CONICET | Buscador de Institutos y Recursos Humanos

Objectives: To determine genetic differences between agriculturalist and hunter-gatherer southern Native American populations for selected metabolism-related markers and to test whether Neel?s thrifty genotype hypothesis (TGH) could explain the genetic patterns observed in these populations.Materials and methods: 375 Native South American individuals from 17 populations were genotyped using six markers (APOE rs429358 and rs7412; APOA2 rs5082; CD36rs3211883; TCF7L2 rs11196205; and IGF2BP2 rs11705701). Additionally, APOEgenotypes from 39 individuals were obtained from the literature. AMOVA, main effects, and gene-gene interaction tests were performed.Results: We observed differences in allele distribution patterns between agriculturalists and hunter-gatherers for some markers. For instance, between-groups component of genetic variance (FCT) for APOE rs429358 showed strong differences in allelic distributions between hunter-gatherers and agriculturalists (P = 0.00196). Gene-gene interaction analysis indicated that the APOE E4/CD36 TT and APOE E4/IGF2BP2 A carrier combinations occur at a higher frequency in hunter-gatherers, but this combination is not replicated in archaic (Neanderthal and Denisovan) and ancient (Anzick, Saqqaq, Ust-Ishim, Mal´ta) hunter-gatherer individuals.Discussion: A complex scenario explains the observed frequencies of the tested markers in hunter-gatherers. Different factors, such as pleotropic alleles, rainforest selective pressures, and population dynamics, may be collectively shaping the observed genetic patterns. We conclude that although TGH seems a plausible hypothesis to explain part of the data, other factors may be important in our tested populations.