Repair-Mediated Duplication by Capture of Proximal Chromosomal DNA Has Shaped Vertebrate Genome Evolution 英文参考文献.docVIP

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Repair-Mediated Duplication by Capture of Proximal Chromosomal DNA Has Shaped Vertebrate Genome Evolution 英文参考文献.doc

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Repair-Mediated Duplication by Capture of Proximal Chromosomal DNA Has Shaped Vertebrate Genome Evolution 英文参考文献

Repair-MediatedDuplicationbyCaptureofProximal ChromosomalDNAHasShapedVertebrateGenome Evolution JohnK.PaceII1¤,ShurjoK.Sen2,MarkA.Batzer2,Ce′dricFeschotte1* 1Department ofBiology, University ofTexas atArlington, Arlington, Texas, United States ofAmerica, 2Department ofBiological Sciences, Louisiana State University, BatonRouge,Louisiana,UnitedStatesofAmerica Abstract DNA double-strand breaks (DSBs) are a common form of cellular damage that can lead to cell death if not repaired promptly. Experimental systems have shown that DSB repair in eukaryotic cells is often imperfect and may result in the insertionofextrachromosomalDNAortheduplicationofexistingDNAatthebreakpoint.Theseeventsarethoughttobea sourceofgenomicinstabilityandhumandiseases,butitisunclearwhethertheyhavecontributedsignificantlytogenome evolution. Here we developed an innovative computational pipeline that takes advantage of the repetitive structure of genomestodetectrepair-mediatedduplicationevents(RDs)thatoccurredinthegermlineandcreatedinsertionsofatleast 50bpofgenomicDNA.Usingthispipelineweidentifiedover1,000probableRDsinthehumangenome.Ofthese,824were intra-chromosomal,closelylinkedduplicationsofupto619bpbearingthehallmarksofthesynthesis-dependentstrand- annealingrepairpathway.Thismechanismhasduplicatedhundredsofsequencespredictedtobefunctionalinthehuman genome,includingexons,UTRs,intronsplicesitesandtranscriptionfactorbindingsites.Datingoftheduplicationevents usingcomparativegenomicsandexperimentalvalidationrevealedthatthemechanismhasoperatedcontinuouslybutwith decreasing intensity throughout primate evolution. The mechanism has produced species-specific duplications in all primate species surveyed and is contributing to genomicvariation among humans.Finally, weshow that RDs havealso occurred,albeitatalowerfrequency,innon-primatemammalsandothervertebrates,indicatingthatthismechanismhas beenanimportantforceshapingvertebrategenomeevolution. Citation: Pace JK II, Sen SK, Batzer MA, Feschotte C (2009) R