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Mutations can involve the duplication of large sections of DNA, usually through genetic recombination.[5] These duplications are a major source of raw material for evolving new genes, with tens to hundreds of genes duplicated in animal genomes every million years.[6] Most genes belong to larger families of genes of shared ancestry.[7] Novel genes are produced by several methods, commonly through the duplication and mutation of an ancestral gene, or by recombining parts of different genes to form new combinations with new functions.[8][9]

Here, domains act as modules, each with a particular and independent function, that can be mixed together to produce genes encoding new proteins with novel properties.[10] For example, the human eye uses four genes to make structures that sense light: three for color vision and one for night vision; all four arose from a single ancestral gene.[11] Another advantage of duplicating a gene (or even an entire genome) is that this increases redundancy; this allows one gene in the pair to acquire a new function while the other copy performs the original function.[12][13] Other types of mutation occasionally create new genes from previously noncoding DNA.[14][15]


Sequences of DNA that can move about the genome, such as transposons, make up a major fraction of the genetic material of plants and animals, and may have been important in the evolution of genomes.[18] For example, more than a million copies of the Alu sequence are present in the human genome, and these sequences have now been recruited to perform functions such as regulating gene expression.[19] Another effect of these mobile DNA sequences is that when they move within a genome, they can mutate or delete existing genes and thereby produce genetic diversity.[2]

Nonlethal mutations accumulate within the gene pool and increase the amount of genetic variation.[20] The abundance of some genetic changes within the gene pool can be reduced by natural selection, while other "more favorable" mutations may accumulate and result in adaptive changes.



Beneficial mutations can improve reproductive success.


Main article: Mutagenesis

Four classes of mutations are (1) spontaneous mutations (molecular decay), (2) mutations due to error prone replication by-pass of naturally occurring DNA damage (also called error prone translesion synthesis), (3) errors introduced during DNA repair, and (4) induced mutations caused by mutagens. Scientists may also deliberately introduce mutant sequences through DNA manipulation for the sake of scientific experimentation.

Spontaneous mutation[edit]

Spontaneous mutations on the molecular level can be caused by:[21]


Error prone replication by-pass[edit]

There is increasing evidence that the majority of spontaneously arising mutations are due to error prone replication (translesion synthesis) past a DNA damage in the template strand. As described in the article DNA damage (naturally occurring), naturally occurring DNA damages arise about 60,000 to 100,000 times per day per mammalian cell. In mice, the majority of mutations are caused by translesion synthesis.[22] Likewise, in yeast, Kunz et al.[23] found that more than 60% of the spontaneous single base pair substitutions and deletions were caused by translesion synthesis.

Errors introduced during DNA repair[edit]

Although naturally occurring double-strand breaks occur at a relatively low frequency in DNA (see DNA damage (naturally occurring)) their repair often causes mutation. Non-homologous end joining (NHEJ) is a major pathway for repairing double-strand breaks. NHEJ involves removal of a few nucleotides to allow somewhat inaccurate alignment of the two ends for rejoining followed by addition of nucleotides to fill in gaps. As a consequence, NHEJ often introduces mutations.[24]

A covalent adduct between benzo[a]pyrene, the major mutagen in tobacco smoke, and DNA[25]

Induced mutation[edit]

Induced mutations on the molecular level can be caused by:-

  • Chemicals
    • Hydroxylamine NH
    • Base analogs (e.g., BrdU)
    • Alkylating agents (e.g., N-ethyl-N-nitrosourea) These agents can mutate both replicating and non-replicating DNA. In contrast, a base analog can mutate the DNA only when the analog is incorporated in replicating the DNA. Each of these classes of chemical mutagens has certain effects that then lead to transitions, transversions, or deletions.
    • Agents that form DNA adducts (e.g., ochratoxin A metabolites)[26]
    • DNA intercalating agents (e.g., ethidium bromide)
    • DNA crosslinkers
    • Oxidative damage
  • Radiation
    • Ultraviolet radiation (nonionizing radiation). Two nucleotide bases in DNA — cytosine and thymine — are most vulnerable to radiation that can change their properties. UV light can induce adjacent pyrimidine bases in a DNA strand to become covalently joined as a pyrimidine dimer. UV radiation, in particular longer-wave UVA, can also cause oxidative damage to DNA.[27]

Classification of mutation types[edit]

By effect on structure[edit]

Illustrations of five types of chromosomal mutations.
Selection of disease-causing mutations, in a standard table of the genetic code of amino acids.[28]


  • Large-scale mutations in chromosomal structure, including:
      • Chromosomal translocations: interchange of genetic parts from nonhomologous chromosomes.
      • Chromosomal inversions: reversing the orientation of a chromosomal segment.
    • Loss of heterozygosity: loss of one allele, either by a deletion or a recombination event, in an organism that previously had two different alleles.

