Different types of mutations

1. By:
Dr. Sunita Sangwan
Assistant professor, Department of Botany, Govt. College Bhiwani

2.  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

3. 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

4. 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

5. 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

6. 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

7. 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

8. Basis of mutation
classification
Molecular nature
(at DNA)
Point
Mutations
Substitution
Insertion/
deletion
Phenotypic effect (at
proteins)
Silent
Mis-sense
Non-sense
Neutral
Causative agent
(mutagen)
Physical
Temperature
UV rays
Ionizing
raditions
Chemical
Base Analogs
Alkylating
agents
Intercatalating
agents

9. 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

10. GGG AGT GTA GAT CGT
CCC TCA CAT CTA GCA
CCC TCA CAT CTA GCA
GGG AGT GCA GAT CGT A base substitution
CCC TCA CGT CTA GCA
GGG AGT GCA GAT CGT
GGG AGT GTA GAT CGT
CCC TCA CAT CTA GCA
First cycle of DNA replication
Substitution
A base substitution usually leads to base pair
substitution
Mutant DNA Wild DNA

11. Base substitution is of two types:
Transition:
Purine is replaced with a purine
Pyrimidine is replaced with a pyrimidine

12. Transversions:
A purine is replaced by a pyrimidine
or a pyrimidine is replaced by a purine

13. Transition and transversion

16. 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

17. 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.

18. Insertion Mutation
causing frameshift mutation
Normal gene
GGTCTCCTCACGCCA
↓
CCAGAGGAGUGCGGU
Codons
↓
Pro-Glu-Glu-Cys-Gly
Amino acids
Addition mutation
GGTGCTCCTCACGCCA
↓
CCACGAGGAGUGCGGU
↓
Pro-Arg-Gly-Val-Arg

19. Deletion Mutation
causing frameshift mutation
THEBIGCATATETHERAT THEBIGCBATATETHERAT

20. As a result of insertion and deletion of base pairs

21. 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

22. 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
UCA
TTA
AAT
UUA
Ser Leu

23. 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
TGA
ACT
UGA
Ser
Stop codon

24. Silent mutation: alters a codon but due to
degeneracy of the codon, same amino acid
is specified
TCA
AGT
UCA
TCG
AGC
UCG
Ser Ser

25. 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
GAA
CUU
ATT
TAA
AUU
Leu Ile

27. 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

28. Spontaneous Mutations

29. due to tautomeric shift of bases
different tautomeric shifts of bases

30. Tautomeric shifts affect base paring

31. Mutation caused by Tautomeric Shifts

32. Induced Mutations

33. 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

34. 5-bromouracil
an analog of thymine
N
N
1
2
3
6
5
4
O
O
5BU
Br N
N
1
2
3
6
5
4
CH₃
T
O
O

35. N
N
1
2
3
6
5
4
Br
O
5BU
O
N
N
1
2
3
6
5
4
Br
O
5BU
OH
Keto
pairs with A
Enol
mispair with G

38.  Base analogs produce transition
mutations
 Mutations by base analogs can be
reversed by treatment with the same
analog or different analog

39. 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.

40.  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

43. 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

44. 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

47. 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.
Physical mutagens

49. UV radiations
results in dimer formations
and stops the replication

51. Summary of mutations