Editing Gene duplication (section)

==As an evolutionary event==
[[File:Evolution fate duplicate genes - vector.svg|thumb|right|400px|Evolutionary fate of duplicate genes]]

=== Rate of gene duplication ===
Comparisons of genomes demonstrate that gene duplications are common in most species investigated. This is indicated by variable copy numbers ([[copy number variation]]) in the genome of humans<ref>{{cite journal | vauthors = Sebat J, Lakshmi B, Troge J, Alexander J, Young J, Lundin P, Månér S, Massa H, Walker M, Chi M, Navin N, Lucito R, Healy J, Hicks J, Ye K, Reiner A, Gilliam TC, Trask B, Patterson N, Zetterberg A, Wigler M | display-authors = 6 | title = Large-scale copy number polymorphism in the human genome | journal = Science | volume = 305 | issue = 5683 | pages = 525–8 | date = July 2004 | pmid = 15273396 | doi = 10.1126/science.1098918 | bibcode = 2004Sci...305..525S | s2cid = 20357402 }}</ref><ref>{{cite journal | vauthors = Iafrate AJ, Feuk L, Rivera MN, Listewnik ML, Donahoe PK, Qi Y, Scherer SW, Lee C | display-authors = 6 | title = Detection of large-scale variation in the human genome | journal = Nature Genetics | volume = 36 | issue = 9 | pages = 949–51 | date = September 2004 | pmid = 15286789 | doi = 10.1038/ng1416 | doi-access = free }}</ref> or fruit flies.<ref>{{cite journal | vauthors = Emerson JJ, Cardoso-Moreira M, Borevitz JO, Long M | title = Natural selection shapes genome-wide patterns of copy-number polymorphism in Drosophila melanogaster | journal = Science | volume = 320 | issue = 5883 | pages = 1629–31 | date = June 2008 | pmid = 18535209 | doi = 10.1126/science.1158078 | bibcode = 2008Sci...320.1629E | s2cid = 206512885 }}</ref> However, it has been difficult to measure the rate at which such duplications occur. Recent studies yielded a first direct estimate of the genome-wide rate of gene duplication in ''[[Caenorhabditis elegans|C. elegans]]'', the first multicellular eukaryote for which such as estimate became available. The gene duplication rate in ''C. elegans'' is on the order of 10<sup>−7</sup> duplications/gene/generation, that is, in a population of 10 million worms, one will have a gene duplication per generation. This rate is two orders of magnitude greater than the spontaneous rate of point mutation per nucleotide site in this species.<ref>{{cite journal | vauthors = Lipinski KJ, Farslow JC, Fitzpatrick KA, Lynch M, Katju V, Bergthorsson U | title = High spontaneous rate of gene duplication in Caenorhabditis elegans | journal = Current Biology | volume = 21 | issue = 4 | pages = 306–10 | date = February 2011 | pmid = 21295484 | pmc = 3056611 | doi = 10.1016/j.cub.2011.01.026 | bibcode = 2011CBio...21..306L }}</ref> Older (indirect) studies reported locus-specific duplication rates in bacteria, ''Drosophila'', and humans ranging from 10<sup>−3</sup> to 10<sup>−7</sup>/gene/generation.<ref>{{cite journal | vauthors = Anderson P, Roth J | title = Spontaneous tandem genetic duplications in Salmonella typhimurium arise by unequal recombination between rRNA (rrn) cistrons | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 78 | issue = 5 | pages = 3113–7 | date = May 1981 | pmid = 6789329 | pmc = 319510 | doi = 10.1073/pnas.78.5.3113 | bibcode = 1981PNAS...78.3113A | doi-access = free }}</ref><ref>{{cite journal | vauthors = Watanabe Y, Takahashi A, Itoh M, Takano-Shimizu T | title = Molecular spectrum of spontaneous de novo mutations in male and female germline cells of Drosophila melanogaster | journal = Genetics | volume = 181 | issue = 3 | pages = 1035–43 | date = March 2009 | pmid = 19114461 | pmc = 2651040 | doi = 10.1534/genetics.108.093385 }}</ref><ref>{{cite journal | vauthors = Turner DJ, Miretti M, Rajan D, Fiegler H, Carter NP, Blayney ML, Beck S, Hurles ME | display-authors = 6 | title = Germline rates of de novo meiotic deletions and duplications causing several genomic disorders | journal = Nature Genetics | volume = 40 | issue = 1 | pages = 90–5 | date = January 2008 | pmid = 18059269 | pmc = 2669897 | doi = 10.1038/ng.2007.40 }}</ref>

===Neofunctionalization===

{{Main|Neofunctionalization}}

Gene duplications are an essential source of genetic novelty that can lead to evolutionary innovation. Duplication creates genetic redundancy, where the second copy of the gene is often free from [[purifying selection|selective pressure]]—that is, [[mutation]]s of it have no deleterious effects to its host organism.  If one copy of a gene experiences a mutation that affects its original function, the second copy can serve as a 'spare part' and continue to function correctly.  Thus, duplicate genes accumulate mutations faster than a functional single-copy gene, over generations of organisms, and it is possible for one of the two copies to develop a new and different function. Some examples of such neofunctionalization is the apparent mutation of a duplicated digestive gene in a family of [[Notothenioidei|ice fish]] into an antifreeze gene and duplication leading to a novel snake venom gene<ref name=VLynch>{{cite journal | vauthors = Lynch VJ | title = Inventing an arsenal: adaptive evolution and neofunctionalization of snake venom phospholipase A2 genes | journal = BMC Evolutionary Biology | volume = 7 | pages = 2 | date = January 2007 | pmid = 17233905 | pmc = 1783844 | doi = 10.1186/1471-2148-7-2 | doi-access = free }}</ref> and the synthesis of 1 beta-hydroxytestosterone in pigs.<ref name=Conant>{{cite journal | vauthors = Conant GC, Wolfe KH | title = Turning a hobby into a job: how duplicated genes find new functions | journal = Nature Reviews. Genetics | volume = 9 | issue = 12 | pages = 938–50 | date = December 2008 | pmid = 19015656 | doi = 10.1038/nrg2482 | s2cid = 1240225 }}</ref>

