53Theory predicts that environmental challenges can shape the composition of populations, which 54 is manifest at the molecular level. Previously, we demonstrated that oil pollution affected gene 55 expression patterns and altered genetic variation in natural populations of the foundation salt 56 marsh grass, Spartina alterniflora. Here, we used a reduced representation bisulfite sequencing 57 approach, epigenotyping by sequencing (epiGBS), to examine relationships among DNA 58 sequence, DNA methylation, gene expression, and exposure to oil pollution. We documented 59 genetic and methylation differentiation between oil-exposed and unexposed populations, 60suggesting that the Deepwater Horizon oil spill may have selected on genetic variation, and 61 either selected on epigenetic variation or induced particular epigenotypes and expression patterns 62 in exposed compared to unexposed populations. In support of the potential for differential 63 response to the Deepwater Horizon oil spill, we demonstrate genotypic differences in response to 64 oil under controlled conditions. Overall, these findings demonstrate genetic variation, epigenetic 65 variation and gene expression are correlated to exposure to oil pollution, which may all 66 contribute to the response to environmental stress. 67