Definition of Mutation
A
mutation is a change in the nucleotide sequence of an organism's DNA. These
changes can affect a single gene or entire chromosomes. Mutations can occur
spontaneously due to errors during DNA replication or be induced by
environmental factors known as mutagens. DNA, or deoxyribonucleic acid, is the
molecule that carries the genetic instructions used in the growth, development,
functioning, and reproduction of all known living organisms. Mutations can
occur in somatic cells (body cells) or germ cells (sperm and egg cells). If a
mutation occurs in a germ cell, it can be passed on to offspring, making it a
hereditary mutation. Mutations in somatic cells, on the other hand, cannot be
inherited but may lead to cancer or other diseases within the individual.
Mutations
are a natural part of the evolutionary process, providing the raw material for
natural selection. While many mutations are neutral or harmful, some can
provide advantages that help organisms adapt to their environments.
Types of Mutation:
Mutations can be classified based on different criteria:
A. Based on the Type of
Genetic Material Affected
1. Gene Mutations:
These
involve changes in the nucleotide sequence of a specific gene. Gene mutations
can affect a single nucleotide or larger segments of a gene and can alter the
function of the protein that the gene encodes.
Example: A point mutation in the HBB gene leads
to sickle cell anaemia.
2. Chromosomal
Mutations:
These
involve changes in the structure or number of entire chromosomes. Such
mutations can lead to large-scale changes in the genetic material and have more
profound effects.
Example:
Down syndrome, caused by an extra copy of chromosome 21 (trisomy 21).
B. Based on the Nature
of the Change in the DNA Sequence
1. Point Mutations:
A
change affecting a single nucleotide base pair in the DNA sequence. This can
occur due to errors in DNA replication or be induced by mutagens.
Types of Point Mutations:
a. Substitutions:
A single base is substituted by another.
b. Silent
Mutations: The substituted base results in a codon that still codes for the
same amino acid, leaving the protein unchanged.
Example: The codons GAA and GAG both
code for the amino acid glutamate, so a substitution here would be silent.
c. Missense
Mutations: The substitution changes a codon so that it codes for a
different amino acid, potentially altering the protein's function.
Example: The mutation causing sickle
cell disease changes the codon GAG (glutamate) to GTG (valine).
d. Nonsense
Mutations: The substitution creates a stop codon, prematurely terminating
the protein, which usually results in a nonfunctional protein.
Example: Duchenne muscular dystrophy
can result from a nonsense mutation in the DMD gene.
2. Insertions and
Deletions:
Insertions:
Addition of one or more nucleotide pairs into the DNA sequence.
Deletions:
Loss of one or more nucleotide pairs from the DNA sequence.
Frameshift
Mutations: When insertions or deletions are not in multiples of three, they
shift the reading frame of the gene, drastically altering the amino acid
sequence downstream.
Example: The BRCA1 gene can have deletions
that cause frameshift mutations, increasing the risk of breast cancer.
C. Based on the Effect
on Protein Function
1. Loss-of-Function
Mutations:
These
mutations result in a reduced or completely lost function of the protein. This
can occur if the mutation leads to the production of a truncated or improperly
folded protein.
Example: Cystic fibrosis is caused by
loss-of-function mutations in the CFTR gene, leading to defective chloride
channels in cells.
2. Gain-of-Function
Mutations:
These
mutations lead to a protein that has a new or enhanced function, which may or
may not be beneficial to the organism.
Example: A gain-of-function mutation in the
FGFR3 gene leads to achondroplasia, a form of dwarfism.
D. Based on the
Phenotypic Effect
1. Lethal Mutations:
Mutations that lead to the death of the
organism, either during embryonic development or after birth.
Example: Certain mutations in the HEXA gene
cause Tay-Sachs disease, which is fatal in early childhood.
2. Conditional
Mutations:
These mutations only express their effects
under certain environmental conditions.
Example: Temperature-sensitive mutations in
fruit flies affect wing development only at certain temperatures.
3. Beneficial
Mutations:
Mutations that provide an advantage to the
organism in its environment, increasing its chances of survival and
reproduction.
Example:
A mutation in the CCR5 gene confers resistance to HIV infection.
4. Neutral Mutations:
These
mutations do not affect the fitness of the organisms and often occur in
non-coding regions of DNA.
Example:
A mutation in a non-coding region of DNA that does not affect gene expression
or function.
You can also read Lethal Alleles, Penetrance and Expressivity, Comparison of Nuclear and Extranuclear Inheritance,
