The document discusses mutations, which are changes in genetic material that can lead to heritable characteristics. It categorizes mutations based on their occurrence (somatic and germinal), mode (spontaneous and induced), and nature (chromosomal and gene mutations), detailing their mechanisms and effects. Various mutagens, including physical and chemical agents, as well as specific types of mutations like silent, missense, and nonsense mutations, are described to illustrate their significance in genetic variability and the development of diseases.

1. Dr.Saji Mariam George
Associate Professor (Retired)
Assumption College Autonomous
Changanacherry
MUTATIONS

2. MUTATIONS
• Hugo de Vries (1901) introduced the term mutation to
describe the sudden appearance of heritable
characteristics based on his observations on the
evening primrose, Oenothera lamarckiana.
• Mutation is the change in the genetic material.
[Deoxyribonucleic acid, (DNA) - in most of the
organisms, Ribonucleic acid (RNA) in some viruses].
• The organism subjected to a mutation is called a
mutant.
• Mutations can result in a new allele.

3. Hugo de Vries Evening primrose, Oenothera
lamarckiana
http://evolutionlist.blogspot.com

4. A mutation may be
• Lethal – results in the premature death of the
organism.
• Semilethal – causing the death of more than 50%, but
not of all individuals of mutant genotype.
• Sub vital – lowers viability, but causes the death of
less than 50% of mutants.
• Supervital – increases the viability of individuals
bearing it above the wild type allele.

5. Types of Mutations
Mutations can be classified into different types based on different
criteria.
1. Based on the site of occurrence, mutations are of
two types.
i) Somatic mutations
• Occur in somatic (Gr. Soma = body) cells(non-germline cells) –
Somatic mutations may lead to somatic mosaicism - a condition
in which somatic or body cells of an individual may have
different genetic constitution(genotype).
• Non- heritable – not transmitted to the next generation in
sexually reproducing organisms. But in plants having asexual
reproduction methods, somatic mutations can be transmitted
to the next generation by the corresponding vegetative
propagation method.
• Somatic mutations are also involved in the development of
many human cancers, neuropsychyatric diseases etc.

6. Somatic mutation – Variegated leaves
https://www.reddit.com

7. Somatic mutation in Lettuce leaves
A somatic mutation disrupted the accumulation of green chlorophyll
pigment resulting white patch
Kathryn Barton
http://vanishingbananas.blogspot.com/2013/01/mutants-we-eat-sectors-and-somatic.html

8. Somatic mutation in Tulip
Somatic mutation in yellow Tulip has caused two of the petals to turn red.
https://ag.purdue.edu

9. Somatic mutation-Normal parent with puppy showing
somatic mutation for coat color
https://biologywise.com

10. ii) Germinal mutations (Germline mutations)
• Mutations that occur in germ cells (reproductive
cells) are called Germinal mutations (Germline
mutations)- occur in the female gamete (egg) or
male gamete (sperm) – heritable – transmitted to
the next generation.

11. 2. Based on the mode of occurrence, mutations are of
two types.
i) Spontaneous (Background ) mutations
• Mutations that occur spontaneously in natural
populations at a low rate.
• It may be due to errors in DNA replication or due to
cosmic rays or the emissions from radioactive decay of
unstable isotopes of elements like Uranium, Thorium
etc.

12. https://www.graincentral.com/cropping/spontaneous-mutation-and-its-implications-
for-herbicide-resistance

13. ii) Induced mutations
• Mutations can be induced with the help of
certain agents known as mutagens .
• Induced mutations are widely used in crop
improvement programs – Mutation Breeding.

14. Types of Mutagens
a) Physical mutagens
b) Chemical mutagens

15. a) Physical mutagens
Include
• High energy, ionizing radiations
• They can cause ionisation when interact with
matter.
• Include particulate radiations such as alpha
particles(alpha rays, α-rays) beta particles (beta
rays, β -rays ), fast neutrons (free neutrons with
high energy, released by nuclear fission),
thermal neutrons (produced by slowing down
more energetic neutrons in a substance called a
moderator after they have been ejected from
atomic nuclei during nuclear fission) etc.

16. • Non-particulate (electromagnetic) radiations
include X-rays and Gamma rays (γ- rays).
• Gamma rays are the most commonly used Physical
mutagen in a Mutation breeding program.
• High energy , ionising radiations may cause
deamination of bases, deletion of a base, breaking
of Hydrogen bonds in DNA, single and double
strand breaks in DNA etc.

17. • Low energy , non-ionizing radiation
• Ultraviolet radiation(UV) – causes dimers of
Thymine, Uracil and sometimes Cytosine present
in the same strand of DNA.
• It also promotes deamination of Cytosine.
• The most effective wavelength of UV is 2540 Å
since DNA bases show the maximum absorption
at this wavelength.
• Poor penetration capacity.
• Useful for irradiation of pollen grains and
unicellular organisms.

