Download Upwelling, Downwelling, and El Nino

DNA and Its Role in Heredity
Molecular Basis of Inheritance
Chapter 9




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
Chapter 9 Opening Question
What can we learn from ancient DNA?
Search for Genetic Material




Looking for a molecule that could be specific and show
great variation
Molecule needs to be abundant
Needs to be able to be copied precisely
What is your guess based on these requirements?
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.
Concept 9.1 DNA Structure Reflects Its Role as the
Genetic Material




The amount of dye that binds to DNA, and thus color intensity, is
related to the amount of DNA present.
The amount of DNA was analyzed in individual cells by passing
them through a flow cytometer.
Cells in G1 contained half the DNA that cells in S, G2, and M
contained.
All nondividing somatic cells have the same amount of DNA;
gametes have half the amount.
Figure 9.1 DNA in the Cell Cycle
Figure 9.1 DNA
in the Cell Cycle
When dividing
cells are stained
and analyzed by
flow cytometry,
there are two
populations in
terms of DNA
content, seen as
two peaks in the
above graph.
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.
Evidence of Genetic Material




Griffith looking for vaccine against Streptococcus
pneumoniae
2 strains: S-smooth colonies; R-rough
S are encapsulated with polysaccharide coat
Alternative phenotypes (S and R) are inherited
Griffith Experiment





Injected live S strain into mice: mice died of pneumonia
(S is pathogenic)
Injected live R strain into mice: mice healthy (R is
nonpathogenic)
Mice injected with heat killed S: mice healthy
Mice injected with heat killed S mixed w live R cells:
mice died
Blood samples from dead mice contained live S cells: R
cell acquired from dead S cells ability to make coats
TRANSFORMATION
Transformation
Implications



Transformation: assimilation of external genetic material
by a cell
Not a protein-heat denatures proteins but heat did not
destroy the transforming ability of the genetic material in
the heat killed S cells
Later Avery, McCarty, and MacLeod discovered
transforming agent was DNA
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.
Evidence of Viral DNA





Bacteriophage (phage): virus that infects bacteria
Alfred Hershey & Martha Chase DNA genetic material
of phage T2
Virus was DNA and a protein coat
Protein tagging: T2 and E. coli were grown
DNA tagging: T2 and E. coli were grown in media w 32
P
Phage structure
Hershey and Chase







Protein labeled infected E. coli
DNA labeled infected separate E. coli
Mixtures were agitated to break loose phage coats from
bacteria
Mixtures were centrifuged; cells in the pellet; viruses in
the supernatant
S labeled in supernatant
P labeled in the pellet
Bacteria P labeled released viruses w P
Hershey and Chase’s Method
Conclusions Hershey & Chase




Viral proteins remain outside the host cell
Viral DNA injected into host cell
Injected DNA molecules cause cells to produce
additional viruses w more viral DNA and proteins
Nuclei acids not proteins are hereditary material
Chargaff’s Experiment





Analyzed DNA of different organisms
DNA composition is species specific: amount and ratios
of nitrogenous bases vary from one species to another
Adenine residues equaled number of thymines;
cytosines equaled number of guanines
Chargaff’s rules A=T; G=C
This molecular diversity supports DNA as hereditary
material
Concept 9.1 DNA Structure Reflects Its Role as the
Material
 In 1950, ErwinGenetic
Chargaff
found the amount of A
always equaled the amount of T, and amount of G
always equaled the amount of C.
Circumstantial Evidence for DNA



Eukaryotic cell doubles DNA content prior to mitosis
During mitosis, the doubled DNA is equally divided btwn
2 daughter cells
Organism’s diploid cells have 2x DNA as haploid
gametes
Concept 9.1 DNA Structure Reflects Its Role as the
Genetic Material


X-ray crystallography: positions of atoms in a
crystallized substance can be inferred from the
diffraction pattern of X rays passing through the
substance
Crystallographs of DNA were prepared in the early
1950s by Rosalind Franklin and suggested a spiral or
helical molecule.
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 nitrogencontaining bases:
– Purines: adenine (A) and guanine (G)
– Pyrimidines: cytosine (C) and thymine (T)
Watson, Crick, & Franklin







Working on 3D structure
Wilkins fed Watson and Crick Franklin’s X ray of DNA
crystal
Watson and Crick deduced:
Helix w uniform width of 2 nm
Purine and pyrimidine bases stacked .34 nm apart
Helix makes 1 full turn 3.4 nm
There are 10 layers of bases in ea turn
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.
 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 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
Concept 9.1 DNA Structure Reflects Its Role as the
Genetic Material
– The outer edges of the nitrogenous bases are
exposed in major and minor grooves.


