An overview on mutation, the general mechanisms, classification based on various characteristics, analogy sentence and genetic disorder of various types based on its classification, a brief description of mutagens agents and consequences of mutation in our body and on other living creatures

1. Mutation Overview
Saad Ahmed Sami, Dept. of Pharmacy, CU
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Mutation
Mutation is any sudden and abrupt changes to the genetic or hereditary material of an organism.
These changes occur suddenly and mostly unexpected. The changes are usually random and
disruptive to the normal functioning of the body. A single nucleotide pair or larger gene segment
of a chromosome can be affected by mutation that may result in different phenotype than normal
leading to genetic variation. Genetic variation may result in genetic disorder as well. Animals,
Fungi, Plants as well as viruses exhibit mutations.
So, we may define mutation as the spontaneous changes that affect the DNA or the genes or
sometimes complete chromosome.
Depending upon the type of mutation that has occurred, treatment may be possible. Cancer is a
disease caused by mutations and is treatable through radiation and chemotherapy. Another
disease caused by mutated cells is Sickle Cell Anemia which has treatment methods being used
currently, but still no cure.
 Mutations can be inherited.
This means that if a parent has a mutation in his or her DNA, then the mutation is passed on to
his or her children. Only mutations in gametes are passed onto the offspring. Mutations in the
body cells only affect the organism in which they occur and are not passed onto the offspring.
 Mutations can be acquired.
This happens when environmental agents damage DNA, or when mistakes occur when a cell
copies its DNA prior to cell division.
Some Terminologies
 Individuals showing changes due to mutation are known as mutants.
 Individuals showing an altered phenotype due to mutation are known as variants.
 Factors or gene causing mutations are known as mutagens.

2. Mutation Overview
Saad Ahmed Sami, Dept. of Pharmacy, CU
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Characteristics of Mutation
1. Generally mutant alleles are recessive to their wild type or normal alleles.
2. Most mutations have harmful effect, but some mutations are beneficial.
3. Spontaneous mutations occur at very low rate.
4. Some genes shows high rate of mutation such genes are called as mutable gene.
5. Highly mutable sites within a gene are known as hot spots.
6. Mutation can occur in any tissue/cell (somatic or germinal) of an organism.
Molecular Mechanisms of Mutation
Mutations arise in two ways:
(A) During DNA replication, double strands of DNA are separated. Each strand is then copird to
become another double strand. About 1 out of every 100,000,000 times, a mistake occurs during
copying, which can lead to a mutation.
Some mutations are spontaneous errors in replication that evade the proofreading function of the
DNA polymerases that synthesize new polynucleotides at the replication fork These mutations
are called mismatches because they are positions where the nucleotide that is inserted into the
daughter polynucleotide does not match, by base pairing, the nucleotide at the corresponding
position in the template DNA (Figure A). If the mismatch is not corrected in the daughter double
helix then one of the granddaughter molecules produced during the next round of DNA
replication will carry a permanent, double-stranded version of the mutation.
(B) Other mutations arise because a mutagen has reacted with the parent DNA, causing a
structural change that affects the base-pairing capability of the altered nucleotide. Usually this
alteration affects only one strand of the parent double helix, so only one of the daughter
molecules carries the mutation, but two of the granddaughter molecules produced during the next
round of replication will have it (Figure B).
Mutagenic agents are usually classified as chemical or physical mutagens.

3. Mutation Overview
Saad Ahmed Sami, Dept. of Pharmacy, CU
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I. Physical Mutagens
 Radiation
 Ionizing ( e.g. X-ray, gamma ray, cosmic ray)
 Non-ionizing (e.g. UV ray)
 Heat
 Break the N-glycosidic bond in DNA
 Result from apurinic site or base less site
II. Chemical Mutagens
 Base analogues: Hydroxylamine, 5-Bromouracil, 2-Aminipurine
 Intercalating agents: Aflatoxin, Benzopyrene, Ethidium bromide
 Alkylating agents: Nitrogen, Mustard, Ethylene oxide

4. Mutation Overview
Saad Ahmed Sami, Dept. of Pharmacy, CU
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Consequences of Mutation
Mutations can be-
1) Helpful:
Helpful Mutations improve the organism’s chance for survival, reproduction and diversity
 Examples of Helpful Mutations can be Poison Dart Tree Frog. Poison dart frogs are
normally bright blue, red or yellow in color. Mutations making it green in color resulting
in helpful mutation because it can’t be easily seen among the green trees. Therefore, it
has an increased chance of surviving because predators can’t see it easily.
 Increase biodiversity, turn off harmful genes and produce new version of protein that can
be essential for evolution.
 Hemoglobin in the RBC carries O2. But in case of an individual who inherits one copy of
mutated gene, they don’t have the disease sickle cell anemia, instead they show
protective response against malaria. Even if they get malaria, their symptoms are less
severe.