18. b) Chemical mutagens
• Chemicals which induce mutations.
• e.g. Sulphur mustard(Mustard gas, the first
chemical shown to be mutagenic by Charlotte
Auerbach et. al.,) Nitrogen mustard, Ethyl
Methane Sulphonate (EMS), Methyl Methane
Sulphonate (MMS), 5 – Bromouracil, Acridine dyes
like Acriflavine, Proflavine, Acridine orange etc.
• The mechanism of action varies to a great extent
from one group of chemical mutagens to another.

19. The chemical mutagens may cause changes in DNA
which include
• Mistakes in base pairing during DNA replication
• Deletion
• Insertion or substitution of a base
• Single or double strand breaks
• Changes in hydrogen bonding properties of
bases .
• Inactivation of DNA by preventing replication
etc.

20. Chemical mutagens based on mode of
action
i). Base analogues
• Their structure is similar to that of a naturally
occurring base so that they are incorporated
into DNA during replication, instead of a
normal base.
e.g. : 5 – Bromouracil (5 BU), 2 –Aminopurine .

21. • 5 - Bromouracil (5BU) or its nucleoside 5 –
bromodeoxyuridine (BrdU, BUdR, BUDR, BRDU )
in its usual keto form is structurally similar to
the nitrogen base Thymine.
• So, it may be incorporated instead of the
normal base Thymine so that an A – T pair
becomes A – BU.
• If it undergoes a tautomeric shift to its less
stable enol form during a subsequent
replication, 5 – Bromouracil pairs with Guanine.
Thus it will cause an A : T to G : C transition.

22. • When 5 – Bromouracil is present in its less
frequent enol form at the time of incorporation
into DNA, it pairs with Guanine.
• When it undergoes a tautomeric shift back to its
more stable keto form, 5 - Bromouracil pairs
with Adenine and cause a G : C to A : T
transition.
Thus , 5 - Bromouracil induces transitions in
both directions A : T & G : C .

23. ii). Agents modifying Purines and Pyrimidines
 Alkylating agents
 Nitrous acid (HNO2)
 Hydroxyl amine (NH2OH)

24. a) Alkylating agents
• Most widely used mutagens that react with purines.
• Have direct mutagenic effect on DNA.
• One mechanism of mutagenesis by alkylating
agents involves the transfer of methyl or ethyl
groups to the bases resulting in altered base pairing
potentials.
e.g : Ethyl Methane Sulphonate (EMS) , Diethyl
Sulphonate (DES), Methyl Methane Sulphonate
(MMS) , Nitrogen mustard, Sulphur mustard etc.

25. • Most commonly used alkylating agent is Ethyl
Methane Sulphonate (EMS).
• It causes the alkylation of Guanine (addition of
an ethyl group to the number 7 Nitrogen) which
allows it to pair with Thymine.
• Then during replication, the complementary
strand receives Thymine instead of Cytosine.
Thus it causes G: C to A : T transition.
• Thus EMS causes base substitutions of the
transition type.

26. b) Nitrous acid (HNO2)
• It causes deamination of Adenine which
results in the formation of Hypoxanthine.
• The pairing behaviour of Hypoxanthine is like
that of Guanine.
• Therefore Hypoxanthine may pair with
Cytosine so that A – T pairing is replaced by
G – C pairing.

27. c) Hydroxyl amine (NH2OH)
• Deaminates Cytosine to a base which pairs
with Adenine instead of Guanine.
• Thus C – G pairing is changed to A - T pairing.

28. iii). Agents producing distortions in DNA
• Fluorescent Acridine dyes – Proflavine,
Acridine orange etc. cause mutations by
insertion or deletion of bases that induce
frameshift mutations.
• The positively charged Acridine intercalate
between DNA and increase the rigidity and
alter the conformation of the double helix
causing slight bend in the DNA molecule
causing distortions in the DNA.

29. • When DNA molecule containing intercalated
Acridine replicate, additions and deletions ,
usually of a single base pair result which in
turn alter the reading frame of the portion of
the gene distal to the mutation.
• Thus Acridine – induced mutations in exons
of genes usually results in non – functional
gene products.

30. 3. Based on the way, the genetic material is changed
, mutations are of two types.
i) Chromosomal mutations
a) Heritable change in the number of chromosomes
• Monoploidy (Haploidy) - have only one set of
chromosomes.
• Euploidy ( Polyploidy) - have more than two sets
of chromosomes - Polyploid organisms may have
three (3x), four(4x) or more sets of chromosomes
-Polyploidy results in the fixation of heterozygous
gene combinations, particularly those derived by
hybridization.

