Download Brooker Chapter 16

LECTURE 6
Gene Mutation
(Chapter 16.1-16.2)
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• Deleterious: (Adj) Causing harm or damage
• Truncated: (Adj) Cut short
• Restriction: The state of being limited in purpose or
capacity
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INTRODUCTION
• Mutation = heritable change to DNA
– Wild type allele → mutant allele
– Creates an unusual allele
– If it occurs with a gene, it is usually deleterious
• On the positive side, mutations are the
foundation for evolutionary change
• On the negative side, mutations are much
more likely to be harmful than beneficial to
the individual and often are the cause of
diseases
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Mutagen (e.g. UV light)
Gene
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16.1 CONSEQUENCES OF
MUTATIONS
• Mutations can be divided into three main types
– 1. Chromosome mutations
• Changes in chromosome structure
– 2. Genome mutations
• Changes in chromosome number
– 3. Gene mutations
• Relatively small change in DNA structure that affects a single
gene
– Type 3 will be discussed in this chapter
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Genome Mutation
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Chromosomal Mutation
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Gene Mutation
Small
change
in DNA
sequenc
e not
visible
on a
karyoty
pe
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Point Mutations

A Point mutation is a change of a single base pair
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
Is the above change a transition or a transversion?
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Effects of Point Mutations

Point mutations in the coding sequence of a
structural gene can have various effects on the
polypeptide

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
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Effects of Point Mutations


Missense mutations change the amino acid coded by the
codon
May be deleterious, beneficial, or neutral

Deleterious example: Sickle-cell anemia Glu →Val
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
Beneficial Example: The sickle cell mutation is also beneficial!

Confers resistance to malaria in heterozygotes
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
Neutral Example: Over 900 mutations have been documented
in CFTR gene; many have no phenotypic effect
Cystic fibrosis
(severe)
Cystic fibrosis
(mild)
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
Nonsense mutations change an amino acid coding codon
to a stop codon

Leads to a truncated polypeptide that is usually non-functional
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
Additions or deletions affect short sequences of
DNA
5’ AACGCTAGATC 3’
3’ TTGCGATCTAG 5’
5’ AACGCTC 3’
3’ TTGCGAG 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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Effects of Deletions and Insertions

Deletions and insertions can be divided into


Those that cause reading frame shifts
 Number of base-pairs deleted or inserted is not
divisible by 3 (e.g. 1, 2, 4, 5…)
 Usually result in a truncated non-functional
polypeptide with a deleterious phenotype
 But can also be neutral of even beneficial
Those that don’t cause reading frame shifts
 Number of base-pairs deleted or inserted is divisible
by 3 (e.g. 3, 6, 9, 12…)
 Usually less harmful than reading frame shift
mutations
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
Beneficial Example: Mutation in CD4 receptor on lymphocytes
32 bp deletion results in a reading frame shift;
receptor non-functional; prevents HIV virus
entry into the cell
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Gene Mutations outside of coding
sequences can affect phenotype


Mutations in the core promoter can change levels of gene
expression
 Up mutations increase expression. Down mutations
decrease expression
Other important non-coding mutations are in Table 16.2
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Example: Replication error
FIRST
SECOND
OPPORTUNITY OPPORTUNITY
FOR DNA
FOR DNA
REPAIR
REPAIR
MUTATION IS
NOW “FIXED”
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Other ways to Categorize Mutations

In a natural population, the wild-type is the relatively
prevalent genotype. Genes with multiple alleles may
have two or more wild-types (variations).

A forward mutation changes the wild-type genotype
into some new variation

A reverse mutation changes a mutant allele back to
the wild-type

It is also termed a reversion
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

Mutations can also be described based on their
effects on the wild-type phenotype
As we’ve seen, they are often characterized by
their phenotypic eddect

Deleterious mutations decrease the chances of survival




The most extreme are lethal mutations
Beneficial mutations enhance the survival or reproductive
success of an organism
The environment can affect whether a given mutation is
deleterious or beneficial
Some mutations are conditional


They affect the phenotype only under a defined set of
conditions
An example is a temperature-sensitive mutation
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
Mutations can also be divided into the type of cells
affected

Germ-line cells


Somatic cells


All other cells
Germ-line mutations are those that occur directly in a
sperm or egg cell, or in one of their precursor cells


Cells that give rise to gametes such as eggs and sperm
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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Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Germ-line
mutation
Gametes
Embryo
Somatic
mutation
The size of the patch
will depend on the
timing of the mutation
The earlier the mutation,
the larger the patch
Therefore, the
mutation can
be passed on
to future
generations
Mutation is
found
throughout
the entire
body.
Half of
the gametes
carry the
mutation.
Figure 16.4
(a) Germ-line mutation
An individual who has
somatic regions
that are
genotypically
different from each
other is called a
genetic mosaic
Therefore, the mutation cannot be
passed on to future
generations
Patch of
affected
area
Mature
individual
None of
the gametes
carry the
mutation.
(b) Somatic cell mutation
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16.2 OCCURRENCE AND CAUSES
OF MUTATION
• Mutations can occur spontaneously or be induced
• Spontaneous mutations
– Result from abnormalities in cellular/biological processes
• Errors in DNA replication, for example
– Underlying cause originates within the cell
• Induced mutations
– Caused by environmental agents
– Agents that are known to alter DNA structure are termed
mutagens
• These can be chemical or physical agents
• Refer to Table 16.4
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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: Physiological adaptation theory


Proposed that physiological events (e.g. use and disuse)
determine whether traits are passed along to offspring
Charles Darwin: Random mutation theory

Proposed that genetic variation occurs by chance

Natural selection results in better-adapted organisms
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Random Mutations Can Give an
Organism a Survival Advantage


Joshua and Ester Lederberg(1950s) devised an
ingenious way to test these alterative theories
experimentally
Studied the resistance of E. coli to infection by
bacteriophage T1



tonr (T one resistance)
Hypothesis: E. coli cells that survive T1 infection were
already resistant to the phage prior to exposure
 Due to random mutations
"Replica plating"
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The Lederbergs'
experiment:
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
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Master plate containing
many colonies that were
grown in the absence of
T1 phage
A velvet cloth (wrapped over a
cylinder) is pressed gently onto the
master plate and then lifted. A little
bit of each bacterial colony adheres
to the velvet cloth, thereby creating
a replica of the arrangement of
colonies on the master plate.
Velvet cloth
The replica is then gently pressed
onto 2 secondary plates that
contain T1 phage.
Petri plate
with T1 phage
Petri plate
with T1 phage
Incubate overnight to
allow bacterial growth.
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