DNA Methylation and Gene Regulation in Honeybees: From Genome-Wide Analyses to Obligatory Epialleles

Abstract

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. Importantly, this gene body methylation is frequently associated with active transcription, and studies in the honeybee have shown that there are strong links between gene body methylation and alternative splicing. Additional work also highlights that obligatory methylated epialleles influence transcriptional changes in a context-specific manner. Here we discuss the current knowledge in this emerging field and highlight both similarities and differences between DNA methylation systems in mammals and invertebrates. Finally, we argue that the relationship between genetic variation, differential DNA methylation, other epigenetic modifications and the transcriptome must be further explored to fully understand the role of DNA methylation in converting genomic sequences into phenotypes.

Genetics and Evolution of Social Behavior in Insects

“…The second factor that should always be controlled is the genetic background because it could independently affect phenotypic traits and molecular mechanisms. Genetic effects on caste determination and worker behavior are common (84,140), and DNA methylation patterns have been found to be associated with the genetic background in bees (165). Additional factors that should be controlled because they affect gene expression include the social environment (89,92,96), temperature (79), and nutrition (171).…”

Beyond Royalactin and a master inducer explanation of phenotypic plasticity in honey bees

“…Given the complex nature of this diet and the need for copious amounts of royal jelly over a period of 6 days to produce a mature queen, a conventional explanation of this phenomenon is that a finely tuned feeding regime leads to changes in metabolic flux 26,27 , hormone levels 36–38 and activation of a cascade of epigenetic regulatory mechanisms including DNA methylation, histone modifications and non-protein coding RNAs, which have the capacity to alter global gene regulation required for producing contrasting organismal outcomes from one genome 7,25–27,39 . Because enzymes responsible for adding or removing epigenetic marks are dependent upon, or influenced by, metabolites, metabolic flux is now recognised as an important driver of DNA and histone modifications and thus a prime mover in gene regulation 24,25,40 (Fig. 1).…”

“…As shown in Fig. 3, the choice of the two alternate developmental trajectories can be imagined as a growing honey bee female larva (depicted as a yellow ball) travelling across a landscape of mountains and valleys where the valleys represent ‘attractor states or basins’ 24,80 . In this illusory landscape, a developing organism travels along an irregular terrain of phenotypic attractors following a set of instructional vectors until it reaches its final state that is said to be optimal under a given set of conditions 79 .…”

“…It is a striking example of regulatory processes utilising nutritional impact on developmental reprogramming of multipotent cells and how a specialised diet interacting with a single genotype, mediated by epigenomic changes can generate two contrasting organisms 7,21,22 . Currently, this is the most experimentally accessible model in which a defined environmental stimulus, royal jelly, controls post-embryonic development by means of gene regulation via epigenomic modifiers 7,21,23,24 . This highly successful evolutionary invention has been the topic of numerous studies including micro-array and ultra-deep RNA sequencing often combined with genomics and methylomics (epigenomics) that provided initial impetus to unravelling the intricate genetic network driving mechanistic features of phenotypic plasticity in honey bees 25–27 .…”

Developmental and loco-like effects of a swainsonine-induced inhibition ofα-mannosidase in the honey bee,Apis mellifera

“…Yet, individuals carrying such alleles exist in human and other populations (Eyre-Walker & Keightley, 2007; Eyre-Walker, Woolfit & Phelps, 2006; Kondrashov, 1995; Trask et al, 2016) posing a question what keeps natural selection from getting rid of them? Recently, we have uncovered several differentially methylated obligatory epialleles of the gene coding for lysosomal α-mannosidase (AmLAM, GB44223) in the honey bee population (Wedd, Kucharski & Maleszka, 2016; Wedd & Maleszka, 2016). These epialleles correlate with context-dependent changes to AmLAM gene expression, with certain epialleles found to be associated with a lower expression of AmLAM.…”