A Genetic Code Alteration Is a Phenotype Diversity Generator in the Human Pathogen Candida albicans 英文参考文献.docVIP

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A Genetic Code Alteration Is a Phenotype Diversity Generator in the Human Pathogen Candida albicans 英文参考文献.doc

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A Genetic Code Alteration Is a Phenotype Diversity Generator in the Human Pathogen Candida albicans 英文参考文献

AGeneticCodeAlterationIsaPhenotypeDiversity GeneratorintheHumanPathogenCandidaalbicans IsabelMiranda,RitaRocha,MariaC.Santos,DenisaD.Mateus,GabrielaR.Moura,LauraCarreto,ManuelA.S.Santos* DepartmentofBiology,CentrodeEstudosdoAmbienteedoMar(CESAM),UniversityofAveiro,Aveiro,Portugal Background. The discovery of genetic code alterations and expansions in both prokaryotes and eukaryotes abolished the hypothesisofafrozenanduniversalgeneticcodeandexposedunanticipatedflexibilityincodonandaminoacidassignments. Itisnowclearthatcodonidentityalterationsinvolvesenseandnon-sensecodonsandcanoccurinorganismswithcomplex genomes and proteomes. However, the biological functions, the molecular mechanisms of evolution and the diversity of geneticcodealterationsremainlargelyunknown.InvariousspeciesofthegenusCandida,theleucineCUGcodonisdecoded asserinebyauniqueserinetRNAthatcontainsaleucine59-CAG-39anticodon(tRNACAGSer).Weareusingthiscodonidentity redefinitionasamodelsystemtoelucidatetheevolutionofgeneticcodealterations.Methodology/PrincipalFindings.We havereconstructedtheearlystagesoftheCandidageneticcodealterationbyengineeringtRNAsthatpartiallyrevertedthe identityofserineCUGcodonsbacktotheirstandardleucinemeaning.Suchgeneticcodemanipulationhadprofoundcellular consequencesasitexposedimportantmorphologicalvariation,alteredgeneexpression,re-arrangedthekaryotype,increased cell-celladhesionandsecretionofhydrolyticenzymes.Conclusion/Significance.Ourstudyprovidesthefirstexperimental evidenceforanimportantroleofgeneticcodealterationsasgeneratorsofphenotypicdiversityofhighselectivepotentialand supportsthehypothesisthattheyspeedupevolutionofnewphenotypes. Citation: MirandaI,RochaR,SantosMC,MateusDD,MouraGR,etal(2007)AGeneticCodeAlterationIsaPhenotypeDiversityGeneratorinthe HumanPathogenCandidaalbicans.PLoSONE2(10):e996.doi:10.1371/journal.pone.0000996 INTRODUCTION identity of UAA and UAG stop codons to glutamine in various ciliatesinvolvedfirstbasemisreadingbyglutaminetRNAs,which decode glutami