‘Mutation’ refers to heritable changes in the base sequence of the DNA. The most common types of change are a substitution, an addition or a deletion of one or more bases.
A physical or chemical agent that causes or increases the frequency of mutation is called a ‘mutagen’. The process of producing a mutation is called ‘mutagenesis’.
If mutation occurs in nature without the addition of a mutagen, then, it is referred to as ‘spontaneous mutation’. If it is caused by a mutagen, then, it is called ‘induced mutation’.
A form of induced mutation called ‘site-specific mutagenesis’ is a genetic engineering technique, which is used to construct mutant DNA molecules containing mutations at pre-selected locations.
Classification of Mutations
In multi-cellular organisms such as plants or animals, mutations may occur in the somatic cells of the organism. Somatic cells are the cells that are involved in the growth, repair and maintenance of the organism. Such mutations are referred to as ‘somatic mutations’. A mutation in these cells may lead to cancer and certain of chromosomal mutations may be involved in aging.
Some mutations happen in the germ cells and these mutations may appear in the gametes and then in the offspring produced by sexual reproduction. These mutations are called ‘germ cell mutations’.
Based on the number of bases changed, mutations can be classified as:
- Point mutation—It involves a single changed base pair.
- Multiple mutation—It involves alterations in two or more base pairs.
Point mutation is further classified as:
1. Base substitution: In substitution mutations, a nucleotide with a different nitrogen base replaces a nucleotide in the DNA. The substitution mutations can have a relatively minor effect on the sequence of amino acids, because only one codon in the mRNA is altered.
Based on the consequence of the change in terms of the amino acid sequence, the affected base substitution mutations are classified as:
- Silent or neutral mutations: Normally, no change will take place in the amino acid sequence of the protein or it functions.
- Missense or nonsense mutations: This leads to the formation of a non-functional or truncated polypeptide.
Some example of substitution mutations are depicted in the following figures.
If a base substitution produces a protein that is active at one temperature (lower) and inactive at other temperature (higher temperature), then it is called ‘temperature-sensitive mutation’.
If a mutation generates a stop codon, stopping protein synthesis, then it is referred to as ‘termination or nonsense mutation’.
Temperature-sensitive mutation and termination or nonsense mutation are considered to be ‘conditional mutations’, as they exhibit mutant phenotype only under certain conditions.
2. Frame shift mutations are caused because of the following two processes.
- Base addition and
- Base deletion.
The addition or removal of one or more base pairs leads to insertion or deletion mutation, respectively. Both the processes shift the reading frame of the codons causing frame shift mutation. In addition, it ultimately leads to misincorporation of all subsequent amino acids. These mutations are caused when the molecules such as acridine orange intercalate between successive bases in the DNA and distort the DNA. This distortion of DNA results in bases being inserted or deleted when the DNA is replicated. Disruptions that arise from the insertion of a transposon within a gene also fall in this category of mutation.
The two possible kinds of point mutations are:
- ‘Transitions’ are purine-to-purine or pyrimidine-to-pyrimidine changes:
A → G, G → A, C → T or T → C. - ‘Transversions’ are purine-to-pyrimidine or pyrimidine-to-purine changes:
A → C, A → T, G → C, G → T, C → A, C → G, T → A or T → G.
Point mutations arise by the pairing of bases with inappropriate partners, by the introduction of base analogues into DNA or by chemical mutagens. Bases may rarely mispair, either because of their tautomeric properties or because of other influences such as purines flipping from anti- to synconformations or H2O molecules serving as bridging H-bond donor/acceptors between two mispaired pyrimidines.
Based on the phenotypic expression, mutations may be classified as:
- Forward mutations: They result in the change in the phenotype of the organism from wild type to mutant type.
- Reverse mutations: They result in the change in the phenotype of the organism from mutant type to wild type. These mutations are also known as ‘reversions’ or ‘back mutations’.
Examples: AAA → GAA → AAA (which is lys → glu → lys)
UCC → UGC → AGC (which is ser → cys → ser)
Suppressor mutation
Mutations that occur at one site that completely or partially reverses the effect of the mutation at a different site are called suppressor mutations. These mutations are of two types:
- Intragenic suppressor mutations: These mutations occur on the same gene as the original mutation but at a different site.
- Intergenic suppressor mutations: These mutations occur in a completely different locus.
Induced mutations
An organism may be exposed to a variety of physical, chemical and biological agents that are capable of damaging its DNA. Each of these agents is capable of causing specific damages to the DNA and the resulting mutations are called induced mutation.