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

Abstract

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.

Adaptive evolution in DNMT2 supports its role in the dipteran immune response

“…These findings suggest several instances of recent adaptive evolution within Drosophila DNMT2 since its divergence from Culicidae. Notably, these results are in line with the findings reported by Vieira et.al (Vieira, et al 2018).…”

“…As many dipterans are vectors for human pathogens, and infected by the endosymbiont Wolbachia, we hypothesized that DNMT2 in this group of insects may show evidence of positive selection. Indeed, evidence of positive selection in Drosophila DNMT2 has been reported earlier by Vieira et.al (Vieira, et al 2018). However, that study was limited to identifying signatures of positive selection within Drosophila species.…”

Characterizing the transcriptional expression and in situ localization of the Dnmt2 gene in Drosophila willistoni

“…However, what is observed in terms of recombination in the telomeric regions of Drosophila melanogaster is that there is a great suppression of crossing over events, within and in regions proximal to the telomeres [60]. These aspects are in agreement with previous findings of our research group, in which D. willistoni Dnmt2 shows the highest rate of nucleotide substitution per codon in relation to the other drosophilids and different selective pressures 14 at specific sites involved in an interaction-driven co-evolution with other genes [61]. In the present work, we verified that the expression of Dnmt2 in D. willistoni is closely related to its ontogenetic stages.…”

“…We also conduct the in situ localization of the Dnmt2 gene, revealing its presence in the arm IIL (Muller B element). The Dnmt2 is located in the subtelomeric region, and this brings up a series of issues that involve the peculiar characteristics of D. willistoni Dnmt2 enzyme, like evolutionary pattern in nucleotide substitutions rates [61], the high prevalence of basic amino acids residues in its target recognition domain surface [62] and the epigenetic phenomena of sex-specific methylation [15,25]. Detection of Dnmt2 by conventional RT-PCR.…”

Queen pheromone modulates the expression of epigenetic modifier genes in the brain of honeybee workers

“…2016). DNMT2 is present in insects that have lost several or all of the other DNMTs, as is the case in drosophilids (Vieira et al . 2018).…”