Mutation

 

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,