Complementary genetic and epigenetic changes facilitate rapid adaptation to multiple global change stressors.

To persist under unprecedented rates of global change, populations can adapt or acclimate. However, how these resilience mechanisms interact, particularly the role of epigenetic variation in long-term adaptation, is unknown. To address this gap, we experimentally evolved the foundational marine copepod for 25 generations under ocean acidification, warming, and their combination and then measured epigenomic, genomic, and transcriptomic responses. We observed clear and consistent epigenomic and genomic divergence between treatments, with epigenomic divergence concentrated in genes related to stress response and the regulation of transposable elements. However, epigenetic and genetic changes were inversely related and occurred in different regions of the genome; levels of genetic differentiation (F) were up to 2.5× higher in regions where methylation did not differ between treatments compared to regions with significant methylation changes. This negative relationship between epigenetic and genetic divergence could be driven by local inhibition of one another or distinct functional targets of selection. Finally, epigenetic divergence was positively, though weakly, associated with gene expression divergence, suggesting that epigenetic changes may facilitate phenotypic change. Taken together, these results suggest that unique, complementary genetic and epigenetic mechanisms promote resilience to global change.