By:

Dr. Sunita Sangwan

Assistant professor, Department of Botany, Govt. College Bhiwani
  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 line mutations
Some Facts

 Term mutation was given by

Hugo De varies in 1901 while
studying evening
primerose (Oenothera
lamarckiana)
 Most of these were
chromosomal variations
 Some were point variations
Cont.

 Originally the term mutation

was given to both chromosomal
as well as point mutations

 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
 Point mutations
The mutation due to single nucleotide is
known as point mutations.

Mainly divided in to two types :

a) Substitution
b) Insertion and deletion
 Substitution
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 substitution
CGT
CCC TCA CAT CTA GCA
First cycle of DNA replication

GGG AGT GCA GAT

CCC TCA CAT CTA GCA
CGT
GGG AGT GTA GAT
CCC TCA CGT CTA GCA
CGT
Mutant DNA Wild DNA
 Base substitution is of two types:

Transition:
Purine is replaced with a purine

Pyrimidine is replaced with a pyrimidine

Transition and transversion
 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 the mutation
 Also called as frame shift mutations
 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 in-frame

insertions and deletions, respectively.
 Insertion Mutation
causing frameshift mutation

Normal gene Addition mutation

GGTCTCCTCACGCCA GGTGCTCCTCACGCCA
↓ ↓
CCAGAGGAGUGCGGU CCACGAGGAGUGCGGU
Codons
↓ ↓
Pro-Glu-Glu-Cys-Gly Pro-Arg-Gly-Val-Arg
Amino acids
 Deletion Mutation
causing frameshift mutation

THEBIGCATATETHERAT THEBIGCBATATETHERAT
As a result of insertion and deletion of base pairs
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
Missense mutation: a base is substituted that
alters a codon in the mRNA resulting in a
different amino acid in the protein product

TCA TTA
AGT AAT

UCA UUA

Ser Leu
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 TGA
AGT ACT

UCA UGA Stop codon

Ser
Silent mutation: alters a codon but due to
degeneracy of the codon, same amino acid
is specified

TCA TCG
AGT 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 function.
CTT ATT
GAA TAA

CUU AUU

Leu Ile
 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 above the
spontaneous is called a mutagen such as
chemicals & radiations
Spontaneous
Mutations
due to tautomeric shift of bases
different tautomeric shifts of bases
Tautomeric shifts affect base paring
Mutation caused by Tautomeric Shifts
Induced Mutations
 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 newly
synthesized DNA molecules
 5-bromouracil
an analog of thymine

O O

4 4
N 3 5 Br N 3 5 CH₃
5BU T
2 2
6 6
O 1 O 1
N N
 OH
O

4 4
N 3 5 Br N 3 5 Br
5BU 5BU
2 2
6 6
O 1 O 1
N N

Keto Enol
pairs with A mispair with G
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 be
reversed by additional treatment with EMS.
Mustard gas is another alkylating agent.
 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
 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 deletions in replication
 These insertions and deletions frequently
produce frameshift mutations
 Physical mutagens
Radiations:
1. 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 results in
double-strand breaks in DNA.
 UV radiations
results in dimer formations
and stops the replication
Summary of mutations