Prospective Identification of Malaria Parasite Genes under Balancing Selection 英文参考文献.docVIP

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Prospective Identification of Malaria Parasite Genes under Balancing Selection 英文参考文献.doc

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Prospective Identification of Malaria Parasite Genes under Balancing Selection 英文参考文献

ProspectiveIdentificationofMalariaParasiteGenes underBalancingSelection KevinK.A.Tetteh1,LindsayB.Stewart1,LynetteIsabellaOchola1,2,3,AlfredAmambua-Ngwa2, AlanW.Thomas4,KevinMarsh3,GarethD.Weedall1,5,DavidJ.Conway1,2 * 1DepartmentofInfectiousandTropicalDiseases,LondonSchoolofHygieneandTropicalMedicine,London,UnitedKingdom,2MRCLaboratories,Fajara,Banjul,The Gambia,3KEMRICentreforGeographicMedicineResearch,Coast,Kilifi,Kenya,4BiomedicalPrimateResearchCentre,Rijswijk,TheNetherlands,5SchoolofBiological Sciences,UniversityofLiverpool,Liverpool,UnitedKingdom Abstract Background:Endemichumanpathogensaresubjecttostrongimmuneselection,andinterrogationofpathogengenome variationforsignaturesofbalancingselectioncanidentifyimportanttargetantigens.Severalmajorantigengenesinthe malaria parasite Plasmodium falciparum have shown such signatures in polymorphism-versus-divergence indices (comparingwiththechimpanzeeparasiteP.reichenowi),andinallelefrequencybasedindices. Methodology/PrincipalFindings:Tocomparemethodsforprospectiveidentificationofgenesunderbalancingselection, 26additionalgenesknownorpredictedtoencodesurface-exposedproteinsoftheinvasivebloodstagemerozoitewere first sequenced from a panel of 14 independent P. falciparum cultured lines and P. reichenowi. Six genes at the positive extremesofoneorbothoftheHudson-Kreitman-Aguade(HKA)andMcDonald-Kreitman(MK)indiceswereidentified.Allele frequencybasedanalysiswasthenperformedonaGambianP.falciparumpopulationsampleforthesesixgenesandthree othersascontrols.Tajima’sD(TjD)indexwasmosthighlypositiveforthemsp3/6-likePF10_0348(TjD=1.96)aswellasthe positivecontrolama1antigengene(TjD=1.22).AcrossthegenestherewasastrongcorrelationbetweenpopulationTjD valuesandtherelativeHKAindices(whetherderivedfromthepopulationorthepanelofculturedlaboratoryisolates),but nocorrelationwiththeMKindices. Conclusions/Significance:Althoughfewindividualparasitegenesshowsignificantevidenceofbalancingselection,analysis ofpopulationgenomicandcomparativesequenced