Introduction:
Introduction:
- Mutation is the permanent alteration of the nucleotide sequence of the genome of an organism.
- A mutation is a change or alteration in a DNA, gene, or chromosome that occurs as a result of intrinsic or extrinsic factors such as replication error or UV light exposure, respectively.
- Mutations can occur due to errors during DNA replication (replication-dependent mutations)
- Mutations can also occur independently of DNA replication (replication-independent mutations)
- May occur in somatic or germ-line cells:
- Somatic mutations are not inherited and thus play no major role in evolution.
- In cases of antibody formation and malignant transformation, somatic mutations are significant.
- Only germ-line mutations are inherited and thus are important in evolution.
Mutagens:
Mutagens are chemical or physical agents that interact with DNA to cause mutations.
Physical agents include high-energy radiation like X-rays and ultraviolet light.
Fig: Commonly used physical mutagens and their properties and mode of action
Chemical mutagens fall into several categories.
- Chemicals that are base analogues that may be substituted into DNA, but they pair incorrectly during DNA replication.
- Interference with DNA replication by inserting into DNA and distorting the double helix.
- Chemical changes in bases that change their pairing properties.
Fig: Commonly used chemical mutagens and their mode of action
In multicellular organism, two broad categories of mutations: Somatic mutations & germ line mutations
- Somatic mutations occur in somatic cells and only affect the individual in which the mutation arises.
- Germ-line mutations alter gametes and passed to the next generation.
Mutations are quantified in two ways:
Mutation rate = probability of a particular type of mutation per unit time (or generation).
Mutation frequency = number of times a particular mutation occurs in a population of cells or individuals.
Effects of Mutations:
Mutations categorized by effect on fitness
Beneficial mutation
Beneficial mutations may produce proteins with new or altered activities that can be useful to organisms in different or changing environments. Plant and animal breeders often take advantage of such beneficial mutations. The condition in which an organism has extra sets of chromosomes is called polyploidy. Often larger and stronger than diploid plants, but not beneficial in animals
Harmful mutation
This mutation that decreases an organism’s fitness
Neutral mutation
This mutation that does not affect an organism’s fitness. There is no change in any proteins. All silent mutations are neutral mutations
Classification of Mutations:
Based on direction of mutation
- Forward mutation: Any change from wild type allele to mutant allele.
- Backward mutation or reverse mutation: A change from mutant allele to wild type.
Based on source/case of mutations
- Spontaneous mutation: Mutation that occur naturally.
- Induced mutation: Mutation that originates in response to mutagenic treatment
Based on tissue of origin
- Somatic mutation: A mutation in somatic tissue.
- Germinal mutation: A mutation in germline cells or in reproductive tissues.
Based on effect on survival
- Lethal mutation: Mutation which kills the individuals that carried it. (Survival 0%)
- Sub-lethal mutation: When mortality is more than 50% of individual that carry mutation
- Sub-vital mutation: When mortality is less than 50% of individual that carry mutation
- Vital mutation: When all the mutant individuals survive (Survival -100%)
Based on trait or character effected
- Morphological mutation: A mutation that alters the morphological features of an individual
- Biochemical mutation: A mutation that alters the biochemical function of an individual
Based on visibility or quantum of morphological effect produced
- Macro-mutations: Produce a distinct morphological change in phenotype (which can be detected easily without any confusion due to environmental effects) E.g., Colour of flowers, height of plant etc.
- Micro-mutations: Mutation with invisible phenotypic changes, (which can be easily confused with effects produced due to environment).
Based on the site of mutation or on cytological basis
- Chromosomal mutations: Mutations associated with the detectable change in either chromosome number or structure.
- Gene or point mutations: Mutations produced by alternation in base sequences of concerned genes.
- Cytoplasmic mutations: Mutations associated with the changes in chloroplasts DNA (cpDNA) and mitochondrial DNA (mt DNA).
Gene Mutation:
Types of Gene Mutations
There are a number of ways to classify gene mutations. Some classification schemes are based on the nature of the phenotypic effect (mutation alters the amino acid sequence of the protein). Other schemes are based on the causative agent of the mutation, and still others focus on the molecular nature of the defect.
