Standing covariation between genomic and epigenomic patterns as source for natural selection in wild strawberry plants

Adaptive evolution is generally thought to be the result of natural selection predominantly acting upon pre-existing DNA sequence polymorphisms through gene-environment interactions. Epigenetic inheritance is, however, recently considered an additional molecular force driving adaptive evolution independent of DNA sequence variation. Through comparative analyses of genome-wide genetic (SNPs) and epigenetic (DMCs) variation of wild strawberry plants raised under distinct drought settings, we demonstrate intermediate levels of genome-wide covariation between SNPs and DMCs. Cases of high SNP-DMC covariation were significantly associated with (i) applied stress, (ii) non-adaptive SNPs, and (iii) solitary DMCs (as opposed to DMC islands). We also found that DMCs, drought-responsive DMCs in particular, typically co-vary with hundreds of SNPs, indicating high genomic redundancy as a basis for polygenic adaptation. Our findings suggest that stress-responsive DMCs initially co-vary with many associated SNPs under increased environmental stress (cfr. co-gradient plasticity), and that natural selection acting upon these SNPs subsequently reduce standing covariation with stress-responsive DMCs. In addition, the degree of covariation between SNPs and DMCs appears independent of their respective genomic distance, indicating that trans-acting associations between SNPs and DMCs are as likely as cis-acting associations. Our study is in favor of DNA methylation profiles representing complex quantitative traits rather than independent evolutionary forces, but further research is required to fully rule out SNP-independence of genome-wide DMCs. We provide a conceptual framework for polygenic regulation and adaptation shaping genome-wide methylation patterns.