5. Mutation Overview
Saad Ahmed Sami, Dept. of Pharmacy, CU
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 Scorpion with an extra stinger
2) Harmful:
They reduce the organism’s chance for survival and reproduction.
 Any mutation can lead to diseases such as Cancer- overexposure to UV-light, Cystic
fibrosis , Turners syndrome, Sickle-Cell Disease ,Hemophilia ,Down Syndrome.
 Protein malfunction and stop the fetus development.
 The mutation of bacteria can lead to antibiotic resistance that is also harmful for us.
 In case of an albino tree frog, It has a harmful mutation because it can be easily seen
among the green trees. Therefore, it has a decreased chance of surviving because
predators can see it easily.
3) Neutral (No Effect):
These mutations do not show any advantages or disadvantages to an organism. In fact, many
organisms may have mutated genes and not know it because it does not show through on its
phenotype and does not affect the structure or function of the gene in the cell at all. We consider
a codon CUU codes for leucine. Suppose, it gets mutated and transformed to CUC that still codes
for leucine. It is a silent mutation. Silent mutation is an example of Neutral Mutation.
Classification of Mutation
If we consider a small section of DNA, one base may be deleted or inserted. So, the sequence of
gene will change resulting in change in the reading frame. Any change in the single nucleotide
will change the entire codon. So, it will alter the gene and give rise to defective protein
(harmful). We can divide the mutation based on the genetic material and chromosome.

6. Mutation Overview
Saad Ahmed Sami, Dept. of Pharmacy, CU
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A) Chromosomal Mutation:
It can be divided into two types-
i) Chromosomal aberrations: Based on the alteration of structure of Chromosome.
ii) Aneuploidy: Based on the alteration of number of Chromosome.
Chromosomal aberrations
Once a normal chromosomal structure gets altered, it is called chromosomal aberrations. These
are described below-
 Deletion: Small part removed due to breakage. A piece of chromosome segment is lost.
As a result segment having important gene is also lost. It can lead to severe
abnormalities. Example include- William’s syndrome, Wolf- Hirschhorn syndrome.
 Duplication: Here, Part of chromosome is duplicated resulting in the increase of the
chromosome length. This can lead to severe abnormalities. Example include- Charcot-
Marie-Tooth disease.
 Inversion: Chromosome segment breaks off and the segment flips around backwards and
reattaches. It may or may not be harmful depending on the gene which gets flipped.

7. Mutation Overview
Saad Ahmed Sami, Dept. of Pharmacy, CU
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 Insertion: A part of the Chromosome gets inserted to another chromosome. Both the
chromosome change drastically resulting in severe abnormalities.
 Translocation: Involves two chromosomes that are not homologous. A segment from
each chromosome gets inter exchanged. Abnormalities occur as both the chromosome
altered completely. Example include- XX male syndrome.
Aneuploidy
It means change in the number of chromosome. Abnormal number of chromosome is present in
the cell. It can occur in both sex chromosome and autosome.
Types of Aneuploidy:
a) Nullisomy: loss of a chromosome pair ( 2 chromosomes)
b) Monosomy: loss of a single chromosome
c) Trisomy: Addition of an extra chromosome

8. Mutation Overview
Saad Ahmed Sami, Dept. of Pharmacy, CU
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d) Tetrasomy: Addition of two extra chromosomes
Examples include-
 Down syndrome: It is caused by trisomy 21, that is the addition of an autosome in the
21st
chromosome. It alters the chromosome number (2n=47)
 Klinefelter syndrome: Individuals having an additional X chromosome in their sex
chromosome resulting in Klinefelter syndrome. It is the presence of both masculine and
feminine characteristics. It alters the chromosome number (2n=47)
 Turner syndrome: It is the deletion of an X chromosome in the sex chromosome in
women resulting in Turner syndrome. It alters the chromosome number
(2n=45).

