Epigenetic inheritance mediates phenotypic evolution in natural populations

Genetic variation is regarded as a prerequisite for evolution. Theoretical models suggest epigenetic information inherited independently of DNA sequence can also enable evolution. However, whether epigenetic inheritance mediates phenotypic evolution in natural populations is unknown. Here we show that natural epigenetic DNA methylation variation in gene bodies regulates genes expression, and thereby influences the natural variation of complex traits in Arabidopsis thaliana. Notably, the effects of methylation variation on phenotypic diversity and gene expression variance are comparable with those of DNA sequence polymorphism. We also identify methylation epialleles in numerous genes associated with environmental conditions in native habitats, suggesting that intragenic methylation facilitates adaptation to fluctuating environments. Our results demonstrate that methylation variation fundamentally shapes phenotypic diversity in natural populations and provides an epigenetic basis for adaptive Darwinian evolution independent of genetic polymorphism. Bisulfite and RNA sequencing was performed using one h1;met1+/- plant and six h1 plants segregated from h1;met1+/- (h1;met1+/+). For bisulfite sequencing, we constructed one bs-seq library per plant. To profile RNA expression, we constructed three RNA-seq libraries per h1;met1+/- plant (3 replicates), and one RNA-seq library for h1;met1+/-.