A mutation is a change in the nucleotide sequence of DNA, either by one or several bases. Mutation has a range of consequences, in terms of both the gene product (usually protein) and the phenotype of the organism, ranging from no consequence at all to potentially fatal consequences.

A physical, chemical or biological causative agent of mutation is called a mutagenic agent (or mutagen for short) and the process of generating a mutation is called mutagenesis. Mutations in the genes and proteins that regulate the cell cycle often result in cancer. Mutagens which specifically trigger a cancerous phenotype are called carcinogens, and the process is carcinogenesis. A gene, protein, cell or organism that has been altered by mutation is called a mutant.

Mutation is considered a stochastic (statistically random) process. That is, the probability of mutation at a given locus is independent of the environment in which an organism lives: advantageous mutations cannot be induced by the environment. Mutation proceeds regardless of whether it is beneficial, harmful, or neutral to the organism. However, there is a constraint on the randomness of the process: mutations that prevent the development of an organism in the first place do not ever surface phenotypically for obvious reasons.

Mutation is the key driving force in evolution, and mutations within a population are acted upon by other forces such as natural selection, gene flow and genetic drift.


Point mutations (also substitutions) are mutations that alter only one base in the DNA sequence. They may be transitions, where a purine is replaced by another purine (or the same for a pyrimidine): for instance a G to A mutation. Alternatively they may be transversions, where a purine is replaced by a pyrimidine or vice versa: for instance a G to C mutation. Transitions are more common than transversions, since purines and pyrimidines are structurally distinct so the substitution of one for another has a significant steric effect on the DNA helix which is more easily recognised by the proof-reading machinery.

Point mutations, whether transitions or transversions, have no effect on the reading frame of the sequence.

Point mutations can be further classified according to their direct impact on the protein product:

  • Silent mutations (also synonymous mutations) are base changes that have no effect on the amino acid coded for. This is due to the degeneracy of the genetic code

  • Neutral mutations are base changes that substitute an amino acid for a different amino acid, but one of similar chemical properties. For instance, an AAA-AGA point mutation results in an arginine-lysine amino acid substitution. Since both these amino acids are positively charged (basic), it is likely that this change in amino acid will have no significant effect on the protein product

  • Missense mutations (also non-synonymous mutations) are base changes that substitute an amino acid for a different amino acid, of different chemical properties. These may or may not be deleterious (harmful) depending on their impact on the protein product

  • Nonsense mutations are base changes that substitute an amino acid-coding codon with a premature stop codon (TGA, TAG or TAA). This leads to premature termination of polypeptide translation and, depending on how prematurely the stop codon is inserted, may be deleterious or neutral in its effect

Frame-shift mutations are mutations that involve the removal or addition of one or more base(s), and a subsequent shift in the reading frame of the DNA sequence (i.e. the triplet codons are rearranged). This can be highly deleterious if the mutation occurs early on in the sequence, but even at later intervals may still be harmful.

Another way to classify mutations is by their effect on gene function. The broad categories for such mutations are loss-of-function mutation and gain-of-function mutation. These categories may be further divided: for instance, a neomorphic mutation is a gain-of-function mutation that creates an allele with an entirely novel function.

Mutations may also occur at a level above the nucleotide sequence; such mutations alter the structure or number of chromosomes in a cell. These mutations are called chromosomal aberrations, and may include inversions, translocations, deletions and duplications leading either to gene amplification or polyploidisation. As with other mutations, chromosomal aberrations may serve to drive evolution, but often are deleterious to the host organism.


Mutation may be caused by a wide range of factors. Perhaps the most obvious one is errors in DNA replication. The enzyme DNA polymerase which catalyses the replication of DNA to produce new cells has an error rate of approximately 1 in every 10 million bases. In the human genome (with a haploid genome of 3,000 million bases) this equates to 300 mistakes made per new cell synthesised (note however that DNA polymerase has an error-checking ability so this figure is drastically reduced in practice). Nonetheless, random errors in DNA replication may result in mutagenesis and mutant daughter cells. Errors in DNA replication occur because the organism has to trade-off speed with accuracy. Trying to say the following tongue-twister, with a time limit, may help to illustrate this point:

“I’m not the pheasant plucker,

I’m the pheasant plucker’s mate

and I’m only plucking pheasants

‘cause the pheasant plucker’s late

Other biological causes of mutation may include the action of transposons, retrotransposons or certain viruses.

Physical agents which may lead to mutation include X-rays and ionizing radiation, as caused by gamma and ultraviolet (UV) rays. X-rays can break the phosphodiester bonds that constitute the sugar-phosphate backbone of DNA, resulting in deletions or recombinations. Meanwhile gamma and UV rays may cause dimerisation of adjacent pyrimidines - in particular ultraviolet radiation results in the formation of thymine dimers.

Chemical modifications of bases may lead to mutation. For instance, deamination of cytosine residues results in the formation of uracil . Because uracil is not usually found in DNA, this is usually quickly corrected. However, in eukaryotes especially, cytosine residues are often methylated . Methylated cytosine residues are deaminated to produce thymine. These mutations are less well-noticed by the proofreading mechanisms since thymine is a common component of DNA, and often a CG pairing will be replaced by a TA pairing as the result of deamination. Depurination is another chemical process, this time involving the removal of purine bases. Once a purine base is removed, it can be replaced by any base randomly chosen by the proofreading mechanism. This means that there is a 1 in 4 chance that there will be no consequence, but a 3 in 4 chance of mutation.