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Genetics: Analysis and Principles
Robert J. Brooker
CHAPTER 16
GENE MUTION
AND DNA REPAIR
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INTRODUCTION

The term mutation refers to a heritable change in
the genetic material

Mutations provide allelic variations



On the positive side, mutations are the foundation for
evolutionary change
On the negative side, mutations are the cause of many
diseases
Since mutations can be quite harmful, organisms
have developed ways to repair damaged DNA
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16-2
16.1 CONSEQUENCES OF
MUTATIONS

Mutations can be divided into three main
types

1. Chromosome mutations


2. Genome mutations


Changes in chromosome number
3. Single-gene mutations


Changes in chromosome structure
Relatively small changes in DNA structure that occur
within a particular gene
Type 3 will be discussed in this chapter
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16-3
Gene Mutations Change the
DNA Sequence

A point mutation is a change in a single base pair

It involves a base substitution
5’ AACGCTAGATC 3’
3’ TTGCGATCTAG 5’



5’ AACGCGAGATC 3’
3’ TTGCGCTCTAG 5’
A transition is a change of a pyrimidine (C, T) to
another pyrimidine or a purine (A, G) to another purine
A transversion is a change of a pyrimidine to a purine or
vice versa
Transitions are more common than transversions
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16-4
Gene Mutations Change the
DNA Sequence

Mutations may also involve the addition or deletion
of short sequences of DNA
5’ AACGCTAGATC 3’
3’ TTGCGATCTAG 5’
5’ AACGCGC 3’
3’ TTGCGCG 5’
Deletion of four base pairs
5’ AACGCTAGATC 3’
3’ TTGCGATCTAG 5’
5’ AACAGTCGCTAGATC 3’
3’ TTGTCAGCGATCTAG 5’
Addition of four base pairs
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16-5
Gene Mutations Can Alter the
Coding Sequence Within a Gene

Silent mutations are those base substitutions that do not
alter the amino acid sequence of the polypeptide


Due to the degeneracy of the genetic code
Missense mutations are those base substitutions in which
an amino acid change does occur

If the substituted amino acids have similar chemistry, the mutation
is said to be neutral
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16-6
Gene Mutations Can Alter the
Coding Sequence Within a Gene

Nonsense mutations are those base substitutions that
change a normal codon to a termination codon

Frameshift mutations involve the addition or deletion of
nucleotides in multiples of one or two

This shifts the reading frame so that a completely different amino
acid sequence occurs downstream from the mutation
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16-7
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16-8
Figure 15-1
Copyright © 2006 Pearson Prentice Hall, Inc.
Gene Mutations and Their Effects
on Genotype and Phenotype

In a natural population, the wild-type is the most
common genotype

A forward mutation changes the wild-type genotype
into some new variation

A reverse mutation has the opposite effect

It is also termed a reversion
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16-9


When a mutation alters an organism’s phenotypic
characteristics, it is said to be a variant
Variants are characterized by their differential ability
to survive:

Deleterious mutations decrease the chances of survival



The most extreme are lethal mutations
Beneficial mutations enhance the survival or reproductive
success of an organism
Conditional mutants: affect the phenotype only
under a defined set of conditions
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16-10

Second-site mutations: suppressor mutations

Intragenic suppressors


The second mutant site is within the same gene as the
first mutation
Intergenic suppressors

The second mutant site is in a different gene from the
first mutation
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16-11
Gene Mutations in Noncoding
Sequences

A mutation, may alter the sequence within a
promoter

Up promoter mutations make the promoter more like the
consensus sequence


Down promoter mutations make the promoter less like the
consensus sequence


They may increase the rate of transcription
They may decrease the rate of transcription
Refer to Table 16.2 for other examples
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16-12
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16-13
Changes in Chromosome Structure
Can Affect Gene Expression


A chromosomal rearrangement may affect a gene
because the break occurred in the gene itself
A gene may be left intact, but its expression may be
altered because of its new location


This is termed a position effect
There are two common reasons for position effects:

1. Movement to a position next to regulatory sequences


Refer to Figure 16.2a
2. Movement to a position in a heterochromatic region

Refer to Figure 16.2b AND 16.3
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16-19
Regulatory sequences
are often bidirectional
Figure 16.2
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16-20
Mutations Can Occur in
Germ-Line or Somatic Cells

Germ-line mutations are those that occur directly in
a sperm or egg cell, or in one of their precursor
cells


Refer to Figure 16.4a
Somatic mutations are those that occur directly in a
body cell, or in one of its precursor cells

Refer to Figure 16.4b AND 16.5
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16-21
The size of the patch
will depend on the
timing of the mutation
The earlier the mutation,
the larger the patch
An individual who has
somatic regions that are
genotypically different
from each other is called
a genetic mosaic
Therefore, the
mutation can be
passed on to future
generations
Figure 16.4
Therefore, the mutation cannot be
passed on to future generations
16-22
16.2 OCCURRENCE AND
CAUSES OF MUTATION

Mutations can occur spontaneously or be induced

Spontaneous mutations

Result from abnormalities in cellular/biological processes


Induced mutations


Caused by environmental agents
Agents that are known to alter DNA structure are termed
mutagens


Errors in DNA replication, for example
These can be chemical or physical agents
Refer to Table 16.4
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16-23
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16-24
Spontaneous Mutations Are
Random Events

Are mutations spontaneous occurrences or causally
related to environmental conditions?

