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MUTATION!

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Mutation
A heritable change in DNA nucleotide sequence
In biology, a mutation is the permanent alteration of the nucleotide
sequence of the genome of an organism, virus, or extrachromosomal DNA or
other genetic elements.
A mutation is any change in the sequence of the DNA encoding a gene. Most
of these mutations are recognized because the phenotype of the organism
has changed.
Mutations occur in all organisms from viruses to humans.
They can occur spontaneously or be induced by mutagenic agents.
Mutation is usually a random, non-adaptive process.
It changes the sequence of amino acids (structure and function of
proteins) and may result in coding sequences for new amino acids in
proteins or not

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Effect of Mutation

1. Somatic cell (nonreproductive cell):Some type of skin

cancers and leukemia result from somatic mutations
Altered DNA will be limited to that cell and its daughter cells. Cancer

2. Germ cell (reproductive cell like an egg or sperm):and

be passed to offspring

All new DNA will contain the same default and it is Genetic diseases
passed on to the next generation.

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1.Somatic mutations
•Mutations that are in the somatic tissues of the body and not transmitted to
progeny.
•The extent of the phenotypic effect depends upon whether the mutation is
dominant or recessive (dominant mutations generally have a greater effect).
•The extent of the phenotypic effect depends upon whether it occurs early or
late in development (early arising mutations have a greater effect).

2.Germinal mutations
•Mutations that are in the germ tissues of the body and transmitted to progeny
•Dominant mutations are seen in the first generation after the mutation occurs
•If a female gamete containing an X-linked mutation is fertilized, the males will
show the mutant phenotype
•Recessive mutations will only be seen upon the chance of mating with an
individual carrying the recessive allele too; thus, the recessive mutation may
remain hidden for many generations.

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TYPES OF MUTATIONS

 Chromosome Mutations- where segments of chromosomes, whole

chromosomes, or entire sets of chromosomes change.
– Deletion
– Inversion
– Translocation
– Nondisjunction
– Duplication
– Changes in number of chromosomes
 Gene Mutations- where the allele of a gene changes

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Deletion
Due to breakage a piece of a chromosome is lost.
Inversion
The chromosome segment breaks off, the segment flips
around backwards, and segment reattaches
Duplication
Occurs when a gene sequence is repeated.

Translocation
Involves two chromosomes that aren’t homologous. Part of one chromosome is
transferred to another chromosome.

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Nondisjunction
Failure of chromosomes to separate during meiosis. Causes gamete to have
too many or too few chromosomes. Disorders-Down Syndrome (three 21st
chromosomes); Turner Syndrome (single X chromosome); Klinefelter’s
Syndrome (XXY chromosomes).

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Changes in number of chromosomes

Polyploidy

Addition of one or more sets of chromosomes.

They may be further:

 Autopolyploidy: Autopolyploidy involves polyploidy, in which the same

basic set of chromosomes are multiplied.
 Allopolyploidy: The polyploidy results due to the doubling of chromosome
number in an F1 hybrid which is derived from two distinctly different
species. The resultant species is called an allopolyploid.

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Aneuploidy
It involves the loss, or gain, of a part of the chromosome set. It refers to a condition
in which one or a few chromosomes are added or deleted from the normal
chromosome number. Hence, the number of chromosomes in aneuploidy can be
greater or smaller than the number of chromosomes in the wild type.
Various types of aneuploidy:
 Nullisomy (2n-2) is the loss of both chromosomes of the homologous pair. This
conditions may be lethal in most organisms.
 Monosomy (2n-1) is the loss of a single chromosome of the homologous pair.
 Trisomy is the gain of an extra chromosome (2n+1). Klinefelter syndrome
(44+XXY/XYY) and Down syndrome are examples of trisomy.

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Gene mutation
1. Point (substitution) Mutation
The most common
Replacement of one base in the coding strand of DNA with another.

Different amino acid

2. Frameshift Mutation
One or more bases is/are added to or deleted from the normal order of
bases in DNA.

All the triplets shift over by one base. Different sequence of amino acids

3. Silent Mutation

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POINT MUTATION

In hemoglobin, substitution of just one amino acid can result in

the fatal disease sickle cell anemia.

No more amino acids are added. A need protein is not

synthesized. The organism may die.