By effect on function[edit]

  • Dominant negative mutations (also called antimorphic mutations) have an altered gene product that acts antagonistically to the wild-type allele. These mutations usually result in an altered molecular function (often inactive) and are characterized by a dominant or semi-dominant phenotype. In humans, dominant negative mutations have been implicated in cancer (e.g., mutations in genes p53,[31] ATM,[32] CEBPA[33] and PPARgamma[34]). It was once thought that Marfan syndrome is an example of a the occurrence of a dominant negative mutation in an autosomal-dominant disease where the defective glycoprotein product of the fibrillin gene (FBN1) antagonizes the product of the normal allele. However, it may appear this is not that case and that Marfan's may be a result of haploinsufficiency due to the absence of one normal allele that causes the disease not the presence of an abnormal allele (i.e., Dominant negative).[citation needed]

See also Behavior mutation.

By effect on fitness[edit]


  • A neutral mutation has no harmful or beneficial effect on the organism. Such mutations occur at a steady rate, forming the basis for the molecular clock. In the neutral theory of molecular evolution, neutral mutations provide genetic drift is the basis for most variation at the molecular level.

Distribution of fitness effects[edit]

In reality, viewing the fitness effects of mutations in these discrete categories is an oversimplification. Attempts have been made to infer the distribution of fitness effects (DFE) using mutagenesis experiments and theoretical models applied to molecular sequence data. Distribution of fitness effects, as used to determine the relative abundance of different types of mutations (i.e., strongly deleterious, nearly neutral or advantageous), is relevant to many evolutionary questions, such as the maintenance of genetic variation,[36] the rate of genomic decay,[37] the maintenance of outcrossing sexual reproduction as opposed to inbreeding[38] and the evolution of sex and recombination.[39] In summary, DFE plays an important role in predicting evolutionary dynamics.[40][41] A variety of approaches have been used to study the distribution of fitness effects, including theoretical, experimental and analytical methods.

  • Mutagenesis experiment: The direct method to investigate DFE is to induce mutations and then measure the mutational fitness effects, which has already been done in viruses, bacteria, yeast, and Drosophila. For example, most studies of DFE in viruses used site-directed mutagenesis to create point mutations and measure relative fitness of each mutant.[42][43][44][45] In Escherichia coli, one study used transposon mutagenesis to directly measure the fitness of a random insertion of a derivative of Tn10.[46] In yeast, a combined mutagenesis and deep sequencing approach has been developed to generate high-quality systematic mutant libraries and measure fitness in high throughput.[47] However, given that many mutations have effects too small to be detected[48] and that mutagenesis experiments can detect only mutations of moderately large effect; DNA sequence data analysis can provide valuable information about these mutations.
  • Molecular sequence analysis: With rapid development of DNA sequencing technology, an enormous amount of DNA sequence data is available and even more is forthcoming in the future. Various methods have been developed to infer DFE from DNA sequence data.[49][50][51][52] By examining DNA sequence differences within and between species, we are able to infer various characteristics of the DFE for neutral, deleterious and advantageous mutations.[20] To be specific, the DNA sequence analysis approach allows us to estimate the effects of mutations with very small effects, which are hardly detectable through mutagenesis experiments.

One of the earliest theoretical studies of the distribution of fitness effects was done by Motoo Kimura, an influential theoretical population geneticist. His neutral theory of molecular evolution proposes that most novel mutations will be highly deleterious, with a small fraction being neutral.[53][54] Hiroshi Akashi more recently proposed a bimodal model for DFE, with modes centered around highly deleterious and neutral mutations.[55] Both theories agree that the vast majority of novel mutations are neutral or deleterious and that advantageous mutations are rare, which has been supported by experimental results. One example is a study done on the distribution of fitness effects of random mutations in vesicular stomatitis virus.[42] Out of all mutations, 39.6% were lethal, 31.2% were non-lethal deleterious, and 27.1% were neutral. Another example comes from a high throughput mutagenesis experiment with yeast.[47] In this experiment it was shown that the overall distribution of fitness effects is bimodal, with a cluster of neutral mutations, and a broad distribution of deleterious mutations.

