Gene-Specific Signatures of Elevated Non-Synonymous Substitution Rates Correlate Poorly across the Plasmodium Genus 英文参考文献.docVIP

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Gene-Specific Signatures of Elevated Non-Synonymous Substitution Rates Correlate Poorly across the Plasmodium Genus 英文参考文献.doc

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Gene-Specific Signatures of Elevated Non-Synonymous Substitution Rates Correlate Poorly across the Plasmodium Genus 英文参考文献

Gene-SpecificSignaturesofElevatedNon-Synonymous SubstitutionRatesCorrelatePoorlyacrossthe PlasmodiumGenus GarethD.Weedall1*,SpencerD.Polley1,DavidJ.Conway1,2 1DepartmentofInfectiousandTropicalDiseases,LondonSchoolofHygieneandTropicalMedicine,London,UnitedKingdom,2MedicalResearchCouncilLaboratories, Fajara,Banjul,TheGambia Abstract Background:Comparativegenomeanalysesofparasitesallowlargescaleinvestigationofselectivepressuresshapingtheir evolution. An acute limitation to such analysis of Plasmodium falciparum is that there is only very partial low-coverage genome sequence of the most closely related species, the chimpanzee parasite P. reichenowi. However, if orthologous genes have been under similar selective pressures throughout the Plasmodium genus then positive selection on the P. falciparumlineagemightbepredictedtosomeextentbyanalysisofotherlineages. PrincipalFindings:Here,threeindependentpairsofcloselyrelatedspeciesindifferentsub-genericclades(P.falciparum andP.reichenowi;P.vivaxandP.knowlesi;P.yoeliiandP.berghei)werecomparedforasetof43candidateligandgenes consideredlikelytobeunderpositivedirectionalselectionandasetof102controlgenesforwhichtherewasnoselective hypothesis.Theratiosofnon-synonymoustosynonymoussubstitutions(dN/dS)weresignificantlyelevatedinthecandidate ligandgenescomparedtocontrolgenesineachofthethreeclades.However,therankordercorrelationofdN/dSratiosfor individualcandidategeneswasverylow,lessthanthecorrelationforthecontrolgenes. Significance:TheinabilitytopredictpositiveselectiononageneinonelineagebyidentifyingelevateddN/dSratiosinthe orthologuewithinanotherlineageneedstobenoted,asitreflectsthatadaptivemutationsaregenerallyrareeventsthat lead to fixation in individual lineages. Thus it is essential to complete the genome sequences of particular species of phylogeneticimportance,suchasP.reichenowi. Citation: Weedall GD, Polley SD, Conway DJ (2008) Gene-Specific Signatures of Elevated Non-Synonymous Substitution Rates Correlate Poorly across the P