9. Mutation Overview
Saad Ahmed Sami, Dept. of Pharmacy, CU
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It also include Edwards Trisomy 18 (addition of an autosome in the 18th
chromosome), Jacob’s
Syndrome in Men (XYY, 2n=47) and many other diseases as well.
B) Genetic Mutation:
EFFECTS OF GENE MUTATIONS
i. Most mutations are neutral they have no effect on the polypeptide.
ii. Some mutations result in a less active product;
iii. Less often an inactive product;
iv. Very few mutations are beneficial.
v. Affects molecular changes in the DNA sequence of a gene
vi. Alter the coding sequence within a gene
vii. Causes permanent change in DNA sequence
Genetic mutation can be of 3 types,
 Point mutations: A change in the DNA sequence at a single base pair.
 Silent: Silent mutation single base substitution in the 3rd
base nucleotide position
of a codon. This results in no change in amino acid. The first 2 letters of the
genetic code are the most critical.
 Nonsense: Single base substitutions that change a normal codon to a
termination/stop codon. There are 3 nonsense codons in the genetic code. It means
no protein.

10. Mutation Overview
Saad Ahmed Sami, Dept. of Pharmacy, CU
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 Missense: Single base substitution in 1st or 2nd base nucleotide position. This
results in changed amino acid. This is equivalent to changing one letter in a
sentence. Example: Sickle-cell anemia
 Conservative- No change in the nature of the amino acid
 Non- Conservative- Change in the nature of the amino acid
 Base substitution mutation: The replacement of one base pair to another.

11. Mutation Overview
Saad Ahmed Sami, Dept. of Pharmacy, CU
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 Transitions: when a purine is replaced with a purine, or a pyrimidine with a pyrimidine.
 Transversions: when a purine is replaced with a pyrimidine, or vice versa.
 Frameshift mutations: Mutations in which a single base is added or deleted from DNA.
Adding/deleting one base changes every amino acid in the protein after. Our cells read
DNA in three letter "words", adding or removing one letter changes each subsequent
word. This type of mutation can make the DNA meaningless and often results in a
shortened protein & non-functional.
It can occur by two ways-
 Addition or Insertion
 Deletion

12. Mutation Overview
Saad Ahmed Sami, Dept. of Pharmacy, CU
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13. Mutation Overview
Saad Ahmed Sami, Dept. of Pharmacy, CU
Page | 13
Other Basis of classification:
 Based on the survival of an individual
I. Lethal mutation- when mutation causes death of all individuals undergoing mutation
are known as lethal. It is the most extreme example of deleterious mutations.
II. Sub lethal mutation - causes death of 90% individuals.
III. Sub vital mutation- such mutation kills less than 90% individuals.
IV. Vital mutation -when mutation doesn't affect the survival of an individual are known
as vital.
V. Supervital mutation - This kind of mutation enhances the survival of individual. This
is a beneficial mutation.
 Based on causes of mutation
I. Spontaneous mutation- Spontaneous mutation occurs naturally without any cause. The
rate of spontaneous mutation is very slow eg- Methylation followed by deamination of
cytosine. Rate of spontaneous mutation is higher in eukaryotes than prokaryotes.
Example-. UV light of sunlight causing mutation in bacteria.
II. Induced Mutation- Mutations produced due to treatment with either a chemical or
physical agent are called induced mutation. The agents capable of inducing such
mutations are known as mutagen. use of induced mutation for crop improvement program
is known as mutation breeding. Example- X-rays causing mutation in cereals.
 Based on tissue of origin
I. Somatic mutation- A mutation occurring in somatic cell is called somatic mutation. In
asexually reproducing species somatic mutations transmits from one progeny to the next
progeny.
II. Germinal Mutation- When mutation occur in gametic cells or reproductive cells are
known as germinal mutation. In sexually reproductive species only germinal mutation are
transmitted to the next generation.

14. Mutation Overview
Saad Ahmed Sami, Dept. of Pharmacy, CU
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 Based on direction of mutation
I. Forward mutation- When mutation occurs from the normal/wild type allele to mutant
allele are known as forward mutation.
II. Reverse mutation- When mutation occurs in reverse direction that is from mutant allele to
the normal/wild type allele are known as reverse mutation.
 Based on the type of trait affected
I. Visible mutation- Those mutation which affects on phenotypic character and can be
detected by normal observation are known as visible mutation.
II. Biochemical mutation- mutation which affect the production of biochemicals and which
does not not show any phenotypic character are known as biochemical mutation.
 Based on the second site of mutation
These second-site mutations are called suppressor mutations or simply suppressors.
I. Intragenic suppressors- The second mutant site is within the same gene as the first
mutation
II. Intergenic suppressors- The second mutant site is in a different gene from the first
mutation