Though relatively few mutations are advantageous, those that are play an important role in evolutionary changes.[56] Like neutral mutations, weakly selected advantageous mutations can be lost due to random genetic drift, but strongly selected advantageous mutations are more likely to be fixed. Knowing the distribution of fitness effects of advantageous mutations may lead to increased ability to predict the evolutionary dynamics. Theoretical work on the DFE for advantageous mutations has been done by John H. Gillespie[57] and H. Allen Orr.[58] They proposed that the distribution for advantageous mutations should be exponential under a wide range of conditions, which, in general, has been supported by experimental studies, at least for strongly selected advantageous mutations.[59][60][61]


By impact on protein sequence[edit]


By inheritance[edit]


In multicellular organisms with dedicated reproductive cells, mutations can be subdivided into germ line mutations, which can be passed on to descendants through their reproductive cells, and somatic mutations (also called acquired mutations),[63] which involve cells outside the dedicated reproductive group and which are not usually transmitted to descendants.


The distinction between germline and somatic mutations is important in animals that have a dedicated germ line to produce reproductive cells. However, it is of little value in understanding the effects of mutations in plants, which lack dedicated germ line. The distinction is also blurred in those animals that reproduce asexually through mechanisms such as budding, because the cells that give rise to the daughter organisms also give rise to that organisms germ line. A new mutation that was not inherited from either parent is called a de novo mutation.


  • A heterozygous mutation is a mutation of only one allele.
  • Compound heterozygous mutations or a genetic compound comprises two different mutations in the paternal and maternal alleles.[65]


Special classes[edit]





Mutation rates[edit]

Further information: Mutation rate


According to one study, two children of different parents had 35 and 49 new mutations. Of them, in one case 92% were from the paternal germline, in another case, 64% were from the maternal germline.[67]

Harmful mutations[edit]


If a mutation is present in a germ cell, it can give rise to offspring that carries the mutation in all of its cells. This is the case in hereditary diseases. In particular, if there is a mutation in a DNA repair gene within a germ cell, humans carrying such germ-line mutations may have an increased risk of cancer. A list of 34 such germ-line mutations is given in the article DNA repair-deficiency disorder. On the other hand, a mutation may occur in a somatic cell of an organism. Such mutations will be present in all descendants of this cell within the same organism, and certain mutations can cause the cell to become malignant, and, thus, cause cancer.[69]


Beneficial mutations[edit]

Although mutations that cause change in protein sequences can be harmful to an organism; on occasions, the effect may be positive in a given environment. In this case, the mutation may enable the mutant organism to withstand particular environmental stresses better than wild-type organisms, or reproduce more quickly. In these cases a mutation will tend to become more common in a population through natural selection.

For example, a specific 32 base pair deletion in human CCR5 (CCR5-Δ32) confers HIV resistance to homozygotes and delays AIDS onset in heterozygotes.[70] One possible explanation of the etiology of the relatively high frequency of CCR5-Δ32 in the European population is that it conferred resistance to the bubonic plague in mid-14th century Europe. People with this mutation were more likely to survive infection; thus its frequency in the population increased.[71] This theory could explain why this mutation is not found in southern Africa, which remained untouched by bubonic plague. A newer theory suggests that the selective pressure on the CCR5 Delta 32 mutation was caused by smallpox instead of the bubonic plague.[72]

Another example is Sickle-cell disease, a blood disorder in which the body produces an abnormal type of the oxygen-carrying substance hemoglobin in the red blood cells. One-third of all indigenous inhabitants of Sub-Saharan Africa carry the gene,[73] because, in areas where malaria is common, there is a survival value in carrying only a single sickle-cell gene (sickle-cell trait).[74] Those with only one of the two alleles of the sickle-cell disease are more resistant to malaria, since the infestation of the malaria plasmodium is halted by the sickling of the cells that it infests.

Prion mutations[edit]


Somatic mutations[edit]

See also: Carcinogenesis




See also[edit]


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