The grooves exist because the helices are not
evenly spaced.
There are 4 possible configurations of the flat,
hydrogen-bonded base pairs within the major
and minor grooves.
Figure 9.5 DNA Is a Double Helix (Part 2)
Figure 9.6 Base Pairs in DNA Can Interact with Other
Molecules (Part 1)
Figure 9.6 Base Pairs in DNA Can Interact with Other
Molecules (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
– The DNA double helix is right-handed.



It can be found as a much less stable left-handed
helix (Z-DNA or “zig-zag DNA”).
It does not have grooves and is less compact.
Forms in regions where DNA is being transcribed;
it may help stabilize the DNA.
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
DNA Structure




Tried sugar phosphate chains on inside no go
On outside, hydrophobic interactions of nitrogenous
bases pushed them to inside
Ladder twisted into a spiral
2 sugar phosphate backbones of the helix are
antiparallel; they run in opposite directions
One strand of DNA
DNA rungs







Pair of nitrogenous bases
Purine must pair w pyrimidines to get .34 nm
W Chargaff, A purine + T pyrimidine
G purine + C pyrimidine
Suggests mechanisms for DNA replication
Sequences of bases highly variable allowing specificity for
genetic coding
Hydrogen bonds and van der waals stabilize DNA




DNA Replication
Watson & Crick proposed genes on original DNA strand are
copied by specific pairing of complementary bases, creating
a complementary strand
Complementary strand can function as template to produce a
copy of original strand
2 strands separate each acts as template for complementary
strand
Enzymes link nucleotides together at sugar-phosphate
groups
3D models
Meselson and Stahl




3 hypotheses
Conservative: parental double helix remain intact and second DNA
molecule entirely new molecule
Semiconservative: each DNA molecules should be composed of
one original & one new strand
Dispersive: both strands of newly produced DNA molecules should
contain mix of old and new DNA






Meselson & Stahl Experiment
Grew E coli on medium w 15N (heavy nitrogen)
Transferred to medium w 14N
1st generation DNA extracted from E coli after on generation of
growth in light medium
2nd generation DNA extracted from E coli after 2 replications in
light medium
Isolated DNA was mixed w CsCl & centrifuged
Centrifugal force created CsCl gradient w >conc at bottom; DNA
moved to place density matched density of CsCl
Meselson & Stahl Method
Results Meselson & Stahl



Parents: 1 distinct band / tube
1st generation 1 distinct band near center
2nd generation 2 bands one near center other light
Conclusions: Meselson & Stahl



1st generation all hybrid: semiconservative model
1st generation eliminated conservative, but not dispersive
2nd generation eliminated dispersive; only one band would have
occurred if dispersive replication
Semiconservative Replication
DNA Replication





Helical molecule must untwist (helicase) while it copies its two
antiparallel strands simultaneously
Requires 2 dozen enzymes and other proteins
Prokaryotes: 500 nucleotides/sec
Few hours to copy 6 billion bases of single human cell
Accurate: 1 in a billion nucleotides is incorrectly paired
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


During DNA synthesis, new nucleotides are added to
the 3′ end of the new strand, which has a free hydroxyl
group (—OH).
The DNA template is read 3ʹ to 5ʹ, and the new strand
of DNA is generated 5ʹ to 3ʹ, forming an antiparallel
double helix.
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.
Enzymes for Replication
Origins of Replication




DNA replication begins at sites called origins of replication that
have a specific sequence of nucleotides
Specific proteins required to initiate replication bind to origin
DNA double helix opens at origin and replication forks spread in
both directions away from point form replication bubble
Prokaryotes one origin; eukaryotes thousands
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
Elongating a new strand





Helicases are enzymes which catalyze unwinding of parental
double helix
Single strand binding proteins keep strands apart and stabilize the
unwound DNA until new strand can be synthesized
DNA polymerases catalyze synthesis of a new DNA strand
New nucleotides align on template of old
DNA polymerase links nucleotides to growing strand; only grow
from 5’ to 3’ only add to 3’
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.
Replication is endergonic





Requires energy
Nucleoside triphosphate is source
Covalently linked to 5’ carbon of pentose
Nucleoside triphosphate lose 2 phosphates form covalent linkages
to the growing chain
Hydrolysis of phosphate bond drives synthesis of DNA
Antiparallel





Continuous synthesis of both DNA strands is not possible due to
the antiparallel construction
Can only elongate from 5’ to 3’
Continuous synthesis occurs on the leading strand which is 5’ to 3’
The lagging strand (complementary strand) has discontinuous
synthesis
Lagging strand produced as a number of short segments called
Okazaki fragments
Replication of antiparallel strands
Okazaki Fragments



Synthesized in 5’ to 3’ direction
Fragments are 1000-2000 nucleotides in length in bacteria and
100-200 nucleotides long in eukaryotes
Fragments are ligated by DNA ligase, linking enzyme that
catalyzes formation of a covalent bond between the 3’ end of each
new fragment and the 5’ end of the growing chain
primer




