Molecular evolution of DNA-(cytosine-N4) methyltransferases: evidence for their polyphyletic origin

DNA N4-cytosine methyltransferases (N4mC MTases) are a family of S-adenosyl -L-methionine (AdoMet)-dependent MTases, Members of this family were previo usly found to share nine conserved sequence motifs, but the evolutionary ba sis of these similarities has never been studied in detail. We performed ph ylogenetic analysis of 37 known and potential new family members from the m ultiple sequence alignment using distance matrix, parsimony and maximum lik elihood approaches to infer the evolutionary relationship among the N4mC MT ases and classify them into groups of orthologs, Ail the treeing algorithms employed as well as results of exhaustive sequence database searching supp ort a scenario, in which the majority of N4mC MTases, except for M.BalI and M.BamHI, arose by divergence from a common ancestor. Interestingly, MTases M.BalI and M.BamHI apparently originated from NG-adenine MTases and repres ent the most recent addendum to the N4mC MTase family. in addition to the p reviously reported nine sequence motifs, two more conserved sequence patche s were detected. Phylogenetic analysis also provided the evidence for massi ve horizontal transfer of MTase genes, presumably with the whole restrictio n-modification systems, between Bacteria and Archaea.