Extensive Evolutionary Changes in Regulatory Element Activity during Human Origins Are Associated with Altered Gene Expression and Positive Selection 英文参考文献.docVIP

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Extensive Evolutionary Changes in Regulatory Element Activity during Human Origins Are Associated with Altered Gene Expression and Positive Selection 英文参考文献.doc

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Extensive Evolutionary Changes in Regulatory Element Activity during Human Origins Are Associated with Altered Gene Expression and Positive Selection 英文参考文献

ExtensiveEvolutionaryChangesinRegulatoryElement ActivityduringHumanOriginsAreAssociatedwith AlteredGeneExpressionandPositiveSelection YoichiroShibata1.,NathanC.Sheffield1.,OlivierFedrigo1,2,CourtneyC.Babbitt1,2,MatthewWortham1, AlokK.Tewari1,DarinLondon1,LingyunSong1,Bum-KyuLee3,VishwanathR.Iyer3,StephenC.J.Parker4, ElliottH.Margulies4,GregoryA.Wray1,2*,TerrenceS.Furey5,6*,GregoryE.Crawford1,7 * 1InstituteforGenomeSciencesandPolicy,DukeUniversity,Durham,NorthCarolina,UnitedStatesofAmerica,2BiologyDepartment,DukeUniversity,Durham,North Carolina, United States of America, 3Center for Systems and Synthetic Biology, Institute for Cellular and Molecular Biology, Section of Molecular Genetics and Microbiology,UniversityofTexasatAustin,Austin,Texas,UnitedStatesofAmerica,4GenomeTechnologyBranch,NationalHumanGenomeResearchInstitute,National InstitutesofHealth,Bethesda,Maryland,UnitedStatesofAmerica,5DepartmentofGenetics,CarolinaCenterforGenomeSciences,TheUniversityofNorthCarolinaat ChapelHill,ChapelHill,NorthCarolina,UnitedStatesofAmerica,6DepartmentofBiology,CarolinaCenterforGenomeSciences,andLinebergerComprehensiveCancer Center,TheUniversityofNorthCarolinaatChapelHill,ChapelHill,NorthCarolina,UnitedStatesofAmerica,7DepartmentofPediatrics,DivisionofMedicalGenetics,Duke University,Durham,NorthCarolina,UnitedStatesofAmerica Abstract Understandingthemolecularbasisforphenotypicdifferencesbetweenhumansandotherprimatesremainsanoutstanding challenge.Mutationsinnon-codingregulatoryDNAthataltergeneexpressionhavebeenhypothesizedasakeydriverof thesephenotypicdifferences.Thishasbeensupportedbydifferentialgeneexpressionanalysesingeneral,butnotbythe identification of specific regulatory elements responsible for changes in transcription and phenotype. To identify the geneticsourceofregulatorydifferences,wemappedDNaseIhypersensitive(DHS)sites,whichmarkalltypesofactivegene regulatoryelements,genome-wideinthesamecelltypeisolatedfromhuman,chimpanzee,andmacaque.MostDHSsites wereconservedamon