This is a question that biologists have asked themselves
for a long time 

Jean Baptiste Lamarck


Proposed that physiological events (e.g. use and disuse) determine
whether traits are passed along to offspring
Charles Darwin

Proposed that genetic variation occurs by chance

Natural selection results in better-adapted organisms
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16-25

These two opposing theories of the 19th century
were tested in bacteria in the 1940s and 1950s

Salvadore Luria and Max Delbruck studied the
resistance of E. coli to bacteriophage T1


tonr (T one resistance)
They wondered if tonr is due to spontaneous mutations or
to a physiological adaptation that occurs at a low rate?


The physiological adaptation theory predicts that the number of
tonr bacteria is essentially constant in different bacterial populations
The spontaneous mutation theory predicts that the number of
tonr bacteria will fluctuate in different bacterial populations

Their test therefore became known as the fluctuation test
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16-26
E.. coli is grown in the
absence of T1 phages
20 million
cells each
Plates containing T1 phages
Relatively even distribution of tonr colonies
20 million
cells each
Great fluctuation in the number of tonr colonies
Several independent tonr mutations
occurred during different stages
These are mixed together
in a big flask to give
an average value of tonr cells
Figure 16.6
No tonr bacteria
Spontaneous mutation
did not occur
Many tonr bacteria
Mutation occurred at an early stage of
population growth, before T1 exposure
The Luria-Delbruck fluctuation test
16-27
Random Mutations Can Give an
Organism a Survival Advantage


Joshua and Ester Lederberg were also interested in
the relation between mutations and the environment
At that time (1950s), there were two new theories

Directed mutation theory

Selected conditions could promote the formation of specific
mutations allowing the organism to survive


This was consistent with Lamarck’s viewpoint
Random mutation theory

Environmental factors simply select for the survival of those
individuals that happen to possess beneficial mutations

This was consistent with Darwin’s viewpoint
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16-28

The Lederbergs developed
a technique to distinguish
between these two theories

A few tonr colonies were
observed at the same
location on both plates!!!
This indicates that mutations
conferring tonr occurred
randomly on the primary
(nonselective plate)
The presence of T1 in the
secondary plates simply
selected for previously
occurring tonr mutants
This supports the random
mutation theory



Figure 16.7 Replica plating
16-29
Mutation Rates and Frequencies

The term mutation rate is the likelihood that a gene
will be altered by a new mutation



The mutation rate for a given gene is not constant


It is commonly expressed as the number of new mutations
in a given gene per generation
It is in the range of 10-5 to 10-9 per generation
It can be increased by the presence of mutagens
Mutation rates vary substantially between species
and even within different strains of the same species
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16-30
Mutation Rates and Frequencies

Within the same individual, some genes mutate at a
much higher rate than other genes

Some genes are larger than others


Some genes have locations within the chromosome that
make them more susceptible to mutation


This provides a greater chance for mutation
These are termed hot spots
Note: Hot spots can be also found within a single gene

Refer to Figure 6.20
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16-31
Contain many mutations
at exactly the same site
within the gene
Figure 6.20
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16-32
Table 15-2
Copyright © 2006 Pearson Prentice Hall, Inc.
Mutation Rates and Frequencies

The mutation frequency for a gene is the number of
mutant genes divided by the total number of genes
in a population

If 1 million bacteria were plated and 10 were mutant
-5
 The mutation frequency would be 1 in 100,000 or 10

The mutation frequency depends not only on the
mutation rate, but also on the


Timing of the mutation
Likelihood that the mutation will be passed on to future
generations
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16-33
Figure 15-8
Copyright © 2006 Pearson Prentice Hall, Inc.
Figure 15-9
Copyright © 2006 Pearson Prentice Hall, Inc.
Nucleotide Excision Repair
Figure 16.19
16-73
Recombination during DNA
replication
DNA strands A and C have
the same sequence
DNA strands B and D have
the same sequence
Note: Recombinational
repair occurs while the two
DNA copies are being made
Figure 16.22
16-81
The gap has been repaired;
but the thymine dimer remains
Figure 16.22
16-82