LECTURE 6 Gene Mutation (Chapter )

LECTURE 6

Gene Mutation

(Chapter 16.1-16.2)

•

Mutation:

A permanent change in the genetic material

that can be passed from parent to offspring.

•

Mutant (genotype):

An organism whose DNA differs

from the wild-type (e.g. GAC becomes GTC)

•

Mutant (phenotype

): An organism whose appearance

differs from the wild-type appearance due to a

mutation (e.g. purple pea flowers become white)

•

Deleterious

: (Adj) Causing harm or damage

INTRODUCTION

• Most mutations are deleterious

– Negative effects, including disease

Mutagen (e.g. UV light)

Gene

INTRODUCTION

• 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

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 (Type 1 and 2 are discussed in lab)

Genome Mutation

Small change in DNA sequence not visible on a karyotype

Gene Mutation



A

Point mutation

is a change of a single base pair

Point Mutations

 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?



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

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

 Beneficial Example: The sickle cell mutation is also beneficial!  Confers resistance to malaria in heterozygotes

 Neutral Example: Over 900 mutations have been documented

 Nonsense mutations change an amino acid coding codon

to a stop codon

 Leads to a truncated polypeptide that is usually non-functional



Additions or deletions

affect short sequences of

DNA

5’ AACAGTCGCTAGATC 3’ 3’ TTGTCAGCGATCTAG 5’

Deletion of four base pairs



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

Effects of Deletions and Insertions

 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

Gene Mutations outside of coding

sequences can affect phenotype

Example: Replication error



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



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 effect

 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

 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



Some mutations are

conditional

 They affect the phenotype only under a defined set

of conditions

 An example is a temperature-sensitive mutation



Mutations can also be divided into the type of cells

affected

 Germ-line cells

 Cells that give rise to gametes such as eggs and sperm

 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  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

Figure 16.4

Therefore, the mutation can be passed on to future

generations

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 cannot be passed on to future generations Germ-line mutation Gametes Embryo Mature individual Mutation is found throughout the entire body. Half of the gametes carry the mutation. Somatic mutation Patch of affected area None of the gametes carry the mutation.

(a) Germ-line 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



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

Spontaneous Mutations

Are Random Events



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"

Random Mutations Can Give an

Organism a Survival Advantage

Figure 16.7 Replica plating

 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

 The Lederbergs' experiment:

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Master plate containing many colonies that were grown in the absence of T1 phage

Velvet cloth

Petri plate with T1 phage

The replica is then gently pressed onto 2 secondary plates that contain 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.

Incubate overnight to allow bacterial growth.

Petri plate with T1 phage