The most appropriate scheme depends on the reason for studying the mutation. Here, we will
categorize mutations primarily on the basis of their molecular nature, but we will also encounter some terms that relate the causes and the phenotypic effects of mutations.
Base substitutions
The simplest type of gene mutation is a base substitution, the alternation of a single nucleotide in the DNA. Base substitutions are of two types. In a transition, a purine is replaced by a different purine or, alternatively, a pyrimidine is replaced by a different pyrimidine. In a transversion, a purine is replaced by a pyrimidine or a pyrimidine is replaced by a purine.
Fig: Point mutations
Insertions and deletions
The second major class of gene mutations contains insertions and deletions—the addition or the removal, respectively, of one or more nucleotide pairs. Insertions and deletions within sequences that encode proteins may lead to frame shift mutations, changes in the reading frame of the gene.
Duplication
A duplication consists of a piece of DNA that is abnormally copied one or more times. This type of mutation may alter the function of the resulting protein.
Missense mutation
This is a base substitution that alters a codon in the mRNA, resulting in a different amino acid in the protein.
Nonsense mutation
It changes a sense codon (one that specifies an amino acid) into a nonsense codon (one that terminates translation). If a nonsense mutation occurs early in the mRNA sequence, the protein will be greatly shortened and will usually be non-functional.
Frameshift Mutation
This type of mutation occurs when the addition or loss of DNA bases changes a gene’s reading frame. A reading frame consists of groups of 3 basest hat each code for one amino acid. A frameshift mutation shifts the grouping of these bases and changes the code for amino acids. The resulting protein is usually non-functional. Insertions, deletions, and duplications can all be frameshift mutations.
Fig: Frameshift Mutation
Chromosomal Mutation:
Any alteration or error within the chromosome is known as a chromosomal mutation. Any errors or consequences that occur during cell processes such as mitosis and meiosis might be responsible for such errors.
Unlike gene mutations, which occur when a gene or a piece of DNA in the chromosome is changed, chromosomal mutations occur once the entire chromosome is changed.
There are three types of chromosomal mutations: chromosome structural mutations and chromosome number mutations.
Structural Chromosomal Mutations
This type of chromosomal mutation is most common when cells divide incorrectly. When homologous chromosomes couple up, genes in chromosomes break apart, genes are inserted in the wrong chromosome, or a gene or set of genes is completely lost in the chromosome.
Basically, structural chromosomal mutations are classified into four: deletion, duplication, inversion, and translocation.
Fig: Structural Chromosomal Mutations
Chromosomal Number Mutations
Aneuploidy is a chromosome number mutation in which the new individual’s chromosome number differs from the wild type. This is usually caused by chromosome nondisjunction during mitosis or meiosis, resulting in offspring with extra or missing chromosomes. The naming of aneuploid conditions is generally based on the number of chromosomes added or deleted. For instance, a monosomic (2n -1) individual bears only one copy of a chromosome, instead of having two.
Other variations of aneuploidy are trisomic (2n+1), nullisomic (2n-2), and disomic (n+1).
Polyploidy is a subtype of mutation in which a person has more than one haploid set of chromosomes. Triploid occurs when an individual with polyploidy has three sets of haploid chromosomes, whereas tetraploid occurs when the individual has four sets of haploid chromosomes. Polyploidy is a widespread occurrence in plants, fish, salamanders, frogs, and leeches, among other animals.
Fig: Chromosomal Number Mutations
References:
- Euploidy: Meaning and Types | Cell Biology. Biology Discussion, 14 July 2016.
- Loewe, L. (2008) Genetic mutation. Nature Education 1(1):113
- Orr, H. A. The genetic theory of adaptation: A brief history. Nature Review Genetics 6, 119–127 (2005)
- Montelone BA (1998). “Mutation, Mutagens, and DNA Repair”. www-personal.ksu.edu. Archived from the original on 26 September 2015. Retrieved 2 October 2015.