Editing Mutation (section)

== Mutation rates ==
{{Further|Mutation rate|Critical mutation rate}}
[[Mutation rate]]s vary substantially across species, and the evolutionary forces that generally determine mutation are the subject of ongoing investigation.

In '''humans''', the [[mutation rate]] is about 50–90 ''de novo'' mutations per genome per generation, that is, each human accumulates about 50–90 novel mutations that were not present in his or her parents. This number has been established by [[DNA sequencing|sequencing]] thousands of human trios, that is, two parents and at least one child.<ref>{{cite journal | vauthors = Jónsson H, Sulem P, Kehr B, Kristmundsdottir S, Zink F, Hjartarson E, Hardarson MT, Hjorleifsson KE, Eggertsson HP, Gudjonsson SA, Ward LD, Arnadottir GA, Helgason EA, Helgason H, Gylfason A, Jonasdottir A, Jonasdottir A, Rafnar T, Frigge M, Stacey SN, Th Magnusson O, Thorsteinsdottir U, Masson G, Kong A, Halldorsson BV, Helgason A, Gudbjartsson DF, Stefansson K | display-authors = 6 | title = Parental influence on human germline de novo mutations in 1,548 trios from Iceland | journal = Nature | volume = 549 | issue = 7673 | pages = 519–522 | date = September 2017 | pmid = 28959963 | doi = 10.1038/nature24018 | s2cid = 205260431 | bibcode = 2017Natur.549..519J }}</ref>

The genomes of [[RNA virus]]es are based on [[RNA]] rather than DNA. The RNA viral genome can be double-stranded (as in DNA) or single-stranded. In some of these viruses (such as the single-stranded [[HIV|human immunodeficiency virus]]), replication occurs quickly, and there are no mechanisms to check the genome for accuracy. This error-prone process often results in mutations.

The rate of de novo mutations, whether germline or somatic, vary among organisms.<ref>{{cite journal |last1=Bromham |first1=Lindell |title=WHy do species very in their rate of molecular evolution? |date=2009 |volume=5 |issue=3 |pages=401–404 |journal=Biology Letters |doi=10.1098/rsbl.2009.0136 |pmid=19364710 |pmc=2679939 }}</ref> Individuals within the same species can even express varying rates of mutation.<ref name="The population genetics of mutation">{{cite journal |last1=Loewe |first1=Laurence |last2=Hill |first2=William G. |title=The population genetics of mutations: good, bad, and indifferent |journal=Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences |date=2010 |volume=365 |issue=1544 |pages=1153–1167 |publisher=Philosophical transactions of the Royal Society of London |doi=10.1098/rstb.2009.0317 |pmid=20308090 |pmc=2871823 }}</ref> Overall, rates of de novo mutations are low compared to those of inherited mutations, which categorizes them as rare forms of [[genetic variation]].<ref>{{cite journal |last1=Mohiuddin |first1=Mohiuddin |last2=Kooy |first2=R. Frank |last3=Pearson |first3=Christopher E. |title=DE novo mutations, genetic mosaicism, and genetic disease |journal=Frontiers in Genetics |date=2022 |volume=13 |doi=10.3389/fgene.2022.983668 |doi-access=free |pmid=36226191 |pmc=9550265 }}</ref> Many observations of de novo mutation rates have associated higher rates of mutation correlated to paternal age. In sexually reproducing organisms, the comparatively higher frequency of cell divisions in the parental sperm donor germline drive conclusions that rates of de novo mutation can be tracked along a common basis. The frequency of error during the DNA replication process of [[gametogenesis]], especially amplified in the rapid production of sperm cells, can promote more opportunities for de novo mutations to replicate unregulated by DNA repair machinery.<ref>{{cite journal |last1=Mohiuddin |first1=Mohiuddin |last2=Kooy |first2=R. Frank |last3=Pearson |first3=Christopher E. |title=De novo mutations, genetic mosaicism, and genetic disease |journal=Frontiers in Genetics |date=2022 |volume=13 |doi=10.3389/fgene.2022.983668 |doi-access=free |pmid=36226191 |pmc=9550265 }}</ref> This claim combines the observed effects of increased probability for mutation in rapid [[spermatogenesis]] with short periods of time between cellular divisions that limit the efficiency of repair machinery.<ref>{{cite journal |last1=Acuna-Hidalgo |first1=Rocio |last2=Veltman |first2=Joris A. |last3=Hoischen |first3=Alexander |title=New insights into the generation and role of de novo mutations in health and disease |date=2016 |journal=Genome Biology |volume=17 |issue=1 |page=241 |doi=10.1186/s13059-016-1110-1 |doi-access=free |pmid=27894357 |pmc=5125044 }}</ref> Rates of de novo mutations that affect an organism during its development can also increase with certain environmental factors. For example, certain intensities of exposure to radioactive elements can inflict damage to an organism's genome, heightening rates of mutation. In humans, the appearance of [[skin cancer]] during one's lifetime is induced by overexposure to [[UV radiation]] that causes mutations in the cellular and skin genome.<ref>{{cite journal |last1=Ikehata |first1=Hironobu |last2=Ono |first2=Tetsuya |title=The mechanisms of UV mutagenesis |url=https://pubmed.ncbi.nlm.nih.gov/21436607/ |journal=Journal of Radiation Research |date=2011 |volume=52 |issue=2 |pages=115–125 |publisher=J Radiat Res |doi=10.1269/jrr.10175 |pmid=21436607 |bibcode=2011JRadR..52..115I |access-date=9 December 2023}}</ref>

=== Randomness of mutations ===
There is a widespread assumption that mutations are (entirely) "random" with respect to their consequences (in terms of probability). This was shown to be wrong as mutation frequency can vary across regions of the genome, with such [[DNA repair]]- and mutation-biases being associated with various factors. For instance, Monroe and colleagues demonstrated that—in the studied plant (''Arabidopsis thaliana'')—more important genes mutate less frequently than less important ones. They demonstrated that mutation is "non-random in a way that benefits the plant".<ref>{{cite news |title=Study challenges evolutionary theory that DNA mutations are random |url=https://phys.org/news/2022-01-evolutionary-theory-dna-mutations-random.html |access-date=12 February 2022 |work=[[U.C. Davis]] |language=en}}</ref><ref>{{cite journal | vauthors = Monroe JG, Srikant T, Carbonell-Bejerano P, Becker C, Lensink M, Exposito-Alonso M, Klein M, Hildebrandt J, Neumann M, Kliebenstein D, Weng ML, Imbert E, Ågren J, Rutter MT, Fenster CB, Weigel D | display-authors = 6 | title = Mutation bias reflects natural selection in Arabidopsis thaliana | journal = Nature | volume = 602 | issue = 7895 | pages = 101–105 | date = February 2022 | pmid = 35022609 | pmc = 8810380 | doi = 10.1038/s41586-021-04269-6 | bibcode = 2022Natur.602..101M }}</ref> Additionally, previous experiments typically used to demonstrate mutations being random with respect to fitness (such as the [[Fluctuation Test]] and [[Replica plating]]) have been shown to only support the weaker claim that those mutations are random with respect to external selective constraints, not fitness as a whole.<ref>{{cite journal |doi=10.1007/s10441-023-09464-8 |author=Bartlett, J. |title=Random with Respect to Fitness or External Selection? An Important but Often Overlooked Distinction |journal=Acta Biotheoretica |volume=71 |issue=2 |date=2023 |page=12 |pmid=36933070 |s2cid=257585761 }}</ref>