Editing Gene duplication (section)

==Mechanisms of duplication==

===Ectopic recombination===
Duplications arise from an event termed [[unequal crossing-over]] that occurs during meiosis between misaligned homologous chromosomes. The chance of it happening is a function of the degree of sharing of repetitive elements between two chromosomes. The products of this recombination are a duplication at the site of the exchange and a reciprocal deletion. Ectopic recombination is typically mediated by sequence similarity at the duplicate breakpoints, which form direct repeats.  Repetitive genetic elements such as [[transposable]] elements offer one source of repetitive DNA that can facilitate recombination, and they are often found at duplication breakpoints in plants and mammals.<ref>{{cite web |title=Definition of Gene duplication |date=2012-03-19 |work=medterms medical dictionary |publisher=MedicineNet |url=http://www.medterms.com/script/main/art.asp?articlekey=3562 |access-date=2008-12-01 |archive-date=2014-03-06 |archive-url=https://web.archive.org/web/20140306214736/http://www.medterms.com/script/main/art.asp?articlekey=3562 |url-status=dead }}</ref>
[[Image:gene-duplication.png|thumb|200px|Schematic of a region of a chromosome before and after a duplication event]]

===Replication slippage===
[[Replication slippage]] is an error in DNA replication that can produce duplications of short genetic sequences.  During replication [[DNA polymerase]] begins to copy the DNA.  At some point during the replication process, the polymerase dissociates from the DNA and replication stalls.  When the polymerase reattaches to the DNA strand, it aligns the replicating strand to an incorrect position and incidentally copies the same section more than once.  Replication slippage is also often facilitated by repetitive sequences, but requires only a few bases of similarity.{{Citation needed|date=February 2023}}

===Retrotransposition===
[[Retrotransposon]]s, mainly [[LINE1|L1]], can occasionally act on cellular mRNA. Transcripts are reverse transcribed to DNA and inserted into random place in the genome, creating retrogenes.  Resulting sequence usually lack introns and often contain poly(A) sequences that are also integrated into the genome. Many retrogenes display changes in gene regulation in comparison to their parental gene sequences, which sometimes results in novel functions. Retrogenes can move between different chromosomes to shape chromosomal evolution.<ref>{{Cite journal |last1=Miller |first1=Duncan |last2=Chen |first2=Jianhai |last3=Liang |first3=Jiangtao |last4=Betrán |first4=Esther |last5=Long |first5=Manyuan |last6=Sharakhov |first6=Igor V. |date=2022-05-28 |title=Retrogene Duplication and Expression Patterns Shaped by the Evolution of Sex Chromosomes in Malaria Mosquitoes |journal=Genes |volume=13 |issue=6 |pages=968 |doi=10.3390/genes13060968 |issn=2073-4425 |pmc=9222922 |pmid=35741730 |doi-access=free }}</ref>

===Aneuploidy===
[[Aneuploidy]] occurs when nondisjunction at a single chromosome results in an abnormal number of chromosomes. Aneuploidy is often harmful and in mammals regularly leads to spontaneous abortions (miscarriages).  Some aneuploid individuals are viable, for example trisomy 21 in humans, which leads to [[Down syndrome]].  Aneuploidy often alters gene dosage in ways that are detrimental to the organism; therefore, it is unlikely to spread through populations.

===Polyploidy===
[[Polyploidy]], or ''whole genome duplication'', is a product of [[nondisjunction]] during meiosis which results in additional copies of the entire genome.  Polyploidy is common in plants, but it has also occurred in animals, with two rounds of whole genome duplication ([[2R hypothesis|2R event]]) in the vertebrate lineage leading to humans.<ref name="HollandDehal2005">{{cite journal | vauthors = Dehal P, Boore JL | title = Two rounds of whole genome duplication in the ancestral vertebrate | journal = PLOS Biology | volume = 3 | issue = 10 | pages = e314 | date = October 2005 | pmid = 16128622 | pmc = 1197285 | doi = 10.1371/journal.pbio.0030314 | doi-access = free }}</ref> It has also occurred in the hemiascomycete yeasts ~100 mya.<ref>{{Cite journal|last1=Wolfe|first1=K. H.|last2=Shields|first2=D. C.|date=1997-06-12|title=Molecular evidence for an ancient duplication of the entire yeast genome|journal=Nature|volume=387|issue=6634|pages=708–713|doi=10.1038/42711|issn=0028-0836|pmid=9192896|bibcode=1997Natur.387..708W|s2cid=4307263|doi-access=free}}</ref><ref>{{Cite journal|last1=Kellis|first1=Manolis|last2=Birren|first2=Bruce W.|last3=Lander|first3=Eric S.|date=2004-04-08|title=Proof and evolutionary analysis of ancient genome duplication in the yeast Saccharomyces cerevisiae|url=https://pubmed.ncbi.nlm.nih.gov/15004568|journal=Nature|volume=428|issue=6983|pages=617–624|doi=10.1038/nature02424|issn=1476-4687|pmid=15004568|bibcode=2004Natur.428..617K|s2cid=4422074}}</ref>

