Editing Gene duplication

{{Short description|Duplication of a gene sequence within a genome}}
'''Gene duplication''' (or '''chromosomal duplication''' or '''     gene amplification''') is a major mechanism through which new genetic material is generated during [[molecular evolution]]. It can be defined as any duplication of a region of [[DNA]] that contains a [[gene]].  Gene duplications can arise as products of several types of errors in [[DNA replication]] and [[DNA repair|repair]] machinery as well as through fortuitous capture by selfish genetic elements.  Common sources of gene duplications include [[ectopic recombination]],  [[retrotransposon|retrotransposition]] event, [[aneuploidy]], [[polyploidy]], and [[replication slippage]].<ref name="Zhang_2003">{{cite journal |author=Zhang J |title=Evolution by gene duplication: an update |journal=Trends in Ecology & Evolution |volume=18 |issue=6 |pages=292–8 |year=2003 |doi=10.1016/S0169-5347(03)00033-8 |url=http://www.umich.edu/~zhanglab/publications/2003/Zhang_2003_TIG_18_292.pdf }}</ref>

==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.

==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]].

==Identifying duplications in sequenced genomes==

===Criteria and single genome scans===
The two genes that exist after a gene duplication event are called [[Paralog#Orthology and paralogy|paralogs]] and usually code for [[protein]]s with a similar function and/or structure.  By contrast, [[Paralog#Orthology and paralogy|orthologous]] genes present in different species which are each originally derived from the same ancestral sequence.  (See [[Homology (biology)#Sequence homology|Homology of sequences in genetics]]).

It is important (but often difficult) to differentiate between paralogs and orthologs in biological research. Experiments on human gene function can often be carried out on other [[species]] if a homolog to a human gene can be found in the genome of that species, but only if the homolog is orthologous. If they are paralogs and resulted from a gene duplication event, their functions are likely to be too different. One or more copies of duplicated genes that constitute a gene family may be affected by insertion of [[transposable elements]] that causes significant variation between them in their sequence and finally may become responsible for [[divergent evolution]]. This may also render the chances and the rate of [[gene conversion]] between the homologs of gene duplicates due to less or no similarity in their sequences.

Paralogs can be identified in single genomes through a sequence comparison of all annotated gene models to one another.  Such a comparison can be performed on translated amino acid sequences (e.g. BLASTp, tBLASTx) to identify ancient duplications or on DNA nucleotide sequences (e.g. BLASTn, megablast) to identify more recent duplications.  Most studies to identify gene duplications require reciprocal-best-hits or fuzzy reciprocal-best-hits, where each paralog must be the other's single best match in a sequence comparison.<ref name= Hahn>{{cite journal | vauthors = Hahn MW, Han MV, Han SG | title = Gene family evolution across 12 Drosophila genomes | journal = PLOS Genetics | volume = 3 | issue = 11 | pages = e197 | date = November 2007 | pmid = 17997610 | pmc = 2065885 | doi = 10.1371/journal.pgen.0030197 | doi-access = free }}</ref>

Most gene duplications exist as [[low copy repeats]] (LCRs), rather highly repetitive sequences like transposable elements. They are mostly found in [[Chromosome regions|pericentronomic]], [[subtelomeric]] and [[Chromosome regions|interstitial]] regions of a chromosome. Many LCRs, due to their size (>1Kb), similarity, and orientation, are highly susceptible to duplications and deletions.

===Genomic microarrays detect duplications===
Technologies such as genomic [[microarrays]], also called array comparative [[genomic]] hybridization (array CGH), are used to detect chromosomal abnormalities, such as microduplications, in a high throughput fashion from genomic DNA samples. In particular, DNA [[microarray]] technology can simultaneously monitor the [[gene expression|expression]] levels of thousands of genes across many  treatments or experimental conditions, greatly facilitating the evolutionary studies of [[gene regulation]] after gene duplication or [[speciation]].<ref>{{cite journal | vauthors = Mao R, Pevsner J | title = The use of genomic microarrays to study chromosomal abnormalities in mental retardation | journal = Mental Retardation and Developmental Disabilities Research Reviews | volume = 11 | issue = 4 | pages = 279–85 | year = 2005 | pmid = 16240409 | doi = 10.1002/mrdd.20082 }}</ref><ref>{{cite journal | vauthors = Gu X, Zhang Z, Huang W | title = Rapid evolution of expression and regulatory divergences after yeast gene duplication | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 102 | issue = 3 | pages = 707–12 | date = January 2005 | pmid = 15647348 | pmc = 545572 | doi = 10.1073/pnas.0409186102 | bibcode = 2005PNAS..102..707G | doi-access = free }}</ref>

