- A gene mutation is an alteration or change in sequence of DNA or chromosomes which can be described by its genotype.
- Mutation can be more or less permanent and are highly influenced by intrinsic and extrinsic factors.
- Intrinsic factors include the nature of the gene and error in replication while extrinsic factor includes exposure to mutagenic agents that may cause alteration in genes.
- Mutation is a biological process of changing genes that can be helpful in creating new alleles for evolution of cell where sickle cell anemia is one of the best studied example of this phenomenon that provides resistance to malarial disease while on the other side it can be harmful with undesirable mutation causing genetic diseases and disorders like cancer, albinism, down syndrome, cystic fibrosis.
Genetic mutation are divided into two categories:
- Point mutation:
Mutation occurs at a single nucleotide base and is also known as single nucleotide polymorphism.
Insertion or addition of one or more nucleotide base pair which is often caused by DNA polymerase slipping or wrinkling.
In deletion mutation, a sequence or any number of nucleotide base pair is left out or removed which occurs during the synthesis of enzyme .
Inverting and inserting back to the original place causes gene inversion.
When one base of nucleotide gets replaced by other bases then substitution mutation occur that changes a codon and starts encoding different animo acids.
Gene dublication is where evolution occurs when one or more copies of same genes are produced.
- Forward mutation
Forward mutation is the evolution of new mutation from wild type allele. It is responsible for determining phenotype and evolution.
- Backward mutation
Backward or reverse mutation is the restoration of wild phenotype i.e, it is a unidirectional process of forward mutation. It is very rare and unusual but sometime it supresses the effect of forward mutation.
- Copying error
Copying mistake of genes during replication are the main cause of cancer which is mainly influenced by lifestyle and environmental factors.
- Silent mutation
Silent mutation or neutral mutation is non expressive. When a new codon is replaced as the same amino acid having similar properties, little or no change will occur.
- Missense mutation
When a codon codes for different amino acids which results in alteration and protein dysfunction.
- Nonsense mutation
When a stop codons are added in the sequence, it hinder the protein synthesis that results in premature stop codon.
- Frameshift mutation
When a nucleotide is inserted or deleted in which the base pairs are not divisible by three which disrupts the reading frame and cause mutation.
Addition of one or more larger sequence into a chromosome.
A single base or an entire sequence of chromosomes are deleted.
When a section of a chromosome have same repeated copies while other won’t have.
When two segment of chromosomes gets exchanged then it is balanced translocation wheras addition and deletion of each segment forms an unbalanced translocation.
When a segment of chromosomes are inverted and inserted back in only one arm then it is paracentric inversion but if with two arms then it is pericentric inversion.
Additional or missing number of chromosome results in aneuploidy.
Types of mutation causing agents are:
- Physical mutagens
- Chemical mutagens
- Biological mutagens
- Physical mutagens include electromagnetic radiation such as UV rays, X-rays, alpha rays, neutrons and other ionizing as well as non-ionizing radiations.
- These radiations are harmful and directly damages the structure of DNA which might kill the organism or alter its gene.
- The severity of damage depends on the dose and time of exposure on the radiation.
- Heat is also responsible for the denaturation of DNA and is another cause of mutation. Extreme heat (>95°C) breaks the phosphodiester bond of DNA.
- Bromouracil and aminopurine are two common base analogs that are similar to the bases of DNA purine and pyrimidine which are altered during the time of replication and cause mutation.
- Alkylating agents attaches to the DNA and damages it by inducing base pairing errors.
- Alkylating agents like ethylnitrosourea, mustard gas and vinyl chloride can be removed by depurination method.
- Interchalating agents like EtBr – Ethidium Bromide which is commonly used in electrophoresis process induces mutation.
- Other interchalating agents are proflavin, acridine orange and daunorubicin.
- Metal ions like nickel, cobalt, arsenic and iron produces reactive oxygen species that damages and blocks the DNA repair pathway and cause mutation.
- Viruses are the common mutagens that transfers their genetic material and disrupts our DNA function and synthesize viral protein instead.
- Bacteria are also responsible in breaking and blocking DNA replication processes.
- Transposon is a section of non-coding DNA sequences that disrupts the DNA function by altering gene segments.
The Ames test for detection of mutation is one of the common method that can be performed in any laboratory. In this test, bacteria is utilized to test whether the test chemical has potential of causing mutation in DNA or not.
Ames test is carried out by following given procedure:
- Salmonella Typhimurium is common used strain of bacteria that may carry a mutation which is isolate for histidine.
- The chemical to be tested as mutagenic agent is placed with the isolate of bacteria with a plain buffer.
- Another negative control suspension of Salmonella Typhimurium is taken.
- Incubation is done at 37°C for 20 minutes.
- Then, spread the suspension in two agar plates.
- Again incubate at 37°C for 2 days.
- After incubation, observe for the colonies formed. If a large number of colonies are formed then the chemical is said to be mutagenic.