RT Journal Article SR Electronic T1 Natural CMT2 variation is associated with genome-wide methylation changes and temperature seasonality JF bioRxiv FD Cold Spring Harbor Laboratory SP 004119 DO 10.1101/004119 A1 Xia Shen A1 Jennifer De Jonge A1 Simon Forsberg A1 Mats Pettersson A1 Zheya Sheng A1 Lars Hennig A1 Örjan Carlborg YR 2014 UL http://biorxiv.org/content/early/2014/10/03/004119.abstract AB As Arabidopsis thaliana has colonized a wide range of habitats across the world it is an attractive model for studying the genetic mechanisms underlying environmental adaptation. Here, we used public data from two collections of A. thaliana accessions to associate genetic variability at individual loci with differences in climates at the sampling sites. We use a novel method to screen the genome for plastic alleles that tolerate a broader climate range than the major allele. This approach reduces confounding with population structure and increases power compared to standard genome-wide association methods. Sixteen novel loci were found, including an association between Chromomethylase 2 (CMT2) and temperature seasonality where the genome-wide CHH methylation was different for the group of accessions carrying the plastic allele. Cmt2 mutants were shown to be more tolerant to heat-stress, suggesting genetic regulation of epigenetic modifications as a likely mechanism underlying natural adaptation to variable temperatures, potentially through differential allelic plasticity to temperature-stress.AUTHOR SUMMARY 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. Here, we study two collections of A. thaliana accessions from across Eurasia to identify loci associated with differences in climates at the sampling sites. A new genome-wide association analysis method was developed to detect adaptive loci where the alleles tolerate different climate ranges. Sixteen novel such loci were found including a strong association between Chromomethylase 2 (CMT2) and temperature seasonality. The reference allele dominated in areas with less seasonal variability in temperature, and the alternative allele existed in both stable and variable regions. Our results thus link natural variation in CMT2 and epigenetic changes to temperature adaptation. We showed experimentally that plants with a defective CMT2 gene tolerate heat-stress better than plants with a functional gene. Together this strongly suggests a role for genetic regulation of epigenetic modifications in natural adaptation to temperature and illustrates the importance of re-analyses of existing data using new analytical methods to obtain deeper insights into the underlying biology from available data.