MUTATIONS

INTRODUCTION

• MUTATION- Any sudden change occurring in hereditary

material is called as mutation.
• They may be harmful, beneficial or neutral.

• DNA is highly stable molecule that replicates with amazing

accuracy
• some errors of replication do occur.
 HISTOR
Y
• 1901: Hugo de Vries first used the term
mutation to describe the sudden heritable
phenotypic changes in evening primrose
Oenothera lamarckiana.
• 1904: T.H. Morgan reported white eyed
drosophila in the population of red eyed
flies.
• 1928: H.J. Muller first used x-rays to induce
mutation in fruit fly.
Thomas Hunt Morgan
TYPES OF MUTATION
GENE MUTATION

• A gene mutation is defined as an alteration in the sequence of

nucleotides in DNA.
• This change can affect a single nucleotide pair or larger gene
segment of a chromosome.
 TYPES OF GENE MUTATION
GENE
MUTATION

Point mutation Frame shift mutation Base substitution

mutation

•Silent mutation
•Insertion •Transition mutation
•Missense mutation
•Deletion •Transversion mutation
•Nonsense mutation
POINT MUTATION
Point mutations are the most common type of gene mutation.

Also known as base pair substitution.

Change in a single nucleotide base pair.

Point mutation can be categorized into three types:

Silent mutation

Missense mutation

Nonsense mutation
SILENT MUTATION
The change in one codon for an
amino acid into another codon
for that same amino acid .
Silent mutations are also
referred to as
mutations. synonymous
MISSENSE MUTATION

The codon for one amino

acid is changed into a codon
for another amino acid.
Missense mutations are
sometimes referred to as
non-synonymous mutations.
NONSENSE MUTATION

The codon for one amino

acid is changed into a
translation termination
(stop) codon.
 FRAME SHIFT MUTATIONS
• This type of mutation occurs when the addition or loss of DNA
bases changes a gene' s reading frame. A reading frame consists
of 3 bases, each code for one amino acid.
• A frame shift mutation shifts the grouping of these bases and
changes the code for amino acids.
• The resulting protein is usually nonfunctional.

Insertions and deletion can all be frame shift mutations.

FRAMESHIFT MUTATIONS
INSERTIO
N
An insertion changes the
number of DNA bases in a
gene by adding a piece of
DNA. As a result, the protein
coded by the gene may not
function properly.
 DELETION
• A deletion changes the
number of DNA bases by
removing a piece of DNA.
•Small deletion may remove
one or few base pairs within
a gene .
•Larger deletions can remove
one entire gene or several
neighboring genes. The
deleted DNA may alter the
function of the resulting
protein.
 BASE SUBSTITUTION
MUTATION
Base substitution are mutation in which one base pair is
replaced by another.

Base substitutions can be divide into two subtype

transition mutation

transversion mutation
TRANSITION MUTATION

A transition is the replacement of a

base by the other base of the same
chemical.
TRANSVERSION MUTATION

A transversion is the opposite

the replacement of a base of
one chemical category by a
base of the other.
All mutations result in the production of a mutant.
a) True
b) False

Which of the following is not a point mutation?

a) Substitution
b) Transposition
c) Insertion
d) Transversion
A frame shift mutation will have minimum effect when it leads to ______________
a) Insertion of 2 bases
b) Deletion of 1 base
c) Insertion of 3 bases
d) Deletion of 2 bases
MOLECULAR MECHANISM OF
MUTATION
• Spontaneous mutation
 Tautomerism
 Depurination
 Deamination
• Induced mutation
 Physical mutagens
Radiation
a. Ionizing
b. Non ionizing
 Heat
 Chemical mutagens
Base analogs, alkylating agent, intercalating agent
SPONTANEOUS MUTATION

Spontaneous mutation are those which arise naturally, not

through the action of a mutagenic agent, they may arise through
-
Errors in DNA replication

Spontaneous alteration of anucleotide within an existing DNA molecule.

SPONTANEOUS MUTATION
• Tautomerism- A base is changed by the
repositioning of a hydrogen atom, altering the
hydrogen bonding pattern of that bases, resulting
in an incorrect base pairing replication.

• Depurination- Loss of purine base (A or G) to

form an apurinic site.

• Deamination- Hydrolysis changes a normal base

to an a typical base containing a keto group in
place of the original amino acid.
 INDUCED MUTATION

◦ During its lifetime, an organism may be exposed to a variety of physical, chemical, and biological agents capable of
causing damage to its genetic material

Physical mutagens
Radiation
a. Ionizing (e.g. X-ray, gamma ray, cosmic ray)
b. Non ionizing (e.g. UV ray)
Heat
a. Break the N-glycosidic bond in DNA
b. Result form apurinic site or base less site
 Chemical mutagens
a. Base analogs
b. Alkylating agent
c. Intercalating agent
Physical Mutagens

Radiation was the first mutagenic

agent known; its effects on genes
were first reported in the 1920's.

Radiations are of two types.