31. • Aneuploidy - loss or gain of one or a few chromosomes -
hyperploidy (an excess of chromosomes)- hypoploidy
(one or more chromosomes are lacking).
Aneuploid variations in chromosome number include
• Monosomy - loss of one member of a pair of
chromosomes , 2n – 1.
• Double Monosomy - loss of two non-homologous
chromosomes, 2n -1-1 .
• Nullisomy - loss of a homologous pair , 2n – 2.

32. • Trisomy - addition of a third homologue to a pair or
three copies of a particular chromosome,
2n + 1.
• Double Trisomy - two different chromosomes are
present in triplicate and has the genomic formula , 2n
+ 1 + 1.
• Tetrasomy - addition of two homologues to a pair or
four copies of a particular chromosome , 2n + 2.
• Double Tetrasomy - addition of two homologues to a
pair and two homologues to another pair, 2n + 2 + 2.

33. b) Heritable change in the structure of chromosomes.
• Deletion - loss of a a few genes or a segment of a
chromosome.
• Duplication – Addition of a few genes or a segment of
a chromosome.
• Inversion – Two breaks in a chromosome and the
broken segment is reinserted after a rotation of 180° .
• Translocation- a broken segment of the chromosome
may be translocated to the same chromosome or to a
different chromosome.

34. • Chromosomal mutations have a significant
role in instantaneous speciation.
• Chromosomal rearrangements in most cases
do not produce new species – this leads to
chromosomal polymorphism – only in a few
cases, this produces speciation.

35. ii) Gene mutations (Point mutations)
• Alterations of single genes.
• Genes are not stable - may undergo changes
- altered sequence of nucleotides - mutations
to a different allele.
• Results in a change in the protein that the
gene codes for.
• Muton – the unit of mutation.
• Gene mutations are the source of genetic
variability.

36. Types of Gene mutations
i) Silent mutations
• Alterations in the DNA molecule that does
not produce any amino acid change in the
protein synthesized.
• They change a nucleotide but not the amino
acid sequence because they affect the third
position of the codon, which is usually less
important in coding.

37. Let us consider an imaginary m RNA
3 6 9 12 15 18
AUG UAU CCA UAU CCA UAG
fMet Tyr Pro Tyr Pro Term
fMet- Nformyl methionine - a derivative of the amino acid Methionine in
which a formyl group has been added to the amino group. It is specifically
used for the initiation of protein synthesis.
Tyr – Tyrosine (An amino acid)
Pro- Proline (An amino acid)
Term- Termination codon
An A to U change in position 9 will give
AUG UAU CCU UAU CCA UAG
fMet Tyr Pro Tyr Pro Term.
This is a Silent mutation because it leaves the amino acid sequence
unchanged.

38. ii) Missense Mutations
• This is a mutation that changes a codon coding for one
amino acid to a codon coding for another amino acid.
3 6 9 12 15 18
AUG UAU CCA UAU CCA UAG
fMet Tyr Pro Tyr Pro Term
Here, a C to U change at position 7 will give a different
amino acid.
3 6 9 12 15 18
AUG UAU UCA UAU CCA UAG
fMet Tyr Ser Tyr Pro Term
Ser- Serine (An amino acid)

39. Example :
• Sickle cell anemia in man is due
to the change of the amino acid
Glutamic acid to Valine .
• In the Beta chain of normal
haemoglobin A, the sixth amino
acid is Glutamic acid coded by
the nucleotide sequence
GAA or GAG in the DNA.
• In the Heamoglobin S of
patients with Sickle cell anemia,
the amino acid in the
corresponding position of Beta
chain is Valine coded by
GTA or GTG. Here A is replaced
by T.

40. A sickle-shaped red blood cell among a group of normal red blood cells.
Creative Commons EM Unit, UCL Medical School, Royal Free Campus,
https://www.nature.com/scitable/topicpage/genetic-mutation-441/

41. iii) Nonsense mutations
A mutation that converts a codon that specify a particular
amino acid into one that does not code any amino acid, a
nonsense codon or stop codons or termination codons –
UAG (Amber) , UGA (Opal or Umber) and UAA (Ochre) .
3 6 9 12 15 18
AUG UAU CCA UAU CCA UAG
fMet Tyr Pro Tyr Pro Term
Here, a U to G change at position 12 will give
3 6 9 12
AUG UAU CCA UAG
fMet Tyr Pro Term
Here, a codon for an amino acid is mutated into a
termination codon – UAG, which stops protein synthesis.