===Next generation sequencing===
Gene duplications can also be identified through the use of next-generation sequencing platforms.  The simplest means to identify duplications in genomic resequencing data is through the use of paired-end sequencing reads.  Tandem duplications are indicated by sequencing read pairs which map in abnormal orientations.  Through a combination of increased sequence coverage and abnormal mapping orientation, it is possible to identify duplications in genomic sequencing data.

==Nomenclature==
[[File:Human karyotype with bands and sub-bands.png|thumb|300px|Human [[karyotype]] with annotated bands and sub-bands as used for the nomenclature of chromosome abnormalities. It shows dark and white regions as seen on [[G banding]]. Each row is vertically aligned at [[centromere]] level. It shows 22 [[Homologous chromosome|homologous]] [[autosomal]] chromosome pairs, both the female (XX) and male (XY) versions of the two [[sex chromosome]]s, as well as the [[human mitochondrial genetics|mitochondrial genome]] (at bottom left). {{further|Karyotype}}]]
The [[International System for Human Cytogenomic Nomenclature]] (ISCN) is an international standard for [[human chromosome]] [[nomenclature]], which includes band names, symbols and abbreviated terms used in the description of human chromosome and chromosome abnormalities. Abbreviations include ''dup'' for duplications of parts of a chromosome.<ref>{{cite web|url=https://www.coriell.org/0/sections/support/global/iscn_help.aspx?PgId=263|title=ISCN Symbols and Abbreviated Terms|website=Coriell Institute for Medical Research|accessdate=2022-10-27}}</ref> For example, dup(17p12) causes [[Charcot–Marie–Tooth disease]] type 1A.<ref>{{cite web|url=https://omim.org/entry/118220?search=118220&highlight=118220|title=HARCOT-MARIE-TOOTH DISEASE, DEMYELINATING, TYPE 1A; CMT1A|website=[[OMIM]]|author=Cassandra L. Kniffin}} Updated : 4/23/2014</ref>

==As amplification==
Gene duplication does not necessarily constitute a lasting change in a species' genome.  In fact, such changes often don't last past the initial host organism.  From the perspective of [[molecular genetics]], [[gene amplification]] is one of many ways in which a [[gene]] can be [[Gene expression#Overexpression|overexpressed]].  Genetic amplification can occur artificially, as with the use of the [[polymerase chain reaction]] technique to amplify short strands of [[DNA]] ''[[in vitro]]'' using [[enzymes]], or it can occur naturally, as described above.  If it's a natural duplication, it can still take place in a [[somatic cell]], rather than a [[germline]] cell (which would be necessary for a lasting evolutionary change).

===Role in cancer===
Duplications of [[oncogenes]] are a common cause of many types of [[cancer]]. In such cases the genetic duplication occurs in a somatic cell and affects only the genome of the cancer cells themselves, not the entire organism, much less any subsequent offspring. Recent comprehensive patient-level classification and quantification of driver events in [[The Cancer Genome Atlas|TCGA]] cohorts revealed that there are on average 12 driver events per tumor, of which 1.5 are amplifications of oncogenes.<ref>{{cite journal |last1=Vyatkin |first1=Alexey D. |last2=Otnyukov |first2=Danila V. |last3=Leonov |first3=Sergey V. |last4=Belikov |first4=Aleksey V. |title=Comprehensive patient-level classification and quantification of driver events in TCGA PanCanAtlas cohorts |journal=PLOS Genetics |date=14 January 2022 |volume=18 |issue=1 |pages=e1009996 |doi=10.1371/journal.pgen.1009996|pmid=35030162 |pmc=8759692 |doi-access=free }}</ref>

