Dosage Sensitivity Shapes the Evolution of Copy-Number Varied Regions 英文参考文献.docVIP

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Dosage Sensitivity Shapes the Evolution of Copy-Number Varied Regions 英文参考文献.doc

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Dosage Sensitivity Shapes the Evolution of Copy-Number Varied Regions 英文参考文献

DosageSensitivityShapestheEvolutionof Copy-NumberVariedRegions BenjaminSchuster-Bo¨ckler1,DonaldConrad2,AlexBateman2* 1European Molecular Biology Laboratory-Centre for Genomic Regulation Systems Biology Unit, Centre for Genomic Regulation, Barcelona, Spain, 2Wellcome Trust SangerInstitute,WellcomeTrustGenomeCampus,Cambridge,UnitedKingdom Abstract Dosage sensitivity is an important evolutionary force which impacts on gene dispensability and duplicability. The newly available data on human copy-number variation (CNV) allow an analysis of the most recent and ongoing evolution. Providedthatheterozygousgenedeletionsandduplicationsactuallychangegenedosage,weexpecttoobservenegative selectionagainstCNVsencompassingdosagesensitivegenes.Inthisstudy,wemakeuseofseveralsourcesofpopulation geneticdatatoidentifyselectiononstructuralvariationsofdosagesensitivegenes.WeshowthatCNVscandirectlyaffect expression levels of contained genes. We find that genes encoding members of protein complexes exhibit limited expression variation and overlap significantly with a manually derived set of dosage sensitive genes. We show that complexesandotherdosagesensitivegenesareunderrepresentedinCNVregions,withaparticularbiasagainstfrequent variations and duplications. These results suggest that dosage sensitivity is a significant force of negative selection on regionsofcopy-numbervariation. Citation: Schuster-Bo¨ckler B, Conrad D, Bateman A (2010) Dosage Sensitivity Shapes the Evolution of Copy-Number Varied Regions. PLoS ONE 5(3): e9474. doi:10.1371/journal.pone.0009474 Editor:JasonE.Stajich,UniversityofCalifornia,Riverside,UnitedStatesofAmerica ReceivedOctober28,2009;AcceptedJanuary12,2010;PublishedMarch10,2010 Copyright:?2010Schuster-Bo¨ckleretal.Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense,whichpermits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding:ThisstudywasfundedbytheWellcomeTrust[grantn