I. EM radiations

II. Ionizing radiations

 Physical Mutagen
 1.Electromagnetic Radiations (Non ionizing): Visible light and
other forms of radiation are all types of electromagnetic radiation
(consists of electric and magnetic waves).
The portion of light which is biologically significant is UV and higher
energy radiation.
UV radiation is not ionizing but can react with DNA and other biological
molecules
UV radiation: Cyclobutane pyrimidine dimers, Thymidine dimers (T-T)
Physical Mutagen
 Physical Mutagen
 2. Ionizing Radiatons:
◦ X- and gamma-rays.
◦ Produce reactive ions (charged atoms or molecules) which react with biological molecules.
◦ Damage base and sugar residues.
◦ This term also includes corpuscular radiation-
• streams of atomic and subatomic particles emitted by radioactive elements:
• these are of two types, alpha- and beta-particles
Physical Mutagen
The rapidly dividing cell types (blood cell-forming areas of bone
marrow, gastrointestinal tract lining) are the most affected by ionizing
radiation.
The severity of the effects depends upon the dose received.
Ionizing radiation produces a range of effects on DNA both through
free radical effects and direct action:
-breaks in one or both
-damage to/loss of bases (mutations)
-crosslinking of DNA to itself or proteins
Chemical Mutagens
The first report of mutagenic action of a chemical
was in 1942.
There are many hundreds of known chemical
mutagens.
Chemical mutagens are categorized into four
general groups, based on the mechanism by which
they interact with DNA.
1.Base analogs
2.Base altering chemicals
3.Intercalating agents
4.Agents altering DNA structures
Chemical Mutagens

 1.Base analogs:
These chemicals structurally resemble
purines and pyrimidines and may be
incorporated into DNA in place of the
normal bases during DNA replication:

 bromouracil (BU)--artificially created

compound extensively used in research.

 Resembles thymine (has Br atom instead

of methyl group) and will be incorporated
into DNA and pair with A like thymine. It
has a higher likelihood for tautomerization
to the enol form (BU*)
Chemical Mutagens
Chemical Mutagens
 2.Chemicals which alter structure and pairing properties of
bases:
It includes:
• hydroxylating agent (add OH-group to C)
• alkylating agent such as EMS (ethylmethane sulfonate);

chemical mutagens that react with bases and add methyl or ethyl groups
• deaminating agent such as nitrous acid; -formed by digestion of nitrites
(preservatives) in foods. It causes C to U, C to T, and A to hypoxanthine
deaminations. Deamination by nitrous acid, causes transitions.
Chemical Mutagens
 3.Intercalating agents
acridine orange, proflavin, ethidium bromide
All are flat, multiple ring molecules which interact with bases of DNA and
insert between them.
This insertion causes a "stretching" of the DNA duplex and the DNA
polymerase is "fooled" into inserting an extra base opposite an
intercalated molecule.
The result is that intercalating agents cause frameshifts.
Chemical Mutagens
Chemical Mutagens
 4.Agents altering DNA structure
This is a "catch-all" category which includes a variety of different kinds
of agents. These may be:
• --large molecules which bind to bases in DNA and cause them to be
noncoding--referred as "bulky" lesions.
• --agents causing intra- and inter-strand crosslinks (eg. psoralens--
found in some vegetables and used in treatments of some skin
conditions)
• --chemicals causing DNA strand breaks (eg. peroxides)
 EFFECTS OF GENE MUTATION
Effects

Beneficial Harmful Neutral

•Produce new version of •Protein malfunction

protein
•Lethal to life
•Essential for evolution
•Not significantly harm or
•Sometimes stops the benefit body
•Enhance the survival development of fetus.
and reproductive success
•Cause genetic disorder
•Turn off harmful genes
 GENETIC DISORDER
• Mutation can lead to missing or malformed
proteins that can lead to diseases.
• Some well known inherited genetic disorders

Sickle cell anemia, Cancer

• All these disorders are caused by the

mutation of a single gene.

Which base undergoes spontaneous damage under physiological conditions?
a) Thymine
b) Cytosine
c) Uracil
d) Guanine

Which base is generated due to the deamination of adenine?

a) Guanine
b) Cytosine
c) Uracil
d) Hypoxanthine
Which base is generated by the deamination of guanine?
a) Xanthine
b) Cytosine
c) Hypoxanthine
d) Thymine

In the following compound which is one of the intercalating agents?

a) Ethidium
b) 5-bromouracil
c) Purine
d) Clastrogen
 Mutation rates and mutation frequencies are terms describing the quantitative
measure of the occurrence of mutations

 Mutation rate presents the probability of a particular kind of mutation as a function of

time

 i.e. number per nucleotide pair per generation or per gene per generation ex:
spontaneous mutation rate in Eukaryote is 10-4 to 10-6 per gene/generation
 Mutation frequency is the number of occurrences of a
particular kind of mutation expressed as the proportion of
cells or individuals in a population i.e. the number per
100,000 organisms or number per 1 million gametes