{|class="wikitable"
|+Common oncogene amplifications in human cancers
|-
! Cancer type !! Associated gene<br> amplifications !! Prevalence of <br>amplification <br>in cancer type<br> (percent)
|-
|rowspan=5| [[Breast cancer]] || [[MYC]] || 20%<ref name=Vogelstein2002>{{cite book |last1=Kinzler |first1=Kenneth W. |last2=Vogelstein |first2=Bert | name-list-style = vanc |title=The genetic basis of human cancer |publisher=McGraw-Hill |year=2002 |page=116 |isbn=978-0-07-137050-9 |url=https://books.google.com/books?id=pYG09OPbXp0C&pg=PA116 }}</ref>
|-
| [[ERBB2]] ([[HER2]]) || 20%<ref name=Vogelstein2002/>
|-
| [[CCND1]] ([[Cyclin D1]]) || 15–20%<ref name=Vogelstein2002/>
|-
| [[FGFR1]] || 12%<ref name=Vogelstein2002/>
|-
| [[FGFR2]] ||  12%<ref name=Vogelstein2002/>
|-
|rowspan=2| [[Cervical cancer]] || [[MYC]] || 25–50%<ref name=Vogelstein2002/>
|-
| [[ERBB2]] || 20%<ref name=Vogelstein2002/>
|-
|rowspan=3| [[Colorectal cancer]] || [[HRAS]] || 30%<ref name=Vogelstein2002/>
|-
| [[KRAS]] || 20%<ref name=Vogelstein2002/>
|-
| [[MYB (gene)|MYB]] || 15–20%<ref name=Vogelstein2002/>
|-
|rowspan=3| [[Esophageal cancer]] || [[MYC]] || 40%<ref name=Vogelstein2002/>
|-
| [[CCND1]] || 25%<ref name=Vogelstein2002/>
|-
| [[MDM2]] || 13%<ref name=Vogelstein2002/>
|-
|rowspan=3| [[Gastric cancer]] || [[Cyclin E|CCNE]] ([[Cyclin E]]) || 15%<ref name=Vogelstein2002/>
|-
| [[KRAS]] || 10%<ref name=Vogelstein2002/>
|-
| [[C-Met|MET]] || 10%<ref name=Vogelstein2002/>
|-
|rowspan=2| [[Glioblastoma]] || [[epidermal growth factor receptor|ERBB1]] ([[epidermal growth factor receptor|EGFR]]) || 33–50%<ref name=Vogelstein2002/>
|-
| [[CDK4]] || 15%<ref name=Vogelstein2002/>
|-
|rowspan=3| [[Head and neck cancer]] || [[CCND1]] || 50%<ref name=Vogelstein2002/>
|-
| [[epidermal growth factor receptor|ERBB1]] || 10%<ref name=Vogelstein2002/>
|-
| [[MYC]] || 7–10%<ref name=Vogelstein2002/>
|-
| [[Hepatocellular cancer]] || [[CCND1]] || 13%<ref name=Vogelstein2002/>
|-
| [[Neuroblastoma]] || [[MYCN]] || 20–25%<ref name=Vogelstein2002/>
|-
|rowspan=3| [[Ovarian cancer]] || [[MYC]] || 20–30%<ref name=Vogelstein2002/>
|-
| [[ERBB2]] || 15–30%<ref name=Vogelstein2002/>
|-
| [[AKT2]] || 12%<ref name=Vogelstein2002/>
|-
|rowspan=2| [[Sarcoma]] || [[MDM2]] || 10–30%<ref name=Vogelstein2002/>
|-
| [[CDK4]] || 10%<ref name=Vogelstein2002/>
|-
| [[Small cell lung cancer]] || [[MYC]] || 15–20%<ref name=Vogelstein2002/>
|-
|}


