Alignment of vertebrate and invertebrate DNA methyltransferases; 2 (Dnmt2) evidenced an over-all evolutionary conservation of these proteins. However, alignment revealed a vertebrate-specific stretch of about forty amino acids located between the catalytic motif VIII and the target recognition domain that is constantly absent from insect homologues. The analysis of the three-dimensional structure of DNA methyltransferase indicated that this vertebrate specific Dnmt2 portion is located at the DNA binding domain whose structure is essential for the discrimination of the proper target sequence. Insect Dnmt2 enzymes are, therefore, devoid of a portion of the DNA binding domain suggesting that this structural change may alter the methylation target of insect Dnmt2 Making cytosine methylation not limited to the vertebrate canonical CpG but extended to cytosine residues belonging to other dinucleotides.