Population Genomic Scan for Candidate Signatures of Balancing Selection to Guide Antigen Characterization in Malaria Parasites 英文参考文献.docVIP
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Population Genomic Scan for Candidate Signatures of Balancing Selection to Guide Antigen Characterization in Malaria Parasites 英文参考文献
PopulationGenomicScanforCandidateSignaturesof
BalancingSelectiontoGuideAntigenCharacterizationin
MalariaParasites
AlfredAmambua-Ngwa1,KevinK.A.Tetteh2,MagnusManske3,NataliaGomez-Escobar1,
LindsayB.Stewart2,M.ElizabethDeerhake2,IanH.Cheeseman1,2,ChristopherI.Newbold4,
AnthonyA.Holder5,EllenKnuepfer5,OmarJanha1,MuminatouJallow1,SusanaCampino3,
BronwynMacInnis3,DominicP.Kwiatkowski3,6,DavidJ.Conway1,2
*
1MedicalResearchCouncilUnit,Fajara,Banjul,TheGambia,2DepartmentofPathogenMolecularBiology,LondonSchoolofHygieneandTropicalMedicine,London,
UnitedKingdom,3WellcomeTrustSangerInstitute,Hinxton,UnitedKingdom,4WeatherallInstituteofMolecularMedicine,UniversityofOxford,Oxford,UnitedKingdom,
5Division of Parasitology,MRC National Institute for Medical Research,London, United Kingdom, 6Wellcome Trust Centrefor Human Genetics, University of Oxford,
Oxford,UnitedKingdom
Abstract
Acquired immunity in vertebrates maintains polymorphisms in endemic pathogens, leading to identifiable signatures of
balancingselection.TocomprehensivelysurveyforgenesundersuchselectioninthehumanmalariaparasitePlasmodium
falciparum, we generated paired-end short-read sequences of parasites in clinical isolates from an endemic Gambian
population,whichweremappedtothe3D7strainreferencegenometoyieldhigh-qualitygenome-widecodingsequence
datafor65isolates.Aminorityofgenesdidnotmapreliably,includingthehypervariablevar,rifin,andstevorfamilies,but
5,056 genes (90.9% of all in the genome) had .70% sequence coverage with minimum read depth of 5 for at least 50
isolates,ofwhich2,853genescontained3ormoresinglenucleotidepolymorphisms(SNPs)foranalysisofpolymorphicsite
frequencyspectra.Againstanoverallbackgroundofnegativelyskewedfrequencies,asexpectedfromhistoricalpopulation
expansion combined with purifying selection, the outlying minority of genes with signatures indicating exceptionally
intermediate frequencies were identified. Comparing genes with different stage-specificity, such signatures were most
commoninthose
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