Local adaptation shapes metabolic diversity in the global population of Arabidopsis thaliana

The biosynthesis, structure and accumulation of secondary metabolites in plants are largely controlled by genetic factors, which can vary substantially among genotypes within a species. Here we studied a global population of Arabidopsis thaliana accessions for qualitative and quantitative variation in volatile and non-volatile secondary metabolites using essentially untargeted metabolomics. Genome-wide association (GWA) mapping revealed that metabolic variation mainly traces back to genetic variation in dedicated biosynthesis genes. Effect sizes of genetic variants, estimated by a Bayesian procedure, indicate that most of the genetic variation in the accumulation of secondary metabolites is explained by large-effect genes and defined by multiple polymorphisms. The various genetic variants resulted from independent mutation events and combined into distinctive haplotypes, which are representative for specific geographical regions. A strong relationship between the effect-size of regulatory loci, their allele frequencies and fixation index indicates that selection forces discriminate between haplotypes, resulting in different phytochemical profiles. Finally, we demonstrate that haplotype frequencies deviate from neutral theory predictions, suggesting that metabolic profiles are shaped by local adaptation and co-evolution of independent loci.