Whole-genome duplications are also frequent in cancers, detected in 30% to 36% of tumors from the most common cancer types.<ref>{{Cite journal |last1=Bielski |first1=Craig M. |last2=Zehir |first2=Ahmet |last3=Penson |first3=Alexander V. |last4=Donoghue |first4=Mark T. A. |last5=Chatila |first5=Walid |last6=Armenia |first6=Joshua |last7=Chang |first7=Matthew T. |last8=Schram |first8=Alison M. |last9=Jonsson |first9=Philip |last10=Bandlamudi |first10=Chaitanya |last11=Razavi |first11=Pedram |last12=Iyer |first12=Gopa |last13=Robson |first13=Mark E. |last14=Stadler |first14=Zsofia K. |last15=Schultz |first15=Nikolaus |date=2018 |title=Genome doubling shapes the evolution and prognosis of advanced cancers |journal=Nature Genetics |language=en |volume=50 |issue=8 |pages=1189–1195 |doi=10.1038/s41588-018-0165-1 |pmid=30013179 |issn=1546-1718|pmc=6072608 }}</ref><ref>{{Cite journal |last1=Quinton |first1=Ryan J. |last2=DiDomizio |first2=Amanda |last3=Vittoria |first3=Marc A. |last4=Kotýnková |first4=Kristýna |last5=Ticas |first5=Carlos J. |last6=Patel |first6=Sheena |last7=Koga |first7=Yusuke |last8=Vakhshoorzadeh |first8=Jasmine |last9=Hermance |first9=Nicole |last10=Kuroda |first10=Taruho S. |last11=Parulekar |first11=Neha |last12=Taylor |first12=Alison M. |last13=Manning |first13=Amity L. |last14=Campbell |first14=Joshua D. |last15=Ganem |first15=Neil J. |date=2021 |title=Whole-genome doubling confers unique genetic vulnerabilities on tumour cells |journal=Nature |language=en |volume=590 |issue=7846 |pages=492–497 |doi=10.1038/s41586-020-03133-3 |pmid=33505027 |issn=1476-4687|pmc=7889737 |bibcode=2021Natur.590..492Q }}</ref> Their exact role in carcinogenesis is unclear, but they in some cases lead to loss of chromatin segregation leading to chromatin conformation changes that in turn lead to oncogenic epigenetic and transcriptional modifications.<ref>{{Cite journal |last1=Lambuta |first1=Ruxandra A. |last2=Nanni |first2=Luca |last3=Liu |first3=Yuanlong |last4=Diaz-Miyar |first4=Juan |last5=Iyer |first5=Arvind |last6=Tavernari |first6=Daniele |last7=Katanayeva |first7=Natalya |last8=Ciriello |first8=Giovanni |last9=Oricchio |first9=Elisa |date=2023-03-15 |title=Whole-genome doubling drives oncogenic loss of chromatin segregation |journal=Nature |volume=615 |issue=7954 |language=en |pages=925–933 |doi=10.1038/s41586-023-05794-2 |issn=1476-4687|doi-access=free |pmid=36922594 |pmc=10060163 |bibcode=2023Natur.615..925L }}</ref> 

== See also ==
{{cmn|
* [[Comparative genomics]]
* [[DbDNV]] (2010)
* [[De novo gene birth]]
* [[Exon shuffling]]
* [[Gene amplification in Paramecium tetraurelia]]
* [[Fusion gene|Gene fusion]]
* [[Horizontal gene transfer]]
* [[Human genome]]
* [[Inparanoid]]
* [[Mobile genetic elements]]
* [[Molecular evolution]]
* [[Pseudogene]]
* [[Tandem exon duplication]]
* [[Unequal crossing over]]
}}

== References ==
{{reflist}}

== External links ==
* [https://web.archive.org/web/20120831220744/http://www.nslij-genetics.org/duplication/ ''A bibliography on gene and genome duplication'']
* [https://web.archive.org/web/20140222212135/http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/M/Mutations.html#duplications ''A brief overview of mutation, gene duplication and translocation'']

{{MolecularEvolution|state=expanded}}
{{Repeated sequence}}
{{Self-replicating organic structures}}

{{DEFAULTSORT:Gene Duplication}}
[[Category:Evolutionary biology concepts]]
[[Category:Genetics concepts]]
[[Category:Modification of genetic information]]
[[Category:Molecular evolution]]
[[Category:Mutation]]