Gene duplication is believed to play a major role in [[evolution]]; this stance has been held by members of the scientific community for over 100 years.<ref name="Taylor_Raes_2004">{{cite journal | vauthors = Taylor JS, Raes J | title = Duplication and divergence: the evolution of new genes and old ideas | journal = Annual Review of Genetics | volume = 38 | pages = 615–43 | year = 2004 | pmid = 15568988 | doi = 10.1146/annurev.genet.38.072902.092831 }}</ref> [[Susumu Ohno]] was one of the most famous developers of this theory in his classic book ''Evolution by gene duplication'' (1970).<ref name="Ohno_1970">{{cite book |last=Ohno |first=S. |year=1970 |title=Evolution by gene duplication|publisher=[[Springer Science+Business Media|Springer-Verlag]]| isbn=978-0-04-575015-3 |author-link=Susumu Ohno}}</ref>  Ohno argued that gene duplication is the most important evolutionary force since the emergence of the [[common descent|universal common ancestor]].<ref name="Ohno_1967">{{cite book |last=Ohno |first=S. |year=1967 |title=Sex Chromosomes and Sex-linked Genes|url=https://archive.org/details/sexchromosomesse0001ohno |url-access=registration |publisher=Springer-Verlag |isbn=978-91-554-5776-1 }}</ref>
Major [[Polyploidy|genome duplication]] events can be quite common. It is believed that the entire [[yeast]] [[genome]] underwent duplication about 100 million years ago.<ref name="Kellis_2004">{{cite journal | vauthors = Kellis M, Birren BW, Lander ES | title = Proof and evolutionary analysis of ancient genome duplication in the yeast Saccharomyces cerevisiae | journal = Nature | volume = 428 | issue = 6983 | pages = 617–24 | date = April 2004 | pmid = 15004568 | doi = 10.1038/nature02424 | bibcode = 2004Natur.428..617K | s2cid = 4422074 }}</ref>  [[Plant]]s are the most prolific genome duplicators.  For example, [[wheat]] is hexaploid (a kind of [[polyploid]]), meaning that it has six copies of its genome.

===Subfunctionalization===

{{Main|Subfunctionalization}}

Another possible fate for duplicate genes is that both copies are equally free to accumulate degenerative mutations, so long as any defects are complemented by the other copy. This leads to a neutral "[[subfunctionalization]]" (a process of [[constructive neutral evolution]]) or DDC (duplication-degeneration-complementation) model,<ref name=Force_1999>{{cite journal | vauthors = Force A, Lynch M, Pickett FB, Amores A, Yan YL, Postlethwait J | title = Preservation of duplicate genes by complementary, degenerative mutations | journal = Genetics | volume = 151 | issue = 4 | pages = 1531–45 | date = April 1999 | doi = 10.1093/genetics/151.4.1531 | pmid = 10101175 | pmc = 1460548 }}</ref><ref name=Stoltzfus_1999>{{cite journal | vauthors = Stoltzfus A | title = On the possibility of constructive neutral evolution | journal = Journal of Molecular Evolution | volume = 49 | issue = 2 | pages = 169–81 | date = August 1999 | pmid = 10441669 | doi = 10.1007/PL00006540 | citeseerx = 10.1.1.466.5042 | bibcode = 1999JMolE..49..169S | s2cid = 1743092 }}</ref> in which the functionality of the original gene is distributed among the two copies.  Neither gene can be lost, as both now perform important non-redundant functions, but ultimately neither is able to achieve novel functionality.

Subfunctionalization can occur through neutral processes in which mutations accumulate with no detrimental or beneficial effects.  However, in some cases subfunctionalization can occur with clear adaptive benefits.  If an ancestral gene is [[pleiotropy|pleiotropic]] and performs two functions, often neither one of these two functions can be changed without affecting the other function.  In this way, partitioning the ancestral functions into two separate genes can allow for adaptive specialization of subfunctions, thereby providing an adaptive benefit.<ref name=DesMerais>{{cite journal | vauthors = Des Marais DL, Rausher MD | title = Escape from adaptive conflict after duplication in an anthocyanin pathway gene | journal = Nature | volume = 454 | issue = 7205 | pages = 762–5 | date = August 2008 | pmid = 18594508 | doi = 10.1038/nature07092 | bibcode = 2008Natur.454..762D | s2cid = 418964 }}</ref>

===Loss===
Often the resulting genomic variation leads to gene dosage dependent neurological disorders such as [[Rett syndrome|Rett-like syndrome]] and [[Pelizaeus–Merzbacher disease]].<ref>{{cite journal | vauthors = Lee JA, Lupski JR | title = Genomic rearrangements and gene copy-number alterations as a cause of nervous system disorders | journal = Neuron | volume = 52 | issue = 1 | pages = 103–21 | date = October 2006 | pmid = 17015230 | doi = 10.1016/j.neuron.2006.09.027 | s2cid = 22412305 | doi-access = free }}</ref>  Such detrimental mutations are likely to be lost from the population and will not be preserved or develop novel functions. However, many duplications are, in fact, not detrimental or beneficial, and these neutral sequences may be lost or may spread through the population through random fluctuations via [[genetic drift]].