Mutation: Characteristics, Types and Applications

The transfer and distribution of genetic material is an extremely precise process, making sure that genetic information is not altered while passing on from one generation to the next. Even with high levels of precision, some occasional errors do occur during replication and distribution of the genetic material, giving rise to sudden heritable character in organisms. Such alteration is called mutation. Those individuals that express these heritable alterations phenotypically are known as mutants. Thus, simply stated, mutation is a sudden heritable change in the phenotype of an organism that is not produced due to segregation or recombination.¹ Mutation is essential for variation and biological diversity.

1.1. History:

English farmer Sen Wright discovered a male lamb with unusually short legs. It was the earliest record made regarding sudden heritable changes (mutation) till date. The term mutation was introduced by Hugo de Fries in 1900, during his study on Oenothera.¹The earliest systematic studies on mutation were performed by T.H. Morgan in 1910. He discovered and genetically analysed the white eye mutant of Drosophila melanogaster (deviation from normal red eye).²

1.2. Occurrence of Mutation:

Mutation occurs frequently in nature in a random manner. It has been reported in various organisms, including Drosophila, mice, rabbits, rats, guinea pigs, and humans. In Drosophila, mutations are observed in terms of colour of eyes (white, pink), body colour (black, yellow) and vestigial wings. However, in Rodents, mutations are expressed in body coats (black, brown, white). In humans, mutation is responsible for variation in eye colour, hair colour, skin pigmentation, and various somatic malformations. Many genetic diseases, including Haemophilia, Colourblindness, Phenylketonuria, etc result from mutation.³

1.3. Characteristics of mutation:

The mutant alleles are generally recessive to their wild-type or normal alleles. However, some mutations are dormant. Example: Epiloia in humans, Notch wing in Drosophila, etc.
Some sites within genes show higher rates of mutation than others. These highly mutable sites are known as hot spots.
The frequency of mutation is increased by various physical and chemical agents known as mutagens.
Mutation can occur in the tissue / cell of an organism during any developmental stage of the organism.
Spontaneous mutation occurs at very low frequencies (10^-4-10^-7) in nature without any definite cause.
Some genes, called mutable genes, show an exceptionally high tendency for spontaneous mutation.
Some genes, called mutator genes, increase the rate of spontaneous mutation of other genes of the genome. Likewise, antimutator genes reduce the rate of mutation of some other gene of the genome.
Mutation can occur in both forward (from wild-type allele to mutant allele) and reverse (from mutant allele to wild-type allele) directions. Generally, the rate of forward mutation is higher than that for reverse mutation.¹

1.4. Cause of mutation:

On the basis of the cause of their origin, mutations are classified as spontaneous mutation and induced mutation.

Spontaneous mutation tends to occur naturally without any known cause. The rate of spontaneous mutation is very low. The rate of spontaneous mutation is determined to be higher in eukaryotes than prokaryotes.¹ Possible sources of origin of spontaneous mutation are normal cellular events and mutagenic effects of the environment. The normal cellular events include: i) errors during DNA replication ii) methylation followed by deamination of cytosine and iii) activities of transposable elements i.e. DNA sequences which can change their location in the genomes. Spontaneous mutations caused by environmental factor is not clearly understood. Some solar radiations (e.g., UV rays) are proven to be mutagenic and are likely to contribute towards spontaneous mutations.

Induced Mutation: Mutation which occurs as a result of treatment with chemical or physical agent is known as induced mutation. Mutagens are responsible for such mutations. The process of inducing mutation through treatment with a mutagen or mutagenic agent is called mutagenesis. The mutagen or mutagenic agent can be of the following types:

I) Radiation: the radiations involved in mutagenesis are further divided into two categories: ionizing radiation and non-ionizing radiation

Ionizing radiation: It includes X-rays and gamma rays. When ionizing radiation is passed through matter, a negatively charged electron is ejected from the atom. The ejected electron moves at high speed and knocks off other electrons from their atoms until its energy is dissipated. Since the atom has a tendency to gain the most stable configuration, these ions undergo many chemical reactions, resulting in mutation. Ionizing radiations cause breakage in the polysugar-phosphate backbone of DNA, causing chromosomal mutations.
Non-ionizing radiation: It includes UV light. UV light of about 2,600 A wavelength is most effective for inducing this type of mutation. When a substance absorbs UV light, some of the electrons are raised to higher energy levels. These excited molecules become reactive and mutate.

II) Temperature: It has been established that the rate of mutation increases with an increase in temperature. Temperature affects the thermal stability of DNA and the rate of reaction of other substances with DNA.

III) Chemical mutagens: A chemical substance can cause mutation only when it enters the nucleus of the cell. Some chemicals affect DNA directly, causing genetic changes, and others cause replication errors. Nitrous acid, formaldehyde, ethyl methane sulphonate (EMS), carcinogens, caffeine, and manganese chloride are some of such mutagenic agents.²

On the basis of alteration in nucleotide sequence of the genome, mutation can be of following types:

A. Non-sense mutation: When a nucleotide is changed, the triplet formed may not code any amino acid. Such code may lead to the termination of a polypeptide in the middle, and the protein produced may be functionless. This type of mutation is known as non-sense mutation or chain termination mutation.

B. Mis-sense mutation: It involves substitution or deletion of one, two, or all of the nucleotides in a triplet. This gives rise to altered amino acid which eventually may alter the biological function of the protein.

C. Silent mutation: In many cases, mutation causing a change in the base sequence of DNA does not get reflected in mRNA. A change in the third base (Wobble hypothesis) makes no difference in translation. ²It is also supported by the fact that there are more than one triplet codes for each amino acid. These types of mutations normally go unnoticed.

D. Frameshift mutation: addition or deletion of a single base in the nucleotide sequence of DNA may cause change in the reading frame. This change alters the entire triplet codon and affects the translation of the polypeptide chain.³

Fig: Types of mutation on the basis of various alterations in nucleotide sequence. (Source: Microbiology 2e, Openstax)

1.5. Application of Mutation:

Some mutations have been extensively observed and studied for crop improvement. Mutations in various qualitative and quantitative traits have been exploited for the development of more than 2000 crop varieties.
Mutation in a gene allows for the gene to be identified. For example, the white eye locus was identified after the white-eyed mutant of Drosophila was discovered.¹
Mutation makes structure analysis of genes easier. It also helps to decode the relationship between a particular gene and protein.
Induced mutations are widely used for analyzing the effects of various types of alterations in DNA on the expression of the concerned trait.²

REFERENCE

B.D. Singh. Genetics. Second. Kalyani Publishers; 2018.
Dr. P.S. Verma, Dr. C.K. Agrawal. Cell Biology, Genetics, Molecular Biology, Evolution and Ecology. fourteenth. (Bharatnagar S, Pradhan S, eds.). S.CHAND & COMPANY PVT.LTD.; 2016.
S.C. Rastogi. Cell and Molecular Biology. Third edition. New Age International Publishers