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A central problem when studying adaptation to a new environment is theinterplay between genetic variation and phenotypic plasticity. Arabidopsisthaliana has colonized a wide range of habitats across the world and it istherefore an attractive model for studying the genetic mechanisms underlyingenvironmental adaptation 4,5. Here, we used publicly available data from twocollections of A. thaliana accessions, covering the native range of thespecies, to identify loci associated with differences in climates at thesampling sites. To address the confounding between geographic location, climateand population structure, a new genome-wide association analysis method wasdeveloped that facilitates detection of potentially adaptive loci where thealternative alleles display different tolerable climate ranges. Sixteen novelsuch loci, many of which contained candidate genes with amino acid changes,were found including a strong association between Chromomethylase 2 (CMT2) andvariability in seasonal temperatures. The reference allele dominated in areaswith less seasonal variability in temperature, and the alternative allele,which disrupts genome-wide CHH-methylation, existed in both stable and variableregions. Our results link natural variation in CMT2, and differentialgenome-wide CHH methylation, to the distribution of A. thaliana accessionsacross habitats with different seasonal temperature variability. They alsosuggest a role for genetic regulation of epigenetic modifications in naturaladaptation, potentially through differential allelic plasticity, and illustratethe importance of re-analyses of existing data using new analytical methods toobtain a more complete understanding of the mechanisms contributing toadaptation.

Natural CMT2 variation is associated with genome-wide methylation changes and temperature adaptation