Dietary adaptation of FADS genes in Europe varied across time and geography

Abstract

Fatty acid desaturase (FADS) genes encode rate-limiting enzymes for the biosynthesis of omega-6 and omega-3 long chain polyunsaturated fatty acids (LCPUFAs). This biosynthesis is essential for individuals subsisting on LCPUFAs-poor diets (e.g. plant-based). Positive selection on FADS genes has been reported in multiple populations, but its presence and pattern in Europeans remain elusive. Here, using ancient and modern DNA, we demonstrate that positive selection acted on the same FADS variants both before and after the advent of farming in Europe, but on opposite (i.e. alternative) alleles. Selection in recent farmers also varied geographically, with the strongest signal in Southern Europe. These varying selection patterns concur with anthropological evidence of varying diets, and with the association of farming-adaptive alleles with higher FADS1 expression and thus enhanced LCPUFAs biosynthesis. Genome-wide association studies reveal that farming-adaptive alleles not only increase LCPUFAs, but also affect other lipid levels and protect against several inflammatory diseases.