The Evolutionary Complexities of DNA Methylation in Animals: From Plasticity to Genetic Evolution

Abstract

The importance of DNA methylation in plastic responses to environmental change and evolutionary dynamics is increasingly recognized. Here, we provide a Perspective piece on the diverse roles of DNA methylation on broad evolutionary timescales, including (i) short-term transient acclimation, (ii) stable phenotypic evolution, and (iii) genomic evolution. We show that epigenetic responses vary along a continuum, ranging from short-term acclimatory responses in variable environments within a generation to long-term modifications in populations and species. DNA methylation thus unlocks additional potential for organisms to rapidly acclimate to their environment over short timeframes. If these changes affect fitness, they can circumvent the need for adaptive changes at the genome level. However, methylation has a complex reciprocal relationship with genetic variation as it can be genetically controlled, yet it can also induce point mutations and contribute to genomic evolution. When habitats remain constant over many generations, or populations are separated across habitats, initially plastic phenotypes can become hardwired through epigenetically facilitated mutagenesis. It remains unclear under what circumstances plasticity contributes to evolutionary outcomes, and when plastic changes will become permanently encoded into genotype. We highlight how studies investigating the evolution of epigenetic plasticity need to carefully consider how plasticity in methylation state could evolve among different evolutionary scenarios, the possible phenotypic outcomes, its effects on genomic evolution, and the proximate energetic and ultimate fitness costs of methylation. We argue that accumulating evidence suggests that DNA methylation can contribute toward evolution on various timescales, spanning a continuum from acclimatory plasticity to genomic evolution.

Keywords: DNA methylation; adaptation; epigenetics; evolution; mutation; plasticity.

Fig. 1.

DNA methylation can contribute toward rapid, transient acclimation. (A) Summary of five selected studies showing rapid (<4 days) epigenetic responses to environmental manipulation. (B) Hypothetical relationships between the rate of environmental change and corresponding plastic responses within a generation. Developmental critical periods are represented by the grey-shaded background. (i) The environment changes at a rate that permits plastic epigenetic responses to keep pace, with organisms able to respond to environmental cues rapidly and appropriately. (ii) The environment changes too rapidly or unpredictably for plastic methylation changes to keep up (e.g., Stajic et al. 2022) which makes plasticity costly and/or maladaptive. (iii) The environment remains relatively stable and does not elicit plastic responses. (iv) The environment changes at a speed where DNA methylation can respond, but environmental cues are not accurately interpreted, or plastic responses are maladaptive. (v) Developmental plasticity leads to developmental determination of methylation state.

Fig. 2.

DNA methylation can contribute toward stable phenotypic variation. (A) A synthesis on salinity acclimation and adaptation in three-spine stickleback. (i) Hu and Barrett (2023) found that repeated evolution of stickleback from ancestral marine to derived freshwater environments is associated with altered DNA methylation. There was no significant trend toward parallelism versus non-parallelism, indicating that different methylation changes in different populations can achieve the same adaptive response to salinity. Lollipops signify methylated sites. (ii) The studies by Artemov et al. (2017) and Hu and Barrett (2023) found that freshwater populations had a greater capacity for plasticity during saltwater challenges, possibly compensating for reduced genetic variation due to bottlenecks. Heckwolf et al. (2020) reared stickleback from brackish environments in lower salinities, causing their methylation state to increasingly resemble that of locally adapted stickleback over generations. (B) Scenarios that would maintain methylation state leading to stable phenotypic variation. (i) Organisms experience the same environment as their parents leading to perpetuation of their methylation state. (ii) Developmental plasticity determines methylation state and consequent phenotypes. Two different individuals' phenotypes and environments are denoted by the different line types (solid and dotted). (iii) Stabilizing selection acts to maintain methylation state. (iv) Populations or species neutrally diverge through (epi)genetic drift.

Fig. 3.

The reciprocal relationship between DNA methylation and genetic variation. (A) Marshall et al. (2023) characterized methylation differences (lollipops) between sexes and castes of buff-tailed bumblebee. Diploid queens and female worker bees had more similar methylation profiles than haploid males. Sites with higher methylation tended to be zero-fold degenerate sites (i.e., sites that will always lead to a codon change when mutation occurs). This suggests that these sites are more likely to mutate, leading to altered protein amino acid sequence. (B) Interactions between genetic and epigenetic variation that could contribute to evolution. (i) Genetic variants such as SNPs can regulate methylation at proximal or distant CpG sites, leading to genetic control over the methylation state. (ii) DNA methylation can induce point mutations at methylated sites over time, particularly if these mutations are not corrected by DNA repair. (iii) DNA methylation suppresses TE activity whereas hypomethylation increases their movement, leading to structural variation.