Background: Cytosine methylation is a common DNA modification found in most eukaryotic organisms including plants, animals, and fungi. (Cytosine-5)-DNA methyltransferases (C5-DNA MTases) belong to the DNMT family of enzymes that catalyze the transfer of a methyl group from S-adenosyl methionine (SAM) to cytosine residues of DNA. In mammals, four members of the DNMT family have been reported: DNMT1, DNMT3a, DNMT3b and DNMT3L, but only DNMT1, DNMT3a and DNMT3b possess methyltransferase activity. There have been many reports about the methylation landscape in different organisms yet there is no systematic report of how the enzyme DNA (C5) methyltransferases have evolved in different organisms. Result: DNA methyltransferases are found to be present in all three domains of life. However, significant variability has been observed in length, copy number and sequence identity when compared across kingdoms. Sequence conservation is greatly increased in invertebrates and vertebrates compared to other groups. Similarly, sequence length has been found to be increased while domain lengths remain more or less conserved. Vertebrates are also found to be associated with more conserved DNMT domains. Finally, comparison between single nucleotide polymorphisms (SNPs) prevailing in human populations and evolutionary changes in DNMT vertebrate alignment revealed that most of the SNPs were conserved in vertebrates. Conclusion: The sequences (including the catalytic domain and motifs) and structure of the DNMT enzymes have been evolved greatly from bacteria to vertebrates with a steady increase in complexity and specificity. This study provides a systematic report of the evolution of DNA methyltransferase enzyme across different lineages of tree of life. ### Competing Interest Statement The authors have declared no competing interest.
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