Intergenerational transfer of DNA methylation marks in the honey bee

Abstract

The evolutionary significance of epigenetic inheritance is controversial. While epigenetic marks such as DNA methylation can affect gene function and change in response to environmental conditions, their role as carriers of heritable information is often considered anecdotal. Indeed, near-complete DNA methylation reprogramming, as occurs during mammalian embryogenesis, is a major hindrance for the transmission of nongenetic information between generations. Yet it remains unclear how general DNA methylation reprogramming is across the tree of life. Here we investigate the existence of epigenetic inheritance in the honey bee. We studied whether fathers can transfer epigenetic information to their daughters through DNA methylation. We performed instrumental inseminations of queens, each with four different males, retaining half of each male’s semen for whole genome bisulfite sequencing. We then compared the methylation profile of each father’s somatic tissue and semen with the methylation profile of his daughters. We found that DNA methylation patterns were highly conserved between tissues and generations. There was a much greater similarity of methylomes within patrilines (i.e., father-daughter subfamilies) than between patrilines in each colony. Indeed, the samples’ methylomes consistently clustered by patriline within colony. Samples from the same patriline had twice as many shared methylated sites and four times fewer differentially methylated regions compared to samples from different patrilines. Our findings indicate that there is no DNA methylation reprogramming in bees and, consequently, that DNA methylation marks are stably transferred between generations. This points to a greater evolutionary potential of the epigenome in invertebrates than there is in mammals.

DNA methylation is not a driver of gene expression reprogramming in young honey bee workers

“…This may reflect the small number of maternal and paternal epialleles predicted for polyandrous insects (59). Interestingly, the colony-specific methylation patterns are inherited from drones to their worker daughters (40), suggesting a role for the paternally inherited epialleles to the composition of colony-specific worker methylomes.…”

“…The finding that the knockdown of the Dnmt3 gene function, a key orchestrator of honey bee development, is lethal at early development (16) suggests that DNA methylation is essential to honey bee viability. Furthermore, the colony-specific methylation patterns are, at least in part, sequence-specific (32,39,40). Ultra-deep amplicon sequencing analyses identified that a honey bee brain displays only a small repertoire of methylation patterns.…”

“…More recent studies, however, now cast doubt on the role of gene body DNA methylation as a flexible regulator of gene expression in social insects, and an emerging consensus is that DNA methylation is genotype-specific (30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41). For example, a reanalysis of the Dnmt3 knockdown data of Li-Byarlay et al (2013) suggested that the original analysis had overestimated the number of regulated genes, and that the Dnmt3 knockdown had in fact only a minor effect on the honey bee gene body methylation pattern, and hence, on gene expression (37).…”

Evolved changes in DNA methylation in response to the sustained loss of parental care in the burying beetle

“…Another explanation is that population differences in DNA methylation could have arisen randomly ( i.e ., epimutations) and then been selected by the environment. This could be made more possible in insects by the reported high heritability of arthropod gene body methylation (Liew et al, 2020; Yagound et al, 2020). Indeed, theoretical models have shown that stochastic but heritable epigenetic variation can be adaptive under changing environments (Feinberg & Irizarry, 2010).…”

Insects Provide Unique Systems to Investigate How Early-Life Experience Alters the Brain and Behavior

“…DNA methylation and histone post-translational modifications are the most wellstudied among these mechanisms (Smallwood and Kelsey, 2012;Paredes et al, 2016). Not all insects possess appreciable levels of DNA methylation (Deobagkar, 2018;Deshmukh et al, 2018), but some, including many social insects, do (Li-Byarlay, 2016;Yagound et al, 2020). Some studies show that developmental experience-induced changes in DNA methylation impact adult behavioral phenotypes (Linksvayer et al, 2012;Patalano et al, 2012;Weiner and Toth, 2012;Yan et al, 2014;Alvarado et al, 2015).…”