Primer is a short RNA segment that is complementary to DNA
segment & that is necessary to begin DNA replication
Primers are polymerized by an enzyme called primase
Portion of parental DNA serves as template for primer w a base
sequence that is about 10 nucleotides long in eukaryotes
Primer formation must precede DNA replication, DNA polymerase
only add nucleotides to a poly nucleotide that is already correctly
base-paired w complementary strand
primers






Only one is needed for leading strand
Thousands are needed for lagging strand
RNA primer must initiate the synthesis of each Okazaki fragment
Fragments are ligated in 2 steps to produce a continuous DNA
strand
DNA polymerase removes the RNA primer and replaces it w DNA;
DNA ligase catalyzes linkage
Between 3’ end of each fragment & 5’ of chain
Enzymes repair damage



Initial pairing errors occur at a frequency of 1 in 10K
DNA can be repaired as it is being synthesized: mismatch repair
DNA polymerase proofreads each newly added nucleotide against
its template; if incorrect removes and replaces it (eukaryotes have
proteins too to proofread)
Excision repair: accidental changes in DNA can result from
exposure; 50 different DNA repair enzymes; one excises and gap
filled by base-pairing by DNA polymerase and DNA ligase
Mismatch repair
Repair Significance
 The importance of proper function of repair enzymes is clear from
the inherited disorder xeroderma pigmentosum.
– These individuals are hypersensitive to sunlight.
– In particular, 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.
Concept 9.2 DNA Replicates Semiconservatively


When the last primer is removed, no DNA synthesis
occurs because there is no 3′ end to extend—a singlestranded bit of DNA is left at each end.
These are cut and the chromosome is slightly shortened
after each replication.
Telomere replication
 Limitations in the DNA polymerase create problems for
the linear DNA of eukaryotic chromosomes.
 The usual replication machinery provides no way to
complete the 5’ ends of daughter DNA strands.
– Repeated rounds of replication produce shorter and
shorter DNA molecules
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
Telomere
 The ends of eukaryotic chromosomal DNA molecules, the
telomeres, have special nucleotide sequences.
– 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.
 Eukaryotic cells have evolved a mechanism to restore
shortened telomeres.
 Telomerase uses a short molecule of RNA as a template to
extend the 3’ end of the telomere.
– 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
Telomerase is not present in most cells of multicellular organisms.
Therefore, the DNA of dividing somatic cells and cultured cells does
tend to become shorter.
Thus, telomere length may be a limiting factor in the life span of
certain tissues and the organism.
Telomerase is present in germ-line cells, ensuring that zygotes
have long telomeres.
Active telomerase is also found in cancerous somatic cells.
– This overcomes the progressive shortening that would
eventually lead to self-destruction of the cancer.
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
 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
Concept 9.2 DNA Replicates Semiconservatively
 PCR
is a cyclic process in which a sequence of steps is
repeated over and over again.
 DNA replication is fast, so it takes only a short time to
make millions of copies.
 The sequences at each end of the amplified fragment
must be known ahead of time, so that complementary
primers can be made.
 A pair of primers will usually bind to only a single region
of DNA in an organism’s genome.
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
 Point
mutations may result in proteins that are less
efficient, but maintain enough function that phenotype is
not changed.
 Or amino acid substitutions may not affect protein
function (e.g., substitution of one hydrophilic amino acid
for another).
Concept 9.3 Mutations Are Heritable Changes in DNA
 The
human gene TP53 encodes the tumor suppressor
protein p53, which normally inhibits the cell cycle.
 A gain-of-function point mutation in TP53 causes the
protein to promote the cell cycle and prevent cell death—
it has a gain of oncogenic function.
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
 DNA
sequencing revealed that mutations occur most
often at certain base pairs.
 These “hotspots” are often located where cytosine has
been methylated to
5-methylcytosine.
 If 5-methylcytosine loses an amino acid, it becomes
thymine, a natural base for DNA.
 During mismatch repair, it is repaired correctly only
half of the time.
Figure 9.19 5-Methylcytosine Is a “Hotspot” for Mutations
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 ozone-depleting
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.
Answer to Opening Question

The Neanderthal Genome Project has extracted DNA
from bones and sequenced the entire genome.

The DNA is over 99% identical to human DNA, justifying
putting neanderthals in the same genus, Homo.

Answer to Opening Question
Interesting findings:
– Some Neanderthals may have had red hair and
fair skin, due to a point mutation in the gene
MC1R.
– Neanderthals may have been capable of speech,
as their vocalization gene FOXP2 was identical to
humans.
– DNA sequences suggest interbreeding of humans
and Neanderthals.
Figure 9.20 A Neanderthal Child
This reconstruction
of a Neanderthal
child who lived
about 60,000 years
ago was made using
bones recovered at
Gibraltar, as well as
phenotypic
projections made
from DNA analyses.