Editing Mutation rate (section)

==Evolution==
The theory on the evolution of mutation rates identifies three principal forces involved: the generation of more deleterious mutations with higher mutation, the generation of more advantageous mutations with higher mutation, and the metabolic costs and reduced replication rates that are required to prevent mutations. Different conclusions are reached based on the relative importance attributed to each force. The optimal mutation rate of organisms may be determined by a trade-off between costs of a high mutation rate,<ref name=Altenberg>{{cite journal | vauthors = Altenberg L | title = An evolutionary reduction principle for mutation rates at multiple Loci | journal = Bulletin of Mathematical Biology | volume = 73 | issue = 6 | pages = 1227–1270 | date = June 2011 | pmid = 20737227 | doi = 10.1007/s11538-010-9557-9 | arxiv = 0909.2454 | s2cid = 15027684 }}</ref> such as deleterious mutations, and the [[metabolism|metabolic]] costs of maintaining systems to reduce the mutation rate (such as increasing the expression of DNA repair enzymes.<ref name=Sniegowski>{{cite journal | vauthors = Sniegowski PD, Gerrish PJ, Johnson T, Shaver A | title = The evolution of mutation rates: separating causes from consequences | journal = BioEssays | volume = 22 | issue = 12 | pages = 1057–1066 | date = December 2000 | pmid = 11084621 | doi = 10.1002/1521-1878(200012)22:12<1057::AID-BIES3>3.0.CO;2-W | s2cid = 36771934 }}</ref> or, as reviewed by Bernstein et al.<ref>{{cite book |vauthors=Bernstein H, Hopf FA, Michod RE |title=Molecular Genetics of Development |chapter=The molecular basis of the evolution of sex |series=Advances in Genetics |volume=24 |pages=323–70 |year=1987 |pmid=3324702 |doi=10.1016/s0065-2660(08)60012-7 |isbn=9780120176243}}</ref> having increased energy use for repair, coding for additional gene products and/or having slower replication). Secondly, higher mutation rates increase the rate of beneficial mutations, and evolution may prevent a lowering of the mutation rate in order to maintain optimal rates of adaptation.<ref name=Orr>{{cite journal | vauthors = Orr HA | title = The rate of adaptation in asexuals | journal = Genetics | volume = 155 | issue = 2 | pages = 961–968 | date = June 2000 | pmid = 10835413 | pmc = 1461099 | doi = 10.1093/genetics/155.2.961 | url = http://www.genetics.org/cgi/pmidlookup?view=long&pmid=10835413 | access-date = 2014-11-01 | url-status = live | archive-url = https://web.archive.org/web/20220625052242/https://academic.oup.com/genetics | archive-date = 2022-06-25 }}</ref><ref>{{Cite journal |last1=Wielgoss |first1=S |last2=Barrick |first2=JE |last3=Tenaillon |first3=O |last4=Wiser |first4=MJ |last5=Dittmar |first5=WJ |last6=Cruvellier |first6=S |last7=Chane-Moon-Wing |first7=B |last8=Médigue |first8=C |last9=Lenski |first9=RE |last10=Schneider |first10=D |date=November 13, 2012 |title=Mutation rate dynamics in a bacterial population reflect tension between adaptation and genetic load |url=https://www.pnas.org/doi/abs/10.1073/pnas.1219574110 |journal=Proceedings of the National Academy of Sciences, USA |volume=110 |pages=222–227 |doi=10.1073/pnas.12195741|doi-broken-date=1 November 2024 |doi-access=free }}</ref> As such, hypermutation enables some cells to rapidly adapt to changing conditions in order to avoid the entire population from becoming extinct.<ref>{{cite journal | vauthors = Swings T, Van den Bergh B, Wuyts S, Oeyen E, Voordeckers K, Verstrepen KJ, Fauvart M, Verstraeten N, Michiels J | title = Adaptive tuning of mutation rates allows fast response to lethal stress in <i>Escherichia coli</i> | journal = eLife | volume = 6 | date = May 2017 | pmid = 28460660 | pmc = 5429094 | doi = 10.7554/eLife.22939 | doi-access = free }}</ref> Finally, natural selection may fail to optimize the mutation rate because of the relatively minor benefits of lowering the mutation rate, and thus the observed mutation rate is the product of neutral processes.<ref name=Lynch_1>{{cite journal | vauthors = Lynch M | title = Evolution of the mutation rate | journal = Trends in Genetics | volume = 26 | issue = 8 | pages = 345–352 | date = August 2010 | pmid = 20594608 | pmc = 2910838 | doi = 10.1016/j.tig.2010.05.003 }}</ref><ref name=Sung_1>{{cite journal | vauthors = Sung W, Ackerman MS, Miller SF, Doak TG, Lynch M | title = Drift-barrier hypothesis and mutation-rate evolution | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 109 | issue = 45 | pages = 18488–18492 | date = November 2012 | pmid = 23077252 | pmc = 3494944 | doi = 10.1073/pnas.1216223109 | doi-access = free | bibcode = 2012PNAS..10918488S }}</ref>

Studies have shown that treating [[RNA virus]]es such as [[poliovirus]] with [[ribavirin]] produce results consistent with the idea that the viruses mutated too frequently to maintain the integrity of the information in their genomes.<ref name="Crotty">{{cite journal | vauthors = Crotty S, Cameron CE, Andino R | title = RNA virus error catastrophe: direct molecular test by using ribavirin | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 98 | issue = 12 | pages = 6895–6900 | date = June 2001 | pmid = 11371613 | pmc = 34449 | doi = 10.1073/pnas.111085598 | doi-access = free | bibcode = 2001PNAS...98.6895C }}</ref> This is termed [[error catastrophe]].

The characteristically high mutation rate of [[HIV]] (Human Immunodeficiency Virus) of 3 x 10<sup>−5</sup> per base and generation, coupled with its short replication cycle leads to a high [[antigen]] variability, allowing it to evade the immune system.<ref name="Rambaut_2004">{{cite journal | vauthors = Rambaut A, Posada D, Crandall KA, Holmes EC | title = The causes and consequences of HIV evolution | journal = Nature Reviews. Genetics | volume = 5 | issue = 1 | pages = 52–61 | date = January 2004 | pmid = 14708016 | doi = 10.1038/nrg1246 | url = http://tree.bio.ed.ac.uk/downloadPaper.php?id=242 | access-date = 2019-05-28 | url-status = live | s2cid = 5790569 | doi-access = free | archive-url = https://web.archive.org/web/20191109035127/http://tree.bio.ed.ac.uk/downloadPaper.php?id=242 | archive-date = 2019-11-09 }}</ref>