  A central problem when studying adaptation to a new environment is the
interplay between genetic variation and phenotypic plasticity. Arabidopsis
thaliana has colonized a wide range of habitats across the world and it is
therefore an attractive model for studying the genetic mechanisms underlying
environmental adaptation 4,5. Here, we used publicly available data from two
collections of A. thaliana accessions, covering the native range of the
species, to identify loci associated with differences in climates at the
sampling sites. To address the confounding between geographic location, climate
and population structure, a new genome-wide association analysis method was
developed that facilitates detection of potentially adaptive loci where the
alternative alleles display different tolerable climate ranges. Sixteen novel
such loci, many of which contained candidate genes with amino acid changes,
were found including a strong association between Chromomethylase 2 (CMT2) and
variability in seasonal temperatures. The reference allele dominated in areas
with less seasonal variability in temperature, and the alternative allele,
which disrupts genome-wide CHH-methylation, existed in both stable and variable
regions. Our results link natural variation in CMT2, and differential
genome-wide CHH methylation, to the distribution of A. thaliana accessions
across habitats with different seasonal temperature variability. They also
suggest a role for genetic regulation of epigenetic modifications in natural
adaptation, potentially through differential allelic plasticity, and illustrate
the importance of re-analyses of existing data using new analytical methods to
obtain a more complete understanding of the mechanisms contributing to
adaptation.
