Evolution of cagA Oncogene of Helicobacter pylori through Recombination 英文参考文献.docVIP

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Evolution of cagA Oncogene of Helicobacter pylori through Recombination 英文参考文献.doc

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Evolution of cagA Oncogene of Helicobacter pylori through Recombination 英文参考文献

EvolutionofcagAOncogeneofHelicobacterpylori throughRecombination YoshikazuFuruta1,2,KojiYahara3,4,MasanoriHatakeyama5,IchizoKobayashi1,2,6* 1DepartmentofMedicalGenomeSciences,GraduateSchoolofFrontierSciences,UniversityofTokyo,Minato-ku,Tokyo,Japan,2InstituteofMedicalScience,University ofTokyo,Minato-ku,Tokyo,Japan,3GraduateSchoolofMedicine,KurumeUniversity,Kurume,Fukuoka,Japan,4FujitsuKyushuSystemsLTD,Fukuoka,Fukuoka,Japan, 5Department of Microbiology, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan, 6Department of Biophysics and Biochemistry, Graduate SchoolofScience,UniversityofTokyo,Minato-ku,Tokyo,Japan Abstract Helicobacterpyloriisagastricpathogenthatinfectshalfthehumanpopulationandcausesgastritis,ulcers,andcancer.The cagAgeneproductisamajorvirulencefactorassociatedwithgastriccancer.Itisinjectedintoepithelialcells,undergoes phosphorylationbyhostcellkinases,andperturbshostsignalingpathways.CagAisknownforitsgeographical,structural, andfunctionaldiversityintheC-terminalhalf,whereanEPIYAhost-interactingmotifisrepeated.TheWesternversionof CagAcarriestheEPIYAsegmenttypesA,B,andC,whiletheEastAsianCagAcarriestypesA,B,andDandshowshigher virulence.Manystructuralvariantssuchasduplicationsanddeletionsarereported.Inthisstudy,wegainedinsightintothe relationshipsofCagAvariantsthroughvariousmodesofrecombination,byanalyzingallknowncagAvariantsattheDNA sequencelevelwiththesinglenucleotideresolution.Processesthatoccurredwere:(i)homologousrecombinationbetween DNAsequencesforCagAmultimerization(CM)sequence;(ii)recombinationbetweenDNAsequencesfortheEPIYAmotif; and(iii)recombinationbetweenshortsimilarDNAsequences.ThelefthalfoftheEPIYA-DsegmentcharacteristicofEast AsianCagAwasderivedfromWesterntypeEPIYA,withAmerindtypeEPIYAastheintermediate,throughrearrangementsof specificsequenceswithinthegene.Adaptiveaminoacidchangesweredetectedinthevariableregionaswellasinthe conserved region at sites to which no specific function has yet been assigned. Each showed a uni