DNA Methylation in Honey Bees and the Unresolved Questions in Insect Methylomics

DNA methylation has been found in most invertebrate lineages except for Diptera, Placozoa and the majority of Nematoda. In contrast to the mammalian methylation toolkit that consists of one DNMT1 and several DNMT3s, some of which are catalytically inactive accessory isoforms, invertebrates have different combinations of these proteins with some using just one DNMT1 and the others, like the honey bee, two DNMT1s one DNMT3. Although the insect DNMTs show sequence similarity to mammalian DNMTs, their in vitro and in vivo properties are not well investigated. In contrast to heavily methylated mammalian genomes, invertebrate genomes are only sparsely methylated in a 'mosaic' fashion with the majority of methylated CpG dinucleotides found across gene bodies that are frequently associated with active transcription. Additional work also highlights that obligatory methylated epialleles influence transcriptional changes in a context-specific manner. We argue that some of the lineage-specific properties of DNA methylation are the key to understanding the role of this genomic modification in insects. Future mechanistic work is needed to explain the relationship between insect DNMTs, genetic variation, differential DNA methylation, other epigenetic modifications, and the transcriptome in order to fully understand the role of DNA methylation in converting genomic sequences into phenotypes.