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1、8EvolutionofSirtuinsFromArchaeatoVertebratesRoyA.Frye,MD,PhDCONTENTSSUMMARYINTRODUCTIONSIRTUINSEQUENCESURVEYANDALIGNMENTMETHODSSIRT1ORTHOLOGSSIRT2ORTHOLOGSSIRT3ORTHOLOGSSIRT4ORTHOLOGSSIRT5ORTHOLOGSSIRT6ORTHOLOGSSIRT7ORTHOLOGSCONCLUSIONSREFERENCESSUMMARYMosteukaryoticsirtuins(sir2-lik
2、eproteins)canbegroupedintofourclasses.Indeuterostomessuchasvertebrates,theurochordateseasquirtCiona,andtheechinodermseaurchinStrongylocentrotus,therearesevensirtuins.ClassIincludesSIRT1,SIRT2,andSIRT3.SIRT4isinclassIIandSIRT5isinclassIII.ClassIVincludesSIRT6andSIRT7.FishhavetwoSIRT5o
3、rthologswhilemostothervertebrateshaveonlyoneversionofeachofthesevensirtuins.ArthropodslackSIRT3,andsomearthropods(e.g.,Drosophila)lackSIRT5,butotherarthropodshaveSIRT1,SIRT2,From:CancerDrugDiscoveryandDevelopmentHistoneDeacetylases:TranscriptionalRegulationandOtherCellularFunctionsEd
4、itedby:E.Verdin©HumanaPressInc.,Totowa,NJ183184FryeSIRT4,SIRT5,SIRT6,andSIRT7.Mostprokaryoticsirtuinscanbegroupedintothreecategories:thesameclassIIandclassIIIcategoriesasseenineukaryotes,andaclassU,whichcouldbetheprecursoroftheeukaryoticclassIandclassIVsirtuins.Amodelisproposedinwhic
5、hthefirsteukaryote(whichresultedfromtheengulfmentofanα-proteobacteriumbyanarchaean)receivedaclassIIIsirtuinfromthearchaeanparent,whiletheclassIIsirtuinandaclassUsirtuincamefromtheα-proteobacteriumparent.WhilemosteukaryoticclassIIIsirtuinsappeartobederivedfromanarchaealclassIIIsirtuin
6、,theKinetoplastida(LeishmaniaandTrypanosoma)haveaclassIIIsirtuingenethatappearstobeofγ-proteobacterialorigin,possiblyanexampleoflateralgenetransfer.Thesevenmammaliansirtuinsarealignedandcontrastedwithsirtuinsfromdiverseeukaryoticandprokaryoticorganisms.KeyWords:sir2,sirtuin,evolution
7、,homology,phylogeny,SIRT1,SIRT2,SIRT3,SIRT4,SIRT5,SIRT6,SIRT7.INTRODUCTIONThesirtuinsareafamilyofregulatoryproteinsthatareofancientevolutionaryoriginsincetheyarefoundinmostprokaryotesandinalleukaryotes(1,2).SirtuinsareNAD-dependentacetyllysinedeacetylases;theprototypeofthesirtuinsist
8、heSaccharomy
