Alterations in one gene or more than one gene cause heritable changes. These changes are known as mutations. A mutant gene affects a phenotype or a trait. The smallest part of a gene getting mutated is known as a muton. The sequence of base pairs in a DNA molecule gets altered. Anything may induce mutations. Radiations, chemicals or any other agents induce mutations. An organism or a cell having the mutant gene(s) is known as a mutant. A mutable site is a site where the mutation occurs. Mutations not only occur at the base pair level or molecular level but also occur at the chromosomal level. Base pair mutations or alterations are known as point mutations. Changes in the heritable traits either occur due to random mutations or due to experimental induction. Errors during DNA replication also induce mutations.

A gene mutation changes the function of a protein by causing a phenotypic change. Two main types of mutations include somatic and germline mutations. A mutation occurring in a somatic cell does not pass on to the succeeding generation. This type of mutation occurring in a somatic cell is known as somatic mutation. Mutations in the germ cells get transmitted to the next generation through gametes. Such type of mutations is known as germ-line mutations. The number of events leading to mutation per gene per unit time is known as mutation rate. It also indicates the proportion of mutations per cell division in an organism. Detecting a mutation is possible with the mutation analysis. It detects a specific type of mutation or a set of mutations. The frequency of mutations in a population is known as mutation frequency.





Types of point mutations:





Image: Mutations

Point mutations alter one or few base pairs and consist of two general categories such as base pair substitutions and base pair deletions or insertions. Based on single base pair substitutions, the point mutations have two main categories. They include transition and transversion mutations. Transition mutation leads to one purine-pyrimidine base pair substitution with another purine-pyrimidine base pair. Transversion mutation is opposite to that of transition mutation. The transversion mutation involves the substitution of one purine-pyrimidine base pair with another pyrimidine-purine base pair. A base pair change translates into a protein. The type of substitution also affects the protein synthesized. Based on the above point let us discuss other types of mutations such as missense mutations, nonsense mutations, neutral mutations, silent mutations, reverse, and suppressor mutations. Spontaneous and induced mutations occur due to mutagenesis. The naturally occurring mutations are known as spontaneous mutations. Induced mutations arise due to experimental induction. Depurination and deamination are the common forms of spontaneous mutations. Depurination involves removal of the adenine or guanine due to DNA bond breakage between the base and the deoxyribose sugar. It results in an apurinic site. Deamination results in the removal of an amino group from a base.

A point mutation involving a base pair change in the DNA also changes the mRNA codon leading to an insertion of different amino acid in the polypeptide. This kind of mutation is known as a missense mutation. A base pair change in the DNA, in some cases, also leads to changes in the mRNA codon to a stop codon. This type of mutation is known as a nonsense mutation. A nonsense mutation may lead to premature termination of the polypeptide chain resulting in the production of shorter polypeptide fragments. A neutral mutation causes a base pair mutation causing no functional change in the protein product. A silent mutation results in same base pair substitution. Both neutral and silent mutations belong to the category of missense mutations. Mutations changing the reading frame due to base pair addition or deletion are known as frameshift mutations. These mutations obstruct the functionality of a protein. They generate new stop codons, alter the normal stop codons, and interfere with the codon messaging. The frameshift mutations either lead to longer than normal proteins or shorter than usual proteins.

The point mutations impose a great effect on the phenotype. Hence, there are two types of point mutations. The genotype changes to a mutant one in case of the forward mutations. Reverse mutations change a mutant genotype to the wild-type one. A suppressor mutation diminishes the effect of a mutation. A suppressor mutation is of two types such as intergenic or intragenic mutation. Intragenic suppressor mutations occur in the gene where original mutations occurred but at a different site. Intergenic suppressor mutations occur in a different gene.





DNA replication errors:

DNA replication involves the semi-discontinuous synthesis of DNA molecules. It is an important cellular process. However, while replicating the DNA, certain errors result in mutations. Sometimes, errors in DNA replication result in a mismatch of base pairs.





Induced mutations:

Mutations get induced due to the exposure of physical, chemical or biological mutagens. A mutagen is capable of inducing a mutation. It is an external agent. Both X-rays and ultraviolet rays are capable of inducing mutations. High doses of radiations typically induce point mutations. Chemical mutagens induce mutations in the DNA. Base modifying agents, base analogs, and intercalating agents are the three types of chemical mutagens. Base analogs resemble the bases found in the DNA. 5-Bromouracil is a common base analog. It has a bromine residue instead of the methyl group of thymine. Base modifying gents modify the chemical structure and properties of the bases. Intercalating agents insert themselves between the adjacent bases in one or both the strands of the DNA double helix. Examples include ethidium bromide, proflavin, and acridine.





References:

[1] Genetics, Hugh L. Fletcher, G. Ivor Hickey

[2] Essentials Of Human Genetics, Bhatnagar, S.M.

[3] Advanced Genetics, By Gurbachan S. Miglani