On the Evolutionary Origin of Eukaryotic DNA Methyltransferases and Dnmt2 英文参考文献.docVIP

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On the Evolutionary Origin of Eukaryotic DNA Methyltransferases and Dnmt2 英文参考文献.doc

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On the Evolutionary Origin of Eukaryotic DNA Methyltransferases and Dnmt2 英文参考文献

OntheEvolutionaryOriginofEukaryoticDNA MethyltransferasesandDnmt2 TomaszP.Jurkowski*,AlbertJeltsch* SchoolofEngineeringandScience,JacobsUniversityBremen,CampusRingBremen,Germany Abstract The Dnmt2 enzymes show strong amino acid sequence similarity with eukaryotic and prokaryotic DNA-(cytosine C5)- methyltransferases.Yet,Dnmt2enzymesfromseveralspecieswereshowntomethylatetRNA-Aspandhadbeenproposed that eukaryotic DNA methyltransferases evolved from a Dnmt2-like tRNA methyltransferase ancestor [Goll et al., 2006, Science, 311, 395-8]. It was the aim of this study to investigate if this hypothesis could be supported by evidence from sequencealignments.Wepresentphylogeneticanalysesbasedonsequencealignmentsofthemethyltransferasecatalytic domainsofmorethan2300eukaryoticandprokaryoticDNA-(cytosineC5)-methyltransferasesandanalyzedthedistribution of DNA methyltransferases in eukaryotic species. The Dnmt2 homologues were reliably identified by an additional conservedCFTmotifnexttomotifIX.AllDNAmethyltransferasesandDnmt2enzymeswereclearlyseparatedfromother RNA-(cytosine-C5)-methyltransferases.Oursequencealignmentsandphylogeneticanalysesindicatethatthelastuniversal eukaryoticancestorcontainedatleastonememberoftheDnmt1,Dnmt2andDnmt3familiesofenzymesandadditional RNAmethyltransferases.ThesimilarityofDnmt2enzymeswithDNAmethyltransferasesandabsenceofsimilaritywithRNA methyltransferasescombinedwiththeirstrongRNAmethylationactivitysuggestthattheancestorofDnmt2wasaDNA methyltransferaseandanearlyDnmt2enzymechangeditssubstratepreferencetotRNA.Thereisnophylogeneticevidence that Dnmt2 was the precursor of eukaryotic Dnmts. Most likely, the eukaryotic Dnmt1 and Dnmt3 families of DNA methyltransferaseshadanindependentoriginintheprokaryoticDNAmethyltransferasesequencespace. Citation: Jurkowski TP, Jeltsch A (2011) On the Evolutionary Origin of Eukaryotic DNA Methyltransferases and Dnmt2. PLoS ONE 6(11): e28104. doi:10.1371/ journal.pone.0028104 Editor:FrankLyko,DeutschesKrebsforschungszentr