Evolution of the Multi-Domain Structures of Virulence Genes in the Human Malaria Parasite, Plasmodium falciparum 英文参考文献.docVIP

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Evolution of the Multi-Domain Structures of Virulence Genes in the Human Malaria Parasite, Plasmodium falciparum 英文参考文献.doc

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Evolution of the Multi-Domain Structures of Virulence Genes in the Human Malaria Parasite, Plasmodium falciparum 英文参考文献

EvolutionoftheMulti-DomainStructuresofVirulence GenesintheHumanMalariaParasite,Plasmodium falciparum CarolineO.Buckee1,MarioRecker2* 1Center for Communicable Disease Dynamics, Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America, 2DepartmentofZoology,UniversityofOxford,Oxford,UnitedKingdom Abstract ThevargenefamilyofPlasmodiumfalciparumencodestheimmunodominantvariantsurfaceantigensPfEMP1.Thesehighly polymorphic proteins are important virulence factors that mediate cytoadhesion to a variety of host tissues, causing sequestrationofparasitizedredbloodcellsinvitalorgans,includingthebrainorplacenta.Acquisitionofvariant-specific antibodiescorrelateswithprotectionagainstseveremalarialinfections;however,understandingtherelationshipbetween gene expression and infection outcome is complicated by the modular genetic architectures of var genes that encode varyingnumbersofantigenicdomainswithdifferentialbindingspecificities.Byanalyzingthedomainarchitecturesoffully sequenced var gene repertoires we reveal a significant, non-random association between the number of domains comprisingavargeneandtheirsequenceconservation.Assuch,vargenescanbegroupedintothosethatareshortand diverseandgenesthatarelongandconserved,suggestinggenelengthasanimportantcharacteristicintheclassificationof vargenes.Wethenuseanevolutionaryframeworktodemonstratehowthesameevolutionaryforcesactingonthelevelof an individual gene may have also shaped the parasite’s gene repertoire. The observed associations between sequence conservation,genearchitectureandrepertoirestructurecanthusbeexplainedbyatrade-offbetweenoptimizingwithin- host fitnessandminimizing between-hostimmuneselectionpressure. Ourresults demonstratehowsimple evolutionary mechanisms can explain var gene structuring on multiple levels and have important implications for understanding the multifacetedepidemiologyofP.falciparummalaria. Citation:BuckeeCO,ReckerM(2012)EvolutionoftheMulti-DomainStruct