Selective Constraint on Noncoding Regions of Hominid Genomes 英文参考文献.docVIP

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Selective Constraint on Noncoding Regions of Hominid Genomes 英文参考文献.doc

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Selective Constraint on Noncoding Regions of Hominid Genomes 英文参考文献

SelectiveConstraintonNoncodingRegions ofHominidGenomes Eliot C.Bush, Bruce T.Lahn* HowardHughesMedicalInstitute,DepartmentofHumanGenetics,UniversityofChicago,Chicago,Illinois,UnitedStatesofAmerica An important challenge for human evolutionary biology is to understand the genetic basis of human–chimpanzee differences.Oneinfluentialideaholdsthatsuchdifferencesdepend,toalargeextent,onadaptivechangesingene expression. An important step in assessing this hypothesis involves gaining a better understanding of selective constraint on noncoding regions of hominid genomes. In noncoding sequence, functional elements are frequently smallandcanbeseparatedbylargenonfunctionalregions.Forthisreason,constraintinhominidgenomesislikelyto bepatchy.Hereweuseconservationinmoredistantlyrelatedmammalsandamniotesasawayofidentifyingsmall sequencewindowsthatarelikelytobefunctional.Wefindthatputativelyfunctionalnoncodingelementsdefinedin thismanneraresubjecttosignificantselectiveconstraintinhominids. Citation:BushEC,LahnBT(2005)Selectiveconstraintonnoncodingregionsofhominidgenomes.PLoSComputBiol1(7):e73. Introduction Results/Discussion Thirtyyearsago,KingandWilson[1]raisedakeyquestion in human evolutionary genetics: Given that humans and chimpanzees have extremely similar genomes, what can accountforthelargebiologicaldifferencesbetweenthetwo species? They proposed the provocative hypothesis that changes in the regulation of gene expression have played a centralroleinde?ningthesedifferences. Since then, some progress has been made toward under- standingthegeneticbasisofhuman–chimpanzeedifferences. Moststudies havefocusedon proteincodingregions [2–10]. In comparison, much less progress has been made toward understanding the functional signi?cance of noncoding sequenceevolution,andasaresult,ithasbeenhardtoassess KingandWilson’shypothesis. An important step in assessing that hypothesis is to examine the level of selective constraint in hominid non- codingregions.Theapproachtakeninarecentst