Any sudden change

occurring in hereditary
material is called as
mutation
They may be harmful,
beneficial or neutral

 In multicellular
organism, two broad
categories of mutations:
Somatic mutations &
germ line mutations

Somatic mutations
Arise in the somatic cells
Passed on to other cells through
the process of mitosis
Effect of these mutations depends
on the type of the cell in which they
occur & the developmental stage of
the organism
If occurs early in development,
larger the clone of the mutated cells

Germ line mutations

They occur in the cells
that produce gametes
Passed on to future
generations
In multicellular organisms,
the term mutation is
generally used for germ

Some Facts
Term mutation was given by Hugo
Devries in 1901 while studying
evening
primerose Oenothera lamarckiana
Most of these were chromosomal
variations
Some were point variations
Originally the term mutation was
given to both chromosomal as well
as point mutations

Cont.

Recently chromosomal
mutations are studied
separately
The term mutation is now
given only to point mutations

Definition
DNA is a highly stable
molecule that replicates with
amazing accuracy
Some errors of replication do
occur
A mutation is defined as an
inherited change in genetic
information

Types of gene mutation

Number of ways to classify
gene mutations:
On the basis of the molecular
nature of the defect
On the nature of the
phenotypic effect-- amino
acid sequence of the protein is
altered or not
On the basis of the causative
agent of the mutation

 Base substitution
Insertions & deletions

Base substitution:
Simplest type of gene
mutation
Involves the alteration of
a single
nucleotide in the DNA

A base substitution usually leads to base

pair substitution

GGG AGT GTA GAT

CGT
CCC TCA CAT CTA
GCA
GGG AGT GCA GAT
A base
CGT
CCC TCA CAT CTA substitution
GCA
First cycle of DNA repli
GGG AGT GCA GAT CCC TCA CAT CTA
CGT
GCA
CCC TCA CGT CTA
GGG AGT GTA GAT
GCA
CGT

Base substitution is of two

types:
Transition:
Purine is replaced with a
purine
Pyrimidine is replaced with a
pyrimidine

Insertions & deletions:

2nd major class of gene
mutation
Addition or the removal,
respectively, of one or more
nucleotide pair
Usually changes the reading
frame, altering all amino acids
encoded by codons following

cont.

Additions or deletions in the

multiples of three nucleotides will
lead to addition or deletion of one
or more amino acids
These mutations are called inframe insertions and deletions,
respectively.

Mutations on the basis of the

Phenotypic effects of mutations:
Most common phenotype in
natural populations of the
organism is called as wild type
phenotype
The effect of mutation is
considered with reference to
wild type phenotype

Forward mutation:
a mutation that alters the
wild type phenotype
Reverse mutation (reversion):
a mutation that changes a
mutant
phenotype back in to
the wild type

Missense mutation: a base is

substituted that alters a codon in the
mRNA resulting in a different amino
acid in the protein product
TCA
AGT

TTA
AAT

UCA

UUA

Se
r

Le
u

Nonsense mutation: changes a sense codon

into a nonsense codon. Nonsense mutation
early in the mRNA sequence produces a
greatly shortened & usually nonfunctional
protein
TCA
AGT

UCA

Ser

TGA
ACT

UGA

Stop codo

Silent mutation: alters a codon but

due to degeneracy of the codon, same
amino acid is specified
TCA
AGT

TCG
AGC

UCA

UCG

Ser

Ser

Neutral mutation: mutation that

alters the amino acid sequence of the
protein but does not change its
function as replaced amino acid is
chemically similar or the affected aa
has little influence on protein
CTT
ATT
function. GAA
TAA

CUU

AUU

Leu

Ile

Loss of function mutations:

Complete or partial loss of the normal
function
Structure of protein is so altered that
it no longer works correctly
Mutation can occur in regulatory
region that affects transcription ,
translation or spilicing of the
protein

Gain of function mutations:

Produces an entirely new trait
Causes a trait to appear in
inappropriate tissues or at
inappropriate times in
development
Frequently dominant

Conditional mutations:
Expressed only under certain
conditions
Lethal mutations:
Cause the death of the
organism

Suppressor mutation:
Suppresses the effect of other
mutation
Occurs at a site different from
the site of original mutation
Organism with a suppressor
mutation is a double mutant but
exhibits the phenotype of un
mutated wild type
Different from reverse mutation
in which mutated site is reverted
back into the wild type sequence

On the basis of Causative agent

of mutation:
Spontaneous:
Mutations that result from natural
changes
in DNA
Induced:
Results from changes caused By
environmental chemicals &
radiations
Any environmental agent that
increases the rate of mutation

Chemical Mutagens:
First discovery of a chemical
mutagen was made by
Charlotte Auerbach
Base Analogs:
Chemicals with structures similar
to that of any of the four standard
bases of DNA
DNA polymerases cannot
distinguish these analogs
They may be incorporated into