42. iv) Frame shift mutations
• Arise from the insertion or deletions in the DNA molecule which
shift the normal reading frame for translation, often leading to
non-functional protein products.
3 6 9 12 15 18
AUG UAU G CCA UAU CCA UAG
fMet Tyr Pro Tyr Pro Term
Here, an insertion of an extra G between nucleotides 6 and 7 – alters
the reading frame for translation.
3 6 9 12 15 18
AUG UAU GCC AUA UCC AUA
fMet Tyr Ala Ile Ser Ile
Ala- Alanine (An amino acid)
Ile- Isoleucine (An amino acid)

43. Molecular mechanism of mutations
Tautomeric shifts
• The structures of bases in the DNA are not
static.
• Hydrogen atoms can move from one position
in a purine or pyrimidine to another position
- from an amino group to a ring Nitrogen.
• Such chemical fluctuations – Tautomeric
shifts - Rare .

44. • Rarely, the more stable keto forms of
Thymine and Guanine & the amino forms
of Adenine and Cytosine may undergo
tautomeric shifts to less stable enol and
imino forms respectively.
• The bases would exist in their less stable
tautomeric forms only for a short period.
• But, if a base existed in the rare form at the
moment that it was being replicated or being
incorporated into a nascent DNA chain, a
mutation would result.

45. • When the bases are present in their rare imino
or enol states, they can form Adenine – Cytosine
and Guanine – Thymine base pairs.
• The net effect of such an event, and the
subsequent replication required to segregate the
mismatched base pair , is an A : T to G : C or a
G : C to A : T base pair substitution.

46. Tautomeric forms
of the 4 common
bases in the DNA
The shifts of
Hydrogen atoms
between the
number 3 and
number 4
positions of the
Pyrimidines and
between the
number 1 and
number 6
positions of the
Purines change
their base –
pairing potential.

47. Base pair substitutions
• Most common mutations
• Result in the incorporation of wrong bases during
replication or repair of DNA.
Types
i)Transition : One purine is substituted by another
purine
or
one pyrimidine is substituted by another pyrimidine.
ii) Transversion : One purine is substituted by another
pyrimidine or vice versa.
(Purines- nitrogen bases Adenine and Guanine
Pyrimidines – Nitrogen bases Thymine (in DNA), Uracil
(instead of Thymine in RNA) and Cytosine.

48. Transposable elements (Transposons,
Jumping genes) – have mutagenic effects.
• A DNA sequence that can move or “jump”
themselves around the genome and hence the name
jumping genes. They can create or reverse mutations.
• The insertion of a transposon into a gene will may
render the gene nonfunctional. If the gene encodes
an important product, a mutant phenotype may be
produced.
• Insertion of transposable genetic elements into
important genes resulted in the production of many
mutants in Maize.

49. Barbara Mc Clintock - Discoverer of Jumping genes in Maize,
Zea mays (1940’s), which produce variously coloured kernels.
(Awarded the Nobel Prize in 1983).
https://www.sciencephoto.com/media/890826/view/us-geneticist-barbara-
mcclintock-in-maize-field-1960s

50. Maize kernels show high variations in colour due to an
interplay between a transposable element and a pigment gene.
Source: Damon Lisch
https://www.hopkinsmedicine.org/research/advancements-in-research/fundamentals/in-
depth/jumping-genes-and-cancer

52. Variations in kernel colour in Maize
(Zea mays)
https://www.canr.msu.edu/news/mutants-have-value-too

53. Paramutation
• Discovered by Brink (1950) in Corn (Zea mays )
– a heritable change in gene expression induced
by allele interactions.
• The change may be in the pattern of DNA
methylation or histone modifications.
• One allele influences the expression of another
allele at the same locus when the two are
combined in a heterozygote.
• The first allele is referred to as “paramutagenic”
and the second as “paramutable (paramutant)”.
• This change is inheritable.

54. • Paramutation - First observed by the effect it
had on the colour of corn kernel.
• A paramutant allele has different levels of gene
expression. So the offsprings with the same
genetic sequence may have drastically different
phenotypes.
• For example, the alleles of the red 1 (r 1) locus in
maize encodes a transcription factor that gives
red pigment to corn kernels.

55. • The expression of a paramutant allele may
cause variation in the colour of kernels
ranging from completely colourless to fully
coloured kernels.
• The weaker expression may result in different
light shades to corn kernels.
• Paramutation of the r1 Locus of Maize is
associated with increased Cytosine
methylation.

56. Paramutation at the Maize p1 (pericarp color1) gene is associated with
transcriptional silencing and is observed as patterned pericarp (seed coat)
pigmentation (front ear).
https://www.genetics.org
Lyudmila Sidorenko and Vicki Chandler
GENETICS December 1, 2008 vol. 180 no. 4 1983-1993

57. • Any change in the genetic material alters the
gene pool and the character of the
organisms.
• Mutations are the ultimate source of all
genetic variations and provide the genetic
variability that allow the organisms to evolve
and adapt to new environment.

58. THANK YOU