This document discusses mutagens and types of mutations. It defines mutagens as physical, chemical, or biological agents that cause mutations by altering genes or gene expression. It describes several types of mutagens including radiation, chemicals, viruses and bacteria. It also categorizes different types of mutations including point mutations, frameshift mutations, transitions, transversions, missense mutations and more. Several examples of diseases caused by specific mutations are provided such as sickle cell anemia, cystic fibrosis, and others.

1. MUTAGENS & TYPES OF
MUTATIONS
PRESENTED BY:
MOUSAMI JARIA
ST. GEORGE COLLEGE OF MANAGEMENT AND
SCIENCE
MSC MICROBIOLOGY
SEMESTER - 2

2. INTRODUCTION
 Mutagens are the known agents either physical,
chemical or biological cause mutations by altering
the genotype or gene expression which results in
genetic abnormality.
 Not all mutations are caused by mutagens only
induced mutations were caused by mutagens.
Spontaneous mutations are naturally occuring
mutations.
 Mutagens causing cancer, are likely to be known as
carcinogens.

3. DISCOVERY
 The first mutagens to be identified were
carcinogens.
 The mutagenic property of mutagens was first
demonstrated in1927 by Muller , he discovered
that X-rays can cause genetic mutations in fruit
flies.
 Edger Altenburg also demonstrated the
mutational effect of UV radiation in 1928.
 Charlotte Auerbach and J.M Robson found that
mustard gas can cause mutations in fruit flies.

4. EFFECTS
 At chromosomal level mutagens alter the structure or
number of chromosomes, as deletion, duplication,
insertion, translocation, monosomy and
nondisjunction are some of the chromosomal
abnormalities caused by mutagens.
 Teratogens are class of the mutagens which causes
congenital malformations. Eg: X-rays, valporate,
toxoplasma.
 Carcinognes are the class of mutagens which
induces tumour formation and thus cause cancer.

5. Carcinogenic agents include X-rays/ UV rays,
aflatoxins, retrovirus etc.
 Clastogens are the class of mutagens responsible
for chromosomal –breakage, deletion, duplication
and rearrangements. UV rays, bleomycins, HIV
virus are common type of clastogens.
 Mutagens also alters the codon, deletes bases, alters
bases, breaks hydrogen bonds, phosphodiester
bonds or changes gene expression.

7. TYPES OF MUTAGENS
 Three different types of common mutations are
observed in nature physical, chemical & biological
agents.
 Many mutagens are not mutagenic by themselves ,
but can form mutagenic metabolites through cellular
process. Such mutagens are called promutagens.
 Physical agents:
o Heat and radiation
 Chemical agents:
oBase anlogues

8. oIntercalating agents
oAlkylating agents
oDeaminating agents
oMetal ions
 Biological agents:
oViruses
oBacteria
oTransposons.

10. PHYSICAL MUTAGENS
 RADIATION:
i. The first mutagenic agent reported in1920.
ii. Radiations directly damage the DNA or nucleotide
structure which might be either lethal or sub lethal
iii. Radiation causes cross linking of DNA or protein,
chromosomal break, stand break or loss of
chromosomes.
iv. At the molecular level it causes deletion of bases or
DNA strand bases.

11. a. X-RAY RADIATION:
o X-rays are one of the most common types of
ionizing radiation used in many of the medical
practices.
o At molecular level the lethal dose of X-ray (350-
500rems) breaks phosphodiester bonds between
DNA and thus results in strands breakage.
o It causes multiple strand breakage.
o If strand breakage occurs in both the strands , it
becomes lethal for cell.

12. b. UV- rays:
o It is non ionizing type of radiation having less energy
in it.
o The major causes of UV radiation are base deletion
,strand breakage, cross linking and generation of
nucleotide dimers.
o UV induced mutations are dimer formation, thymine-
thymine dimer & thymine-cytosine dimers are
commonly formed as the lesions block replication as
well as transcription.
o Formation of pyrimidine dimerization cause
distortion in structure of DNA and prevents
formation of replication fork.

14. CHEMICAL MUTAGENS
 BASE ANALOGS:
o They are similar to the bases of DNA-purine and
pyrimidines or structurally resemble the DNA bases.
o Bromouracil and aminopurine are two common base
analogs incorporated in DNA instead of normal
bases.
o Bromouracil pairs with adenine as like the thymine
and causes mutation .
o Aminopurines cause AT to GC or GC to AT transition
during replication.

16.  ALKYLATING AGENTS:
o Ethylnitrosourea, mustard gas and vinyl chloride are
common alkylating agents, add alkyl group to the
DNA and damages it.
o The agents cause base pairing errors by increasing
ionization and produces gaps in DNA strand.
o Alkylated purine bases are removed by the
phenomenon called depurination.
o Common alkylating agents are : Methylhydrazine,
Temozolomide, Busulfan, Thio-TEPA, Dimethyl
sulphate , Ethyl ethane sulphate.

