Mutation is any heritable change in DNA base sequence. Copying errors, breaks and damage to nucleotide if not corrected can lead to mutations. Substitution, addition, deletion are the most common types of mutations.
A mutagen is a chemical or physical agent that can bring about a permanent alteration or change to the composition of a DNA such that the genetic message of the gene is changed. The process of creating a mutation is called as mutagenesis. It can be spontaneous (without the addition of any mutagen), induced (caused by a mutagen) or site-specific (genetic engineering techniques are used to construct mutant DNA molecule).
Causes of mutations:
Spontaneous lesions: Spontaneous lesions can cause mutations. Two of the most frequent spontaneous lesions result from depurination and deamination.
Depurination: It is the more common of the two. It is the variation of the glycosidic bond between the base and deoxyribose and the subsequent loss of a guanine or an adenine residue from the DNA. If these lesions persist, they would result in significant genetic damage; because in replication the resulting apurinic sites cannot specify a base complementary to the original purine.
Deamination: The deamination of cytosine yields uracil.
Oxidatively damaged bases: It represents a third type of spontaneous lesion implicated in mutagenesis. Active oxygen species, such as superoxide radicals (O2), hydrogen peroxide (H2O2) and hydroxyl radicals (OH), are produced as by-products of normal aerobic metabolism. They can cause oxidative damage to DNA, as well as to precursors of DNA (such as GTP), which results in mutation and which has been implicated in a number of human diseases.
Errors in DNA replication: An error in DNA replication can occur when there is base substitution, addition or deletion during synthesis. Each of the four bases in DNA has several forms, called tautomers, which are isomers that differ in the positions of their atoms and in the bonds between the atoms. The forms are in equilibrium.
The ability of the wrong tautomer of one of the standard bases to mispair and cause a mutation in the course of DNA replication.
i. Mispairs resulting from rare tautomeric forms of the pyrimidines.
ii. Mispairs resulting from rare tautomeric forms of the purines.
Types of mutations
Mutations can be classified in many ways like:
Somatic or germ line mutations: Somatic mutations are mutations that occur in a somatic cell, in the bone marrow or liver. They may damage the cell, make the cell cancerous or even kill the cell. It is never passed to the next generation. Germ line mutations are those in which the mutated DNA can be passed to the next generations. It is present in a germ cell such as spermatozoa and ova.
Inherited or acquired mutations: The mutations can be inherited which means the mutated genetic code can be passed on to the next generations. For example heart disease, diabetes, stroke or high blood pressure. Mutations can be acquired type, depending on what type of environment or surroundings a person lives in, as some environmental agents can damage the DNA or when mistakes occur during cell division. For example radiations released during the nuclear disasters in Hiroshima and Nagasaki has caused mutations in the genetic makeup of the people living in those areas. Different types of cancers are also caused by mutations.
Point mutations: These are the mutations, which involve a single change in base pair.
They may be base addition, substitution or deletion:
i. Base substitution: A substitution is a mutation in which there is an exchange between two bases. Substitution mutations can change a codon to one that encodes a different amino acid and cause a change in the protein produced. Sometimes substitutions may not affect the protein structure such mutations are called silent mutations and sometimes they may change an amino acid coding codon to a single “stop” codon AUG and cause an incomplete protein, which will affect the protein configuration, which may completely change the organism.
ii. Base addition (insertion): The mutations in which extra base pairs are inserted into a new place in the DNA.
iii. Base deletions: The mutations in which a base pair or many base pairs of DNA is either lost or deleted.
Frame shift mutations: Protein coding DNA is divided into codons, which are three bases long insertions and deletions. In these codons can completely change a gene and protein encoded by the gene. Such mutations are called frame shift mutations. When the base is frame shifted it codes for a different amino acid. Incorporation of a stop codon gives rise to truncated proteins.
Silent mutations: The mutations in which the altered codon codes for the same amino acid. CGC and CGA both code for arginine. GAG and GAA both code for glutamine.
Missense mutations: In these mutations the altered codon codes for a different and dissimilar amino acid. The protein produced is often nonfunctional.
Nonsense mutations: The codon after mutation is a termination codon that stops the protein synthesis and the protein produced is non-functional.
GAG UAG Glu Stop
Neutral mutations: The altered codon as a result of mutation codes for a different but functionally similar amino acid. The protein produced may be functional.
GAG GAU Glu Asp
Transition and Transversion mutations: Transition mutations are those mutations in which a purine is replaced by a purine and a pyrimidine is replaced by a pyrimidine.
A-T → G-C Transversion mutations are those mutations in which a purine is replaced by a pyrimidine or vice versa A-T → T-A