Editing Mutation rate (section)

==Variation in mutation rates==

[[File:Molecular evolution bamboos.svg|thumb|250px|right|alt=Phylogram showing three groups, one of which has strikingly longer branches than the two others|[[Generation time]] affects mutation rates: The long-lived woody bamboos (tribes [[Arundinarieae]] and [[Bambuseae]]) have lower mutation rates (short branches in the [[phylogenetic tree]]) than the fast-evolving herbaceous bamboos ([[Olyreae]]).]]

Mutation rates differ between species and even between different regions of the genome of a single species. Mutation rates can also differ even between genotypes of the same species; for example, bacteria have been observed to evolve hypermutability as they adapt to new selective conditions.<ref>{{cite journal | vauthors = Wielgoss S, Barrick JE, Tenaillon O, Wiser MJ, Dittmar WJ, Cruveiller S, Chane-Woon-Ming B, Médigue C, Lenski RE, Schneider D | title = Mutation rate dynamics in a bacterial population reflect tension between adaptation and genetic load | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 110 | issue = 1 | pages = 222–227 | date = January 2013 | pmid = 23248287 | pmc = 3538217 | doi = 10.1073/pnas.1219574110 | doi-access = free | bibcode = 2013PNAS..110..222W }}</ref> These different rates of nucleotide substitution are measured in substitutions ([[Fixation (population genetics)|fixed mutations]]) per base pair per generation. For example, mutations in intergenic, or non-coding, DNA tend to accumulate at a faster rate than mutations in DNA that is actively in use in the organism ([[gene expression]]). That is not necessarily due to a higher mutation rate, but to lower levels of [[purifying selection]]. A region which mutates at predictable rate is a candidate for use as a [[molecular clock]].

If the rate of neutral mutations in a sequence is assumed to be constant (clock-like), and if most differences between species are neutral rather than adaptive, then the number of differences between two different species can be used to estimate how long ago two species diverged (see [[molecular clock]]). In fact, the mutation rate of an organism may change in response to environmental stress. For example, UV light damages DNA, which may result in error prone attempts by the cell to perform [[DNA repair]].

The human mutation rate is higher in the male germ line (sperm) than the female (egg cells), but estimates of the exact rate have varied by an order of magnitude or more. This means that a human genome accumulates around 64 new mutations per generation because each full generation involves a number of cell divisions to generate gametes.<ref name="Genetics">{{cite journal | vauthors = Drake JW, Charlesworth B, Charlesworth D, Crow JF | title = Rates of spontaneous mutation | journal = Genetics | volume = 148 | issue = 4 | pages = 1667–1686 | date = April 1998 | pmid = 9560386 | pmc = 1460098 | doi = 10.1093/genetics/148.4.1667 | url = http://www.genetics.org/cgi/content/full/148/4/1667 | access-date = 2007-09-27 | url-status = live | archive-url = https://web.archive.org/web/20100821100757/http://www.genetics.org/cgi/content/full/148/4/1667 | archive-date = 2010-08-21 }}</ref> Human mitochondrial DNA has been estimated to have mutation rates of ~3× or ~2.7×10<sup>&minus;5</sup> per base per 20 year generation (depending on the method of estimation);<ref>{{cite journal | vauthors = Schneider S, Excoffier L | title = Estimation of past demographic parameters from the distribution of pairwise differences when the mutation rates vary among sites: application to human mitochondrial DNA | journal = Genetics | volume = 152 | issue = 3 | pages = 1079–1089 | date = July 1999 | pmid = 10388826 | pmc = 1460660 | doi = 10.1093/genetics/152.3.1079 | url = http://www.genetics.org/cgi/reprint/152/3/1079 | access-date = 2008-02-25 | url-status = live | archive-url = https://web.archive.org/web/20080908074904/http://www.genetics.org/cgi/reprint/152/3/1079 | archive-date = 2008-09-08 }}</ref> these rates are considered to be significantly higher than rates of human genomic mutation at ~2.5×10<sup>&minus;8</sup> per base per generation.<ref name="Nachman">{{cite journal | vauthors = Nachman MW, Crowell SL | title = Estimate of the mutation rate per nucleotide in humans | journal = Genetics | volume = 156 | issue = 1 | pages = 297–304 | date = September 2000 | pmid = 10978293 | pmc = 1461236 | doi = 10.1093/genetics/156.1.297 | url = http://www.genetics.org/cgi/content/full/156/1/297 | access-date = 2007-10-19 | url-status = live | archive-url = https://web.archive.org/web/20110408213817/http://www.genetics.org/cgi/content/full/156/1/297 | archive-date = 2011-04-08 }}</ref> Using data available from whole genome sequencing, the human genome mutation rate is similarly estimated to be ~1.1×10<sup>&minus;8</sup> per site per generation.<ref name="Science">{{cite journal | vauthors = Roach JC, Glusman G, Smit AF, Huff CD, Hubley R, Shannon PT, Rowen L, Pant KP, Goodman N, Bamshad M, Shendure J, Drmanac R, Jorde LB, Hood L, Galas DJ | title = Analysis of genetic inheritance in a family quartet by whole-genome sequencing | journal = Science | volume = 328 | issue = 5978 | pages = 636–639 | date = April 2010 | pmid = 20220176 | pmc = 3037280 | doi = 10.1126/science.1186802 | bibcode = 2010Sci...328..636R }}</ref>

