Epigenetic inheritance mediates phenotypic diversity in natural populations

Genetic variation is regarded as a prerequisite for evolution. In principle, epigenetic information inherited independently of DNA sequence can also enable evolution, but whether this occurs in natural populations is unknown. Here we show that natural epigenetic DNA methylation polymorphism in Arabidopsis thaliana gene bodies regulates gene expression and influences the variation of complex traits: fitness under heat and drought, flowering time, and accumulation of diverse minerals. The phenotypic effects of DNA methylation and local DNA sequence polymorphism are comparable, but they operate through largely distinct gene sets. Our epigenetic association analyses directly identify the relevant gene more frequently than genetic associations, likely due to reduced linkage disequilibrium. We identify numerous associations between methylation epialleles and diverse environmental conditions in native habitats, suggesting that intragenic methylation facilitates adaptation to fluctuating environments. Overall, our results demonstrate that epigenetic methylation variation fundamentally shapes phenotypic diversity in natural populations.