Variation patterns at nutrition-related genes: insight into human adaptations to dietary changes

Several dietary shifts have occurred in the human lineage accompanying transitions to high-quality diets, the adoption of meat eating, food processing and cooking, and facilitating the evolution of energetically expensive brains. Adaptations to new nutritional resources have thus strongly contributed to shape the genome of human ancestors and of H. sapiens, influencing a variety of traits, being often related to crucial biological/cultural innovations, and introducing novel challenges to human metabolism. The relatively recent human occupation of a vast range of environments, in which populations encountered ever new and demanding nutritional landscapes, further boosted the rate of these dietary changes, producing dramatic and still on-going modifications in human diets. Selective forces associated to food availability have thus varied over a geographical scale, driving adaptations in response to local environmental/cultural pressures, the latter having played a key role in the evolution of human diets, mainly through plants and animals domestication. Accordingly, adaptive genetic variants have been plausibly selected in human groups exposed to novel dietary environments during the last 60,000 years, even though cultural/dietary changes are ever-accelerating since the Neolithic Transition, leading to possible maladaptation in contemporary populations. Exploring the genetic bases of nutrition-related adaptations will thus enable to shed light not only on some of the main mechanisms that have shaped the human genome, but also on those contributing to common metabolic diseases affecting present-day societies. To detect signatures of these adaptations, genetic variation at more than 40 nutrition-related genes selected according to their major role in functional pathways associated to processing and digestion of food, or associated with metabolic diseases, was investigated in 14 populations from the phase I of the 1000 Genomes project. For this purpose, information about several thousands of SNPs was retrieved from sequence data and used to assess derived allele frequency, differentiation among the examined groups and genetic structure at the investigated loci. Different neutrality tests were used to shortlist the best candidate genes potentially responsible for moderate to strong patterns of dietary adaptation in the studied populations. Further understanding of the mechanisms of action of these genes promises to give new insight into the recent history of human adaptation and its implication on the epidemiology of metabolic diseases.