The rate for other forms of mutation also differs greatly from [[point mutations]]. An individual [[Microsatellite (genetics)|microsatellite]] locus often has a mutation rate on the order of 10<sup>&minus;4</sup>, though this can differ greatly with length.<ref>{{cite journal | vauthors = Whittaker JC, Harbord RM, Boxall N, Mackay I, Dawson G, Sibly RM | title = Likelihood-based estimation of microsatellite mutation rates | journal = Genetics | volume = 164 | issue = 2 | pages = 781–787 | date = June 2003 | pmid = 12807796 | pmc = 1462577 | doi = 10.1093/genetics/164.2.781 | url = http://www.genetics.org/content/164/2/781.full | access-date = 2011-05-03 | url-status = live | archive-url = https://web.archive.org/web/20111128184524/http://www.genetics.org/content/164/2/781.full | archive-date = 2011-11-28 }}</ref>

Some sequences of DNA may be more susceptible to mutation. For example, stretches of DNA in human sperm which lack methylation are more prone to mutation.<ref>{{cite web | vauthors = Gravtiz L |title=Lack of DNA modification creates hotspots for mutations |date=28 June 2012 |publisher=Simons Foundation Autism Research Initiative |url=http://sfari.org/news-and-opinion/news/2012/lack-of-dna-modification-creates-hotspots-for-mutations |access-date=20 February 2014 |archive-date=5 March 2014 |archive-url=https://web.archive.org/web/20140305134537/http://sfari.org/news-and-opinion/news/2012/lack-of-dna-modification-creates-hotspots-for-mutations |url-status=live }}</ref>

In general, the mutation rate in unicellular [[eukaryotes]] (and [[bacteria]]) is roughly 0.003 mutations per genome per ''cell'' generation.<ref name="Genetics" /> However, some species, especially the [[ciliate]] of the genus ''[[Paramecium]]'' have an unusually low mutation rate. For instance, ''Paramecium tetraurelia'' has a base-substitution mutation rate of ~2 × 10<sup>−11</sup> per site per cell division. This is the lowest mutation rate observed in nature so far, being about 75× lower than in other eukaryotes with a similar genome size, and even 10× lower than in most prokaryotes. The low mutation rate in ''Paramecium'' has been explained by its transcriptionally silent [[Germline|germ-line]] [[Cell nucleus|nucleus]], consistent with the hypothesis that replication fidelity is higher at lower [[gene expression]] levels.<ref>{{cite journal | vauthors = Sung W, Tucker AE, Doak TG, Choi E, Thomas WK, Lynch M | title = Extraordinary genome stability in the ciliate Paramecium tetraurelia | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 109 | issue = 47 | pages = 19339–19344 | date = November 2012 | pmid = 23129619 | pmc = 3511141 | doi = 10.1073/pnas.1210663109 | doi-access = free | bibcode = 2012PNAS..10919339S }}</ref>

The highest per base pair per generation mutation rates are found in viruses, which can have either RNA or DNA genomes. DNA viruses have mutation rates between 10<sup>&minus;6</sup> to 10<sup>&minus;8</sup> mutations per base per generation, and RNA viruses have mutation rates between 10<sup>&minus;3</sup> to 10<sup>&minus;5</sup> per base per generation.<ref name="Genetics" />