After a whole genome duplication, there is a relatively short period of genome instability, extensive gene loss, elevated levels of nucleotide substitution and regulatory network rewiring.<ref>{{Cite journal|last=Otto|first=Sarah P.|date=2007-11-02|title=The evolutionary consequences of polyploidy|journal=Cell|volume=131|issue=3|pages=452–462|doi=10.1016/j.cell.2007.10.022|issn=0092-8674|pmid=17981114|s2cid=10054182|doi-access=free}}</ref><ref>{{Cite journal|last1=Conant|first1=Gavin C.|last2=Wolfe|first2=Kenneth H.|date=April 2006|title=Functional partitioning of yeast co-expression networks after genome duplication|journal=PLOS Biology|volume=4|issue=4|pages=e109|doi=10.1371/journal.pbio.0040109|issn=1545-7885|pmc=1420641|pmid=16555924 |doi-access=free }}</ref>  In addition, gene dosage effects play a significant role.<ref>{{Cite journal|last1=Papp|first1=Balázs|last2=Pál|first2=Csaba|last3=Hurst|first3=Laurence D.|date=2003-07-10|title=Dosage sensitivity and the evolution of gene families in yeast|url=https://pubmed.ncbi.nlm.nih.gov/12853957|journal=Nature|volume=424|issue=6945|pages=194–197|doi=10.1038/nature01771|issn=1476-4687|pmid=12853957|bibcode=2003Natur.424..194P|s2cid=4382441}}</ref> Thus, most duplicates are lost within a short period, however, a considerable fraction of duplicates survive.<ref>{{Cite journal|last1=Lynch|first1=M.|last2=Conery|first2=J. S.|date=2000-11-10|title=The evolutionary fate and consequences of duplicate genes|url=https://pubmed.ncbi.nlm.nih.gov/11073452|journal=Science|volume=290|issue=5494|pages=1151–1155|doi=10.1126/science.290.5494.1151|issn=0036-8075|pmid=11073452|bibcode=2000Sci...290.1151L}}</ref>  Interestingly, genes involved in regulation are preferentially retained.<ref>{{Cite journal|last1=Freeling|first1=Michael|last2=Thomas|first2=Brian C.|date=July 2006|title=Gene-balanced duplications, like tetraploidy, provide predictable drive to increase morphological complexity|journal=Genome Research|volume=16|issue=7|pages=805–814|doi=10.1101/gr.3681406|issn=1088-9051|pmid=16818725|doi-access=free}}</ref><ref>{{Cite journal|last1=Davis|first1=Jerel C.|last2=Petrov|first2=Dmitri A.|date=October 2005|title=Do disparate mechanisms of duplication add similar genes to the genome?|url=https://pubmed.ncbi.nlm.nih.gov/16098632|journal=Trends in Genetics |volume=21|issue=10|pages=548–551|doi=10.1016/j.tig.2005.07.008|issn=0168-9525|pmid=16098632}}</ref> Furthermore, retention of regulatory genes, most notably the [[Hox gene]]s, has led to adaptive innovation.

Rapid evolution and functional divergence have been observed at the level of the transcription of duplicated genes, usually by point mutations in short transcription factor binding motifs.<ref>{{Cite journal|last1=Casneuf|first1=Tineke|last2=De Bodt|first2=Stefanie|last3=Raes|first3=Jeroen|last4=Maere|first4=Steven|last5=Van de Peer|first5=Yves|date=2006|title=Nonrandom divergence of gene expression following gene and genome duplications in the flowering plant Arabidopsis thaliana|journal=Genome Biology|volume=7|issue=2|pages=R13|doi=10.1186/gb-2006-7-2-r13|issn=1474-760X|pmc=1431724|pmid=16507168 |doi-access=free }}</ref><ref>{{Cite journal|last1=Li|first1=Wen-Hsiung|last2=Yang|first2=Jing|last3=Gu|first3=Xun|date=November 2005|title=Expression divergence between duplicate genes|url=https://pubmed.ncbi.nlm.nih.gov/16140417|journal=Trends in Genetics |volume=21|issue=11|pages=602–607|doi=10.1016/j.tig.2005.08.006|issn=0168-9525|pmid=16140417}}</ref> Furthermore, rapid evolution of protein phosphorylation motifs, usually embedded within rapidly evolving intrinsically disordered regions is another contributing factor for survival and rapid adaptation/neofunctionalization of duplicate genes.<ref name=":0">{{Cite journal|last1=Amoutzias|first1=Grigoris D.|last2=He|first2=Ying|last3=Gordon|first3=Jonathan|last4=Mossialos|first4=Dimitris|last5=Oliver|first5=Stephen G.|last6=Van de Peer|first6=Yves|date=2010-02-16|title=Posttranslational regulation impacts the fate of duplicated genes|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=107|issue=7|pages=2967–2971|doi=10.1073/pnas.0911603107|issn=1091-6490|pmc=2840353|pmid=20080574|bibcode=2010PNAS..107.2967A|doi-access=free}}</ref> Thus, a link seems to exist between gene regulation (at least at the post-translational level) and genome evolution.<ref name=":0" />

Polyploidy is also a well known source of speciation, as offspring, which have different numbers of chromosomes compared to parent species, are often unable to interbreed with non-polyploid organisms.  Whole genome duplications are thought to be less detrimental than aneuploidy as the relative dosage of individual genes should be the same.