Formation of Regulatory Modules by Local Sequence Duplication 英文参考文献.docVIP

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Formation of Regulatory Modules by Local Sequence Duplication 英文参考文献.doc

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Formation of Regulatory Modules by Local Sequence Duplication 英文参考文献

FormationofRegulatoryModulesbyLocalSequence Duplication ArmitaNourmohammad,MichaelLa¨ssig* InstituteforTheoreticalPhysics,UniversityofCologne,Ko¨ln,Germany Abstract Turnover of regulatory sequence and function is an important part of molecular evolution. But what are the modes of sequence evolution leading to rapid formation and loss of regulatory sites? Here we show that a large fraction of neighboring transcription factor binding sites in the fly genome have formed from a common sequence origin by local duplications. This modeof evolution is foundtoproduce regulatory information: duplications canseed new sitesin the neighborhoodofexistingsites.Duplicateseedsevolvesubsequentlybypointmutations,oftentowardsbindingadifferent factorthantheirancestralneighborsites.Theseresultsarebasedonastatisticalanalysisof346cis-regulatorymodulesin theDrosophilamelanogastergenome,andacomparisonsetofintergenicregulatorysequenceinSaccharomycescerevisiae. Inflyregulatorymodules,pairsofbindingsitesshowsignificantlyenhancedsequencesimilarityuptodistancesofabout50 bp.Weanalyzethesedataintermsofanevolutionarymodelwithtwodistinctmodesofsiteformation:(i)evolutionfrom independent sequence origin and (ii) divergent evolution following duplication of a common ancestor sequence. Our results suggest that pervasive formation of binding sites by local sequence duplications distinguishes the complex regulatoryarchitectureofhighereukaryotesfromthesimplerarchitectureofunicellularorganisms. Citation:NourmohammadA,La¨ssigM(2011)FormationofRegulatoryModulesbyLocalSequenceDuplication.PLoSComputBiol7(10):e1002167.doi:10.1371/ journal.pcbi.1002167 Editor:AmosTanay,WeizmannInstituteofScience,Israel ReceivedFebruary15,2011;AcceptedJune30,2011;PublishedOctober6,2011 Copyright: ?2011 Nourmohammad,La¨ssig. This isan open-access article distributed under the terms ofthe Creative Commons AttributionLicense, which permitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecr