Duplication and retention biases of essential and non-essential genes revealed by systematic knockdown analyses

dc.contributor.authorWoods, Shane
dc.contributor.authorCoghlan, Avril
dc.contributor.authorRivers, David
dc.contributor.authorWarnecke, Tobias
dc.contributor.authorJeffries, Sean J.
dc.contributor.authorKwon, Taejoon
dc.contributor.authorRogers, Anthony
dc.contributor.authorHurst, Laurence D.
dc.contributor.authorAhringer, Julie
dc.contributor.funderGates Cambridge Scholarship programmeen
dc.contributor.funderRoyal Society, United Kingdomen
dc.contributor.funderWellcome Trust, United Kingdomen
dc.contributor.funderWissenschaftskolleg zu Berlinde
dc.contributor.funderNational Institutes of Health, United Statesen
dc.date.accessioned2016-02-17T11:46:18Z
dc.date.available2016-02-17T11:46:18Z
dc.date.issued2013
dc.description.abstractWhen a duplicate gene has no apparent loss-of-function phenotype, it is commonly considered that the phenotype has been masked as a result of functional redundancy with the remaining paralog. This is supported by indirect evidence showing that multi-copy genes show loss-of-function phenotypes less often than single-copy genes and by direct tests of phenotype masking using select gene sets. Here we take a systematic genome-wide RNA interference approach to assess phenotype masking in paralog pairs in the Caenorhabditis elegans genome. Remarkably, in contrast to expectations, we find that phenotype masking makes only a minor contribution to the low knockdown phenotype rate for duplicate genes. Instead, we find that non-essential genes are highly over-represented among duplicates, leading to a low observed loss-of-function phenotype rate. We further find that duplicate pairs derived from essential and non-essential genes have contrasting evolutionary dynamics: whereas non-essential genes are both more often successfully duplicated (fixed) and lost, essential genes are less often duplicated but upon successful duplication are maintained over longer periods. We expect the fundamental evolutionary duplication dynamics presented here to be broadly applicable.en
dc.description.sponsorshipGates Cambridge Scholarship; Royal Society Wolfson Research Merit Award; Wellcome Trust Senior Research Fellowship (054523); Wellcome Trust; Wissenschaftskolleg zu Berlin; MRC; NIH National Center for Research Resources (NCRR)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.articleidUNSP e1003330
dc.identifier.citationWoods S, Coghlan A, Rivers D, Warnecke T, Jeffries SJ, Kwon T, et al. (2013) Duplication and Retention Biases of Essential and Non-Essential Genes Revealed by Systematic Knockdown Analyses. PLoS Genet 9(5): e1003330. doi:10.1371/journal.pgen.1003330en
dc.identifier.doi10.1371/journal.pgen.1003330
dc.identifier.issn1553-7390
dc.identifier.issued5en
dc.identifier.journaltitlePLOS GENETICSen
dc.identifier.urihttps://hdl.handle.net/10468/2381
dc.identifier.volume9en
dc.language.isoenen
dc.publisherPublic Library of Scienceen
dc.rights© 2013 Woods et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are crediteden
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectC. elegans chromosome-Ien
dc.subjectCaenorhabditis elegansen
dc.subjectRNA interferenceen
dc.subjectPhylogenetic treesen
dc.subjectCopy numberen
dc.subjectC. elegansen
dc.subjectYeasten
dc.subjectRedundancyen
dc.subjectEvolutionen
dc.subjectFamiliesen
dc.titleDuplication and retention biases of essential and non-essential genes revealed by systematic knockdown analysesen
dc.typeArticle (peer-reviewed)en
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