17.  INTERCALATING AGENTS:
o Ethidium bromide, proflavine, acridine orange are
few intercalating agents.
o The molecules intercalate between the bases od
DNA & disrupt its structure.
o If incorporated during replication, it can cause
frameshift mutation.
o It may also block transcription.
 METAL IONS:
o Nickel, chromium, cobalt, cadmium are common
metal ions that cause mutations.

19. o The metal ions work by producing ROS(reactive
oxygen species), hindering DNA repair pathway,
cause DNA hypermethylation or may directly
damage DNA.
 OTHER CHEMICAL MUTAGENS:
o ROS, benzene, synthetic rubber and rubber products,
sodium azide, aromatic amines, deaminating agents
etc are other mutagens which create different
mutations.

20. BIOLOGICAL MUTAGENS
 Viruses, bacteria and transposon are biological
mutagens.
 VIRUS:
o Virus insert their DNA into our genome and disrupt
the normal function of DNA or a gene.
o Once it inserts DNA, the DNA is replicated
transcribed and translated viral protein instead of our
own protein. Eg: HIV.

21.  BACTERIA:
o Some bacteria can cause inflammation .
o It provokes DNA damage and DNA breakage.
 TRANSPOSONS:
o They are non coding DNA sequences, jumps from
one place to another in a genome and influence
function of genes.

22. TYPES OF MUTATIONS
 The sequence of a gene can be altered in a number
of ways. The types of mutation includes:
Point Mutation
◦ Transition
◦ Transversion
◦ Missense
◦ Nonsense
◦ Silent
Frameshift Mutations.

23. POINT MUTATIONS
 A point mutation or single base substitution is a
type of mutation that causes the replacement of a
single base nucleotide with another nucleotide of
genetic material.
 There are three types : Missense, nonsense and silent.
 It is a random SNP( single nucleotide polymorphism)
mutation in DNA that occurs at one point.

24. CATEGORIZING POINT
MUTATIONS
 TRANSITION/ TRANSVERSION Categorizaton:
 In 1959 Ernst Freese coined the terms ‘’transitions’’
or ‘’transversions’’ to categorize different types of
point mutations.
 Transition: replacement of a purine base with
another purine or replacement of pyrimidine with
another pyrimidine.
 Transversion: Replacement of purine with a
pyrimidine or vice versa.

25.  FUNCTIONAL CATEGORIZATION:
o MISSENSE MUTATIONS:
This type of mutation is a change in one DNA base
pair that results in the substitution of one amino
acid for another in the protein made by a gene
o NONSENSE MUTATION:
 Code for a stop , which can shorten the protein.
 A nonsense mutation converts an amino acid codon
into termination codon
 Causes the protein to be shortened.

26. o SILENT MUTATION:
Codes for same amino acid.
No effect on functioning of protein
Silent mutations are changes in the sequence of
codon that do no alter the encoded amino acid.

27. DISEASES CAUSED BY POINT
MUTATIONS
 Sickle cell anemia:
o Caused by point mutation in the beta-globin chain of
haemoglobin, causing the hydrophillic amino acid
glutamic acid to be replaced with the hydrophobic
amino acid valine at sixth position.
• Cystic Fibrosis:
o A defect in cystic fibrosis transmembrane
conductance regulator (CFTR) gene causes cystic
fibrosis. This causes thick, sticky mucus, salty sweat.
 Color blindness

29. FRAMESHIFT MUTATIONS
 This type of mutation occurs when the addition or
loss of DNA base changes a gene’s reading frame.
 Reading frame consists of group of three bases that
each code for one amino acid
 A frameshift mutation shifts the grouping of these
bases and changes the code for amino acids
 Resulting protein is usually nonfunctional
 Insertions, deletions and duplications can all be
frameshift mutations.

30.  INSERTION:
Mutations in which extra base pairs are inserted into
a new place in the DNA.
 DELETION:
Mutations in which sections of DNA is lost, deleted.
 DUPLICATION:
o A duplication consists a piece of DNA that is
abnormally copied one or more times .
o May alter the function of resulting protein.

31. DISEASES ASSOCIATED
Hypertrophic Cardiomyopathy:
 Most common cause of sudden death in young
people, athelets.
 Caused by mutations in genes encoding proteins of
the cardiac sarcomere
 Mutations in Troponin C gene (TNNC1).
Tay-Sachs Disease:
 Fatal disease affecting central nervous system.
 Found in infants and children.

32. Tay sachs disease

33. Smith Magenis Syndrome:
 Complex syndrome involving intellectual disabilities,
sleep disturbance , behavioural problems and a
variety of craniofacial, skeletal, visceral anomalies
Cystic Fibrosis.
Crohn’s Disease:
 Affects intestine in humans.
 Fat wraps around the intestine.