Population epigenetic divergence exceeds genetic divergence in the Eastern oyster in the Northern Gulf of Mexico.

Populations may respond to environmental heterogeneity via evolutionary divergence or phenotypic plasticity. While evolutionary divergence occurs through DNA sequence differences among populations, plastic divergence among populations may be generated by changes in the epigenome. Here, we present the results of a genome-wide comparison of DNA methylation patterns and genetic structure among four populations of Eastern oyster () in the northern Gulf of Mexico. We used a combination of restriction site-associated DNA sequencing (RADseq) and reduced representation bisulfite sequencing (RRBS) to explore population structure, gene-wide averages of , and DNA methylation differences between oysters inhabiting four estuaries with unique salinity profiles. This approach identified significant population structure despite a moderately low (0.02) across the freshwater boundary of the Mississippi river, a finding that may reflect recent efforts to restore oyster stock populations. Divergence between populations in CpG methylation was greater than for divergence in , likely reflecting environmental effects on DNA methylation patterns. Assessment of CpG methylation patterns across all populations identified that only 26% of methylated DNA was intergenic; and, only 17% of all differentially methylated regions (DMRs) were within these same regions. DMRs within gene bodies between sites were associated with genes known to be involved in DNA damage repair, ion transport, and reproductive timing. Finally, when assessing the correlation between genomic variation and DNA methylation between these populations, we observed population-specific DNA methylation profiles that were not directly associated with single nucleotide polymorphisms or broader gene-body mean trends. Our results suggest that may use DNA methylation to generate environmentally responsive plastic phenotypes and that there is more divergence in methylation than divergence in allele frequencies.