Mutation
A change in the sequence of bases in DNA or RNA is called a mutation. In mutation a change that occurs in our DNA
sequence, either due to mistakes when the DNA is copied or as the result of environmental factors
Over a lifetime our DNA can undergo changes or ‘mutations in the sequence of bases A, C, G and T. This results in
changes in the proteins that are made. This can be a bad or a good thing. Mutations can occur during DNA
replication if errors are made and not corrected in time. Mutations can also occur as the result of exposure to
environmental factors such as smoking, sunlight and radiation. Often cells can recognize any potentially mutation
causing damage and repair it before it becomes a fixed mutation. Mutations contribute to genetic
variation within species. Mutations can also be inherited, particularly if they have a positive effect.
Types of Mutations: There are a variety of types of mutations. Two major categories of mutations are -
Germline mutations occur in gametes. These mutations are especially significant because they can be transmitted to
offspring and every cell in the offspring will have the mutation.
Somatic mutations occur in other cells of the body. These mutations may have little effect on the organism because
they are confined to just one cell and its daughter cells. Somatic mutations cannot be passed on to offspring.
Mutation: Mutation may be defined as the change in the nucleotide sequence of the gene. It gives rise to a new
genetic trait or a changed genotype. A cell or an organism which shows the effect of a mutation is called a mutant.
Types of Mutations: There are three types of DNA Mutations: base substitutions, deletions and insertions.
1. Base Substitutions
Point mutation: Single base substitutions are called point mutations. Occur due two substitution of one nucleotide for
another in the specific nucleotide sequence of a gene. It is also called as microlesion. It is reversible and most
common type of mutation
it is of two types:
(a) Transition: Substitution of one Purine for another Purine or one pyrimidine for another pyrimidine
(b)Transversion: replacement of a purine by a pyrimidine, or vice versa.
This base pair substitution may result in one of three kinds of mutation affecting the translation process. Point
mutations that occur in DNA sequences encoding proteins are either silent, missense or nonsense.
To understand various types of mutation let us consider a normal base pair sequence
(a) Missense mutation: When base substitution results in the generation of a codon that specifies a different amino
acid and hence leads to a different polypeptide sequence. Depending on the type of amino acid substitution the
missense mutation is either conservative or nonconservative. For example, if the structure and properties of the
substituted amino acid are very similar to the original amino acid the mutation is said to be conservative and will most
likely have little effect on the resultant protein’s structure / function. If the substitution leads to an amino acid with
very different structure and properties the mutation is nonconservative and will probably be deleterious (bad) for the
resultant protein’s structure / function (i.e. the sickle cell point mutation). in this altered gene triplet produces a codon
in the mRNA which produces a special amino acid which is not present in normal protein. Such proteins may be
functionally inactive or less active than normal one. Example- sickle cell anemia.
(b) Nonsense mutation: In this altered gene triplet produces a chain termination codon in the mRNA which results in
premature termination of protein formation during translation. In this base substitution results in a stop codon
ultimately truncating translation and most likely leading to a nonfunctional protein.
(c) Silent (Neutral) mutation: The altered gene triplet produces an mRNA codon which specifies same amino acid
because codon resulting from mutation is a synonym for the original codon.
2. Deletions
A deletion, resulting in a frameshift, results when one or more base pairs are lost from the DNA. If one or two bases
are deleted the translational frame is altered resulting in a garbled message and nonfunctional product. A deletion of
three or more bases leave the reading frame intact. A deletion of one or more codons results in a protein missing one
or more amino acids. This may be deleterious or not.
3. Insertions
The insertion of additional base pairs may lead to frameshifts depending on whether or not multiples of three base
pairs are inserted. Combinations of insertions and deletions leading to a variety of outcomes are also possible.
* in some cases, insertion and deletion both can occur simultaneously. Combinations of insertions and deletions
leading to a variety of outcomes are also possible.
Mutants (Causes of Mutations):
Errors in DNA Replication: On very rare occasions DNA polymerase will incorporate a noncomplementary base
into the daughter strand. During the next round of replication, the miss incorporated base would lead to a mutation.
This, however, is very rare as the exonuclease functions as a proofreading mechanism recognizing mismatched base
pairs and excising them.
Errors in DNA Recombination: DNA often rearranges itself by a process called recombination which proceeds via a
variety of mechanisms. Occasionally DNA is lost during replication leading to a mutation.
Chemical Damage to DNA: Many chemical mutagens, some exogenous, some man-made, some environmental, are
capable of damaging DNA. Many chemotherapeutic drugs and intercalating agent drugs function by damaging DNA.
Radiation: high-energy electromagnetic radiation (Gamma rays, X-rays) even UV light can interact with compounds
in the cell generating free radicals which cause chemical damage to DNA.
