Potential Role of DNA Methylation as a Driver of Plastic Responses to the Environment Across Cells, Organisms, and Populations

Abstract

There is great interest in exploring epigenetic modifications as drivers of adaptive organismal responses to environmental change. Extending this hypothesis to populations, epigenetically driven plasticity could influence phenotypic changes across environments. The canonical model posits that epigenetic modifications alter gene regulation and, subsequently impact phenotypes. We first discuss origins of epigenetic variation in nature, which may arise from genetic variation, spontaneous epimutations, epigenetic drift, or variation in epigenetic capacitors. We then review and synthesize literature addressing three facets of the aforementioned model: (i) causal effects of epigenetic modifications on phenotypic plasticity at the organismal level, (ii) divergence of epigenetic patterns in natural populations distributed across environmental gradients, and (iii) the relationship between environmentally induced epigenetic changes and gene expression at the molecular level. We focus on DNA methylation, the most extensively studied epigenetic modification. We find support for environmentally associated epigenetic structure in populations and selection on stable epigenetic variants, and that inhibition of epigenetic enzymes frequently bears causal effects on plasticity. However, there are pervasive confounding issues in the literature. Effects of chromatin-modifying enzymes on phenotype may be independent of epigenetic marks, alternatively resulting from functions and protein interactions extrinsic of epigenetics. Associations between environmentally induced changes in DNA methylation and expression are strong in plants and mammals but notably absent in invertebrates and non-mammalian vertebrates. Given these challenges, we describe emerging approaches to better investigate how epigenetic modifications affect gene regulation, phenotypic plasticity, and divergence among populations.

DNA methylation correlates with transcriptional noise in response to elevated pCO2in the eastern oyster (Crassostrea virginica)

“…We found clear evidence of DNA methylation reducing gene expression variability, or transcriptional noise, in a sex-specific manner in response to elevated pCO 2 . These findings align with the growing consensus that gene body methylation may not have a direct regulatory role in gene-level expression, but instead functions to broadly reduce transcriptional variation across the genome [32,50,51]. Additionally, differences in gene activity and methylation patterns between female and male oysters highlight the need to examine how OA may affect reproduction differently in females and males [21], and underscore the cell- and tissue-specificity of DNA methylation [52,53].…”

“…Although there is limited evidence for DNA methylation driving differential gene expression, it is possible that methylation may change transcriptional opportunities. Sparse methylation may allow for exon skipping or access to alternative start sites, thereby modifying gene expression and phenotype [31,32,55]. We observed that elevated pCO 2 elicits alternative splicing, although environmentally-responsive splicing accounted for a small proportion for the total splicing variance.…”

“…Given that the functional role of DNA methylation in marine invertebrates remains unclear [32], we leveraged whole genome, transcript-level data to conduct the first extensive assessment of DNA methylation-gene activity relationships in response to elevated pCO 2 in Crassostrea spp. gonad tissues to our knowledge.…”

“…DNA methylation can change expression of genes by altering binding of transcriptional machinery and can affect variability of transcription [30]. Changes in methylation are thought to be associated with phenotypic changes, with several examples of this connection illustrated in mammalian literature [32]. Methylomes (i.e.…”

“…Where gene expression has been used as a proxy for plasticity, molluscan studies report no relationship between differential gene expression and genes with differential methylation in response to environmental stress [36,39,42–44]. This phenomenon extends beyond molluscan OA literature to other marine invertebrate taxa [32]. One exception is Dang et al [41], which found significant overlap between differentially expressed genes and differentially methylated genes in juvenile C. hongkongensis after exposure to OA conditions as larvae.…”