5-bromouracil
an analog of thymine

N3
2

5BU

6
1

B
r

N3
2

T
6
1

CH

OH

N3

5BU

5
6

N
Keto
pairs
with A

N3

Br

5BU

6
1

Enol
mispair
with G

Br

T
A
5dBU

5dBU

5dBU

G
C
G

TRANISITIO
N
T
C
A
G

3GA5

3 GA 5
C

3GA 5
C
CB
5 G 3

3GA 5
C

CB
5 G 3
Incorporated error

Strand
C
CT
seperation
G
5 3

3GA5
CT
C
CT
5 G 3
5 G 3
replication

3 GA 5
CT
C
5 G 3
5CB 3
G
GG
3 C 5

5 CB 3
G
3GA5
C
CB
5 G 3

3GG5
C
3GG5
C
CCG
5
3

G
C
5dBU

G
5dBU
5dBU
A
A
T

TRANISITI
ON
G
A
C
T

2-amino purine (P)

Base analog of adenine
Normally pairs with
thymine
May mispair with
cytosine
Causes a transition
mutation

T.A

C.G

Incorporated error

3GT5
C
CA
5 G 3

3GT5
C
Strand
separation
CA
5 G 3

3GT5
C
CP
5 G 3
3GT5
C
CA
5 G 3
replication

3GT5
C
CP
5G 3

3GT5
C
CA
5G 3
5CP 3
G
GC
3C 5
5CP 3
G
3GT 5
C
CA
5 G 3

3GC 5
C
3GC 5
C
CG
5G 3

T
A
2AP

T
2AP
C
2AP
C
G

TRANISITI
ON
T
C
A
G

C
G
2AP

C
2AP
T
2AP
T
A

TRANISITION
C
T
G
A

Both base analogs produce

transition mutations
Mutations by base analogs
can be reversed by treatment
with the same analog or
different analog

Alkylating agents:
Chemicals that donate alkyl
groups e.g.
ehylmethanesulfonate(EMS)
It adds an ethyl group to guanine
and produces 6-ethylguanine, which
pairs with thymine and leads to CG:TA
transitions
Also adds an ethyl group to
thymine to produce 4-ethylthymine,
which then pairs with guanine, leading
to a TA:CG transition
Mutations produced by EMS can

C
G

T
A
EMS

EMS

T
6EG

4ET

T
A

C
G

Nitrous acid: causes

deamination
Cytosine
Uracil
NH2

4
N 3

N 3

2
O

6
1
N
H

CYTOSINE

HNO2

2
O

6
1
N
H

URACIL

5
3

C
G 5

HNO2
5
5
3

5U 3

U
G 5

C3
G

5 U 3

3 A 5

3 T 5

C.G

U3
A
5

TA

A
5

Adenine changes into Hypoxanthine which

then pairs with Cytosine
5

A
3T

3
5

HNO2

5
5
3

H
T

3
5

T
A
3

A.T

5H 3

G.C

5 H 3

3 C 5

5 H 3

3 C 5

Guanine changes into Xanthin which pairs with

Cytosine.
Xanthin can also pair with Thymine
5 3

G
3C
5

HNO2

5
5
3

X
C

3
5

G
C
3

G.C

5 X 3

A.T

5 X 3

3 T 5

5 X 3

3 T 5

 Nitrous acid produces

exclusively transition
mutations
Both C.G
T.A & T.A
C.G
transitions are produced
Thus mutations can be
reversed with the nitrous
acid

Hydroxl amine

Specific base modifying mutagen

which adds a hydroxyl group to
cytosine producing hydroxlamine
cytosine which pairs with adenine
instead of guanine
This Leads to C.G
T.A
tranisitions
Acts only on cytosine thus can not
revert the mutation produced

Cytosine changes into hydroxlamine

Cytosine which pairs with Adenine instead
of Guanine
5

C
3G

3
NHOH

5
5
3

hC
G

hC
A

5
hC 3

3
5

C
G
3

C.G

T.A

3 A 5

3 A 5

hC
hC
A

T
5

Oxidative reactions:
Reactive forms of oxygen like
superoxide radicals, hydrogen
peroxide and hdroxyl radicals
produced in the course of normal
aerobic metabolism or by
radiation, ozone, peroxides, and
certain drugs Cause damage to
DNA & induce mutations by
chemical changes
Oxidation converts guanine into

Intercalating agents
Proflavin, acridine orange, ethidium
bromide, and dioxin
They are about the same size as a
nucleotide
They produce mutations by
sandwiching themselves
(intercalating) between adjacent
bases in DNA
They distort the three-dimensional
structure of the helix and cause
single-nucleotide insertions and

Radiations:
Ionizing radiations:
In 1927, Herman Muller demonstrated that
mutations could be induced by X-rays.
X-rays, gamma rays, and cosmic rays are
all capable of penetrating tissues and
damaging DNA.
They remove electrons from the atoms
that they encounter, changing stable
molecules into free radicals and reactive
ions which then alter the structures of
bases and break phosphodiester bonds in
DNA.
Ionizing radiation also frequently

Mutation rates
The frequency with which a gene
changes from the wild type to a
mutant is reffered to as the mutation
rate.
Expressed as the number of
mutations per biological unit i.e.
mutations per cell division, per
gamete per round of replication
e.g. mutation rate for
achondroplasia (hereditary
dwarfism) is about 4 mutations per

Mutation frequency:
Incidence of a specific type of
mutation with in a group of
individual organism
e.g. for achondroplasia, the
mutation frequency in united
states is about 2x10