Epigenomic divergence underlies sequence polymorphism and the evolutionary fate of duplicate paralogs in A. thaliana.

Processes affecting rates of sequence polymorphism are fundamental to molecular evolution and the evolutionary fate of gene duplicates. The relationship between gene activity and sequence polymorphism can influence the likelihood that functionally redundant gene copies are co-maintained in stable evolutionary equilibria versus other outcomes such as neo-functionalization. Here we investigate genic variation in epigenome-associated polymorphism rates in Arabidopsis thaliana and consider whether these affect the evolution of gene duplicates. We compared the frequency of sequence polymorphism and patterns of genetic differentiation between genes classified by exon methylation patterns: unmethylated (unM), gene-body methylated (gbM), and transposon-like methylated (teM) states, which reflect divergence in gene expression. We found that the frequency of polymorphism was higher in teM (transcriptionally repressed, tissue-specific) genes and lower in gbM (active, constitutively expressed) genes. Comparisons of gene duplicates were largely consistent with genome-wide patterns - gene copies that exhibit teM tend to accumulate higher sequence polymorphism, evolve faster, and are in chromatin states associated with reduced DNA repair. This relationship between expression, the epigenome, and polymorphism may lead to the breakdown of equilibrium states that would otherwise maintain genetic redundancies. Epigenome-mediated polymorphism rate variation may therefore aid the pseudogenization of duplicate paralogs or increase the evolution of novel gene functions in duplicate paralogs maintained over evolutionary time. ### Competing Interest Statement The authors have declared no competing interest.