Differential Gene Repertoire in Mycobacterium ulcerans Identifies Candidate Genes for Patho-Adaptation 英文参考文献.docVIP

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Differential Gene Repertoire in Mycobacterium ulcerans Identifies Candidate Genes for Patho-Adaptation 英文参考文献.doc

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Differential Gene Repertoire in Mycobacterium ulcerans Identifies Candidate Genes for Patho-Adaptation 英文参考文献

DifferentialGeneRepertoireinMycobacteriumulcerans IdentifiesCandidateGenesforPatho-Adaptation MichaelKa¨ser*,GerdPluschke SwissTropicalInstitute,Basel,Switzerland Abstract Background:Basedonlargegenomicsequencepolymorphisms,severalhaplotypesbelongingtotwomajorlineagesofthe humanpathogenMycobacteriumulceranscouldbedistinguishedamongpatientisolatesfromvariousgeographicorigins. However,thebiologicalrelevanceofinsertional/deletionaldiversityisnotunderstood. Methodology: Using comparative genomics, we have investigated the genes located in regions of difference recently identifiedbyDNAmicroarraybasedhybridisationanalysis.Theanalysedregionsofdifferencecomprise,7%oftheentire M.ulceransgenome. Principal Findings: Several different mechanisms leading to loss of functional genes were identified, ranging from pseudogenization, caused by frame shift mutations or mobile genetic element interspersing, to large sequence polymorphisms.Fourhotspotregionsforgeneticinstabilitywereunveiled.Altogether,229codingsequenceswerefound to be differentially inactivated, constituting a repertoire of coding sequence variation in the rather monomorphic M. ulcerans. Conclusions/Significance:ThedifferentialgeneinactivationpatternsassociatedwiththeM.ulceranshaplotypesidentified candidate genes that may confer enhanced adaptation upon ablation of expression. A number of gene conversions confinedtotheclassicallineagemaycontributetoparticularvirulenceofthisgroupcomprisingisolatesfromAfricaand Australia.Identificationofthisspectrumofanti-virulencegenecandidatesexpandsourunderstandingofthepathogenicity andecologyoftheemerginginfectiousdiseaseBuruliulcer. Citation:Ka¨ser M,PluschkeG(2008)DifferentialGeneRepertoireinMycobacteriumulceransIdentifiesCandidateGenesforPatho-Adaptation.PLoSNeglTrop Dis2(12):e353.doi:10.1371/journal.pntd.0000353 Editor:PamelaL.C.Small,UniversityofTennessee,UnitedStatesofAmerica ReceivedAugust4,2008;AcceptedDecember2,2008;PublishedDecember23,2008 Copyright: ? 2008 Ka¨ser, Plusc