GC-Biased Evolution Near Human Accelerated Regions 英文参考文献.docVIP

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GC-Biased Evolution Near Human Accelerated Regions 英文参考文献.doc

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GC-Biased Evolution Near Human Accelerated Regions 英文参考文献

GC-BiasedEvolutionNearHumanAcceleratedRegions SolKatzman1,AndrewD.Kern2,KatherineS.Pollard3,SofieR.Salama1,4,5,DavidHaussler1,4,5 * 1Department of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, California, United States of America, 2Department of Biological Sciences, DartmouthCollege,Hanover,NewHampshire,UnitedStatesofAmerica,3GladstoneInstitutes,UniversityofCaliforniaSanFrancisco,SanFrancisco,California,United States of America, 4Center for Biomolecular Science and Engineering, University of California Santa Cruz, Santa Cruz, California, United States of America, 5Howard HughesMedicalInstitute,UniversityofCaliforniaSantaCruz,SantaCruz,California,UnitedStatesofAmerica Abstract Regionsofthegenomethathavebeenthetargetofpositiveselectionspecificallyalongthehumanlineageareofspecial importanceinhumanbiology.Weusedhighthroughputsequencingcombinedwithmethodstoenrichhumangenomic samplesforparticulartargetstoobtainthesequenceof22chromosomalsamplesathighdepthin40kbneighborhoodsof 49previouslyidentified100–400bpelementsthatshowevidenceforhumanacceleratedevolution.Inadditiontoselection, thepatternofnucleotidesubstitutionsinseveraloftheseelementssuggestedanhistoricalbiasfavoringtheconversionof weak(AorT)allelesintostrong(GorC)alleles.Herewefoundstrongevidenceinthederivedallelefrequencyspectraof many of these 40kb regions for ongoing weak-to-strong fixation bias. Comparison of the nucleotide composition at polymorphiclocitothecompositionatsitesoffixedsubstitutionsadditionallyrevealsthesignatureofhistoricalweak-to- strong fixation bias in a subset of these regions. Most of the regions with evidence for historical bias do not also have signaturesofongoingbias,suggestingthattheevolutionaryforcesgeneratingweak-to-strongbiasarenotconstantover time.Toinvestigatetheroleofselectioninshapingtheseregions,weanalyzedthespatialpatternofpolymorphisminour samples.Wefoundnosignificantevidenceforselectivesweeps,possiblybecausethesignalofsuchsweepshasdecayed beyondthe