Dnmt2-dependent methylomes lack defined DNA methylation patterns

Several organismshaveretainedmethyltransferase2(Dnmt2)as their only candidate DNA methyltransferase gene. However, information about Dnmt2-dependent methylation patterns has been limited to a fewisolated loci andtheresults havebeen discussed controversially. Inaddition, recent studieshaveshownthatDnmt2functionsas a tRNA methyltransferase, which raised the possibility that Dnmt2-only genomesmight be unmethylated.Wehave nowusedwhole-genome bisulfitesequencingtoanalyzethemethylomesofDnmt2- onlyorganisms at single-base resolution. Our results show that the genomes of Schistosoma mansoni and Drosophila melanogaster lack detectable DNA methylation patterns. Residual unconverted cytosine residues shared many attributeswith bisulfite deamination artifacts andwere observed at comparable levels in Dnmt2-deficient flies. Furthermore, geneticallymodifiedDnmt2-onlymouse embryonic stem cells lost the DNA methylation patterns found in wild-type cells. Our results thus uncover fundamental differences among animal methylomes and suggest that DNAmethylation is dispensable for a considerable number of eukaryotic organisms.