heritable Changes in DNA
Spontaneous mutations occur with no
outside influence.
• Replication errors by DNA polymerase—
most are repaired but some become
permanent.
• Nucleotide bases can exist in 2 forms
(tautomers), one common and one rare. A
rare tautomer can pair with the wrong
base.
Figure 9.18 Spontaneous and Induced Mutations (Part 1)
Concept 9.3 Mutations Are Heritable Changes in DNA
• Spontaneous chemical reactions may
change bases (e.g., deamination)
• Errors in meiosis such as nondisjunction
and aneuploidy or chromosomal
breakage and rejoining.
• Gene sequences can be disrupted—
random chromosome breakage and
rejoining can produce deletions,
duplications, inversions, or translocations.
Concept 9.3 Mutations Are Heritable Changes in DNA
Induced mutations are caused by mutagens:
• Chemicals can alter nucleotide bases (e.g.,
nitrous acid can cause deamination)
• Some chemicals add other groups to bases
(e.g., benzopyrene adds a group to guanine
and prevents base pairing).
Figure 9.18 Spontaneous and Induced Mutations (Part 2)
Concept 9.3 Mutations Are Heritable Changes in DNA
• Ionizing radiation, such as X rays, can
detach electrons from atoms and form
highly reactive free radicals that can
change bases and break sugar
phosphate bonds.
• UV radiation (from sun or tanning lamps)
is absorbed by thymine, causing it to form
covalent bonds with adjacent nucleotides;
disrupts DNA replication.
Figure 9.18 Spontaneous and Induced Mutations (Part 3)
Concept 9.3 Mutations Are Heritable Changes in DNA
Many mutagens are naturally occurring.
Plants and fungi make many chemicals for
defense; some can be mutagenic, such as
aflatoxin made by the mold Aspergillus.
Radiation can be natural, such as UV from the
sun, or human-made, such as radiation from
nuclear bombs.
There are about 16,000 DNA-damaging
events per cell per day, of which 80% are
repaired.
Concept 9.3 Mutations Are Heritable Changes in DNA
Mutations can have benefits:
• Provides the raw material for evolution
in the form of genetic diversity
• Diversity may benefit the organism
immediately—if mutation is in somatic
cells
• Mutations in germ line cells may cause an
advantageous change in offspring
Concept 9.3 Mutations Are Heritable Changes in DNA
Mutations can be harmful if they result in
loss of function of genes or other DNA
sequences needed for survival.
Harmful mutations in germ line cells can be
passed to offspring.
• If heterozygotes for the mutation mate
and produce a homozygote, the mutation
can be lethal.
Harmful mutations in somatic cells can lead to
cancer.
Concept 9.3 Mutations Are Heritable Changes in DNA
We try to minimize exposure to mutagens.
Many things that cause cancer are mutagens.
Benzopyrene is found in coal tar, car
exhaust, charbroiled foods, and cigarette
smoke.
Public policies help reduce exposure:
• Bans on cigarette smoking
• International treaties banning ozonedepleting chemicals
Answer to Opening Question
Ancient DNA is usually destroyed in the
fossilization process.
But intact DNA can be found in frozen
specimens and the interior of bones.
PCR can amplify tiny amounts of DNA for
sequencing, but samples are easily
contaminated.
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