Evolution of DNMT2 in drosophilids: Evidence for positive and purifying selection and insights into new protein (pathways) interactions

• Published in: Genetics and molecular biology Vol. 41; no. 1 suppl 1; pp. 215 - 234
• Main Authors: Vieira, Gilberto Cavalheiro, D'Ávila, Marícia Fantinel, Zanini, Rebeca, Deprá, Maríndia, da Silva Valente, Vera Lúcia
• Format: Journal Article
• Language: English
• Published: Brazil Sociedade Brasileira de Genetica 01.01.2018; Sociedade Brasileira de Genética
• Subjects: BIOCHEMISTRY & MOLECULAR BIOLOGY; Biological evolution; Deoxyribonucleic acid; DNA; DNA methylation; DNA methyltransferase; Dnmt2; Drosophila; Drosophilidae; epigenetic; GENETICS & HEREDITY; Homology; Insects; Molecular evolution; Phylogeny; Physicochemical properties; Positive selection; positive-destabilizing selection; Proteins; Structure-function relationships; Substrate specificity; Substrates; Dnmt2; positive-destabilizing selection; positive selection; epigenetic; Drosophila
• ISSN: 1415-4757; 1678-4685; 1678-4685
• DOI: 10.1590/1678-4685-GMB-2017-0056

The DNA methyltransferase 2 (DNMT2) protein is the most conserved member of the DNA methyltransferase family. Nevertheless, its substrate specificity is still controversial and elusive. The genomic role and determinants of DNA methylation are poorly understood in invertebrates, and several mechanisms and associations are suggested. In Drosophila, the only known DNMT gene is Dnmt2. Here we present our findings from a wide search for Dnmt2 homologs in 68 species of Drosophilidae. We investigated its molecular evolution, and in our phylogenetic analyses the main clades of Drosophilidae species were recovered. We tested whether the Dnmt2 has evolved neutrally or under positive selection along the subgenera Drosophila and Sophophora and investigated positive selection in relation to several physicochemical properties. Despite of a major selective constraint on Dnmt2, we detected six sites under positive selection. Regarding the DNMT2 protein, 12 sites under positive-destabilizing selection were found, which suggests a selection that favors structural and functional shifts in the protein. The search for new potential protein partners with DNMT2 revealed 15 proteins with high evolutionary rate covariation (ERC), indicating a plurality of DNMT2 functions in different pathways. These events might represent signs of molecular adaptation, with molecular peculiarities arising from the diversity of evolutionary histories experienced by drosophilids.