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FRAMESHIFT MUTATION
1. A deletion mutation occurs when one or more
nucleotides is/are lost from a DNA molecule.

2. An insertion mutation occurs when one or more

nucleotides is/are added to a DNA molecule.

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SILENT MUTATION
A silent mutation has a negligible effect to the organism,
because the resulting amino acid is identical.

The mutation has no effect.

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HOW GENE MUTATIONS ARE

PRODUCED?

Mutations that occur during

DNA replication or
recombination or are due to
an unknown cause are said to
be spontaneous. Most,
however, are induced by
external agents called
mutagens.

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MUTAGENS
Radiation
Ionising radiation- X-rays, γ-rays, α-rays, β-rays and neutrons. These are called
ionising radiation because they break chemical bonds, producing ions or other
particles that are so reactive that they combine with almost any molecule with
which they come into contact. If this happens to be DNA, then one base may
be changed into another and acts indirectly on DNA.

Ultraviolet light on the other hand

specifically damages DNA. Where two
thymine bases occur next to each other
along one of the two DNA strands, they
can become linked to form a thymine
dimer. The dimer can be replicated as a
single base, which results in skin cancer.

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Temperature
The rate of all chemical reactions is influenced by temperature. It is reported
that the rate of mutation is increased due to an increase in temperature. For
example, an increase of 10°C temperature increases the mutation rate two or
threefold. Temperature probably affects both the thermal stability of DNA and
the rate of reaction of other substances with DNA.

Chemical Agents
Many chemical substances have been responsible for increasing the mutability
of genes. Any chemical substance that affects the chemical environment of
chromosomes is likely to influence, at least indirectly, the stability of DNA and its
ability to replicate without error.

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Some of the known chemical mutagens include:

Reactive oxygen species (ROS)-These may be superoxide, hydroxyl
radicals and hydrogen peroxide, and large number of these highly
reactive species which are generated by normal cellular processes.

Deaminating agents- such as nitrous acid which can cause transition

mutations by converting cytosine to uracil. Since this pairs with
adenine, the effect is to change a C–G pair into an A–T pair.

Alkaloid from plants, such as those from Vinca species, may be

converted by metabolic processes into the active mutagen or
carcinogen.

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Nitrosamines are an important group of mutagens found in tobacco,

and may also be formed in smoked meats and fish via the interaction
of amines in food with nitrites added as preservatives. Other alkylating
agents include mustard gas and vinyl chloride.

Benzene is an industrial solvent and precursor in the production of

drugs, plastics, synthetic rubber and dyes.

Acridine dyes, which become lodged in the DNA helix and interfere
with replication, causing an extra base to be inserted, i.e. a frame-shift
mutation.

Polycyclic aromatic hydrocarbon (PAH), when activated to diol-

epoxides can bind to DNA.

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Biological agents
Transposon is a section of DNA that undergoes autonomous fragment
relocation/multiplication. Its insertion into chromosomal DNA disrupts
functional elements of the genes.

Virus– Viral DNA may be inserted into the genome which disrupts genetic
function. Infectious agents have been suggested to cause cancer as early as
1908 by Vilhelm Ellermann and Oluf Bang, and 1911 by Peyton Rous who
discovered the Rous sarcoma virus.

Bacteria– some bacteria such as Helicobacter pylori cause inflammation during

which oxidative species are produced, causing DNA damage and reducing
efficiency of DNA repair systems, thereby increasing mutation.

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SPONTANEOUS CAUSE OF MUTATION

Errors in DNA Replication
On very, very rare occasions DNA polymerase will incorporate a non-
complementary base into the daughter strand. During the next round of
replication, the miss-incorporated base would lead to a mutation. This, however,
is very rare as the exonuclease functions as a proofreading mechanism
recognizing mismatched base pairs and excising them.

Errors in DNA Recombination

DNA often rearranges itself by a process called recombination which proceeds
via a variety of mechanisms. Occasionally DNA is lost during replication leading
to a mutation.

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Significance of Mutations

Variants in genes (which are caused by mutations) are needed to study the
transmission of traits. Mutations can tell the researcher about the function of a
gene product in a biological system. Mutations are the basis for cancer and
other genetic diseases. Gene mutations serve as the source for most alleles in a
population and are therefore the origin of genetic variation within a
population. Mutations drive evolution, mutations are the raw material upon
which natural selection acts.

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