Genetic signature of natural selection in first Americans

Abstract

When humans moved from Asia toward the Americas over 18,000 y ago and eventually peopled the New World they encountered a new environment with extreme climate conditions and distinct dietary resources. These environmental and dietary pressures may have led to instances of genetic adaptation with the potential to influence the phenotypic variation in extant Native American populations. An example of such an event is the evolution of the fatty acid desaturases (FADS) genes, which have been claimed to harbor signals of positive selection in Inuit populations due to adaptation to the cold Greenland Arctic climate and to a protein-rich diet. Because there was evidence of intercontinental variation in this genetic region, with indications of positive selection for its variants, we decided to compare the Inuit findings with other Native American data. Here, we use several lines of evidence to show that the signal of FADS-positive selection is not restricted to the Arctic but instead is broadly observed throughout the Americas. The shared signature of selection among populations living in such a diverse range of environments is likely due to a single and strong instance of local adaptation that took place in the common ancestral population before their entrance into the New World. These first Americans peopled the whole continent and spread this adaptive variant across a diverse set of environments.

Evolution of Hominin Polyunsaturated Fatty Acid Metabolism: From Africa to the New World

“…However prior analyses only had access to small Native American ancestry sample size [15,16] which did not facilitate a comprehensive examination of the genomic architecture of the FADS gene region in Native American ancestry populations. In addition, more recent studies suggest that the ancestral haplotype is under positive selection in the Greenlandic Inuit [17] and Native American populations [18], while the derived haplotype is under positive selection in African [15,16] and European populations [19]. These findings provide evidence that differential selection pressures that favor one FADS haplotype over another may play a critical role in the capacity of populations to adapt to regional environments.…”

“…The TMRCA of the derived haplotypes is within the modern-archaic human divergence [22], however the haplotype topography and tree (Figure 3, 4) indicate that the TMRCA should predate the divergence of these hominins. Since both the ancestral and derived haplotypes are under positive selection ( Figure 2) [15,[17][18][19], we are likely underestimating the TMRCA of the derived haplotypes. Positive selection causes a reduction in diversity of variants within a haplotype [71] and therefore a reduced TMRCA estimate.…”

“…Fumagalli et al [17] showed that the FADS region is under positive selection in the Figure 2). The results from Greenland [17], other Native American populations [18], and now Peru indicate that the ancestral haplotype was beneficial to ancestral populations that migrated to the Americas. Fumagalli et al [17] suggested that the ancestral haplotype is beneficial for cold weather adaptation by assisting with responding to dietary restricitions imposed by such a climate.…”

“…Therefore, it is plausible that the TMRCA of the derived haplotype is in fact older than the modern-archaic human divergence. Further, the differential selection pressures of the ancestral and derived haplotypes [15,[17][18][19] could then explain the global haplotype frequency distribution.…”

Population history and gene divergence in Native Mexicans inferred from 76 human exomes

“…One remarkable instance is FADS3, a gene in the FADS (fatty acid desaturases) genes cluster in chromosome 11, which also includes FADS1 and FADS2. These genes are involved in the metabolism of omega-3 polyunsaturated fatty acids, and have been found to harbor strong signals of positive selection in Arctic populations (Fumagalli et al 2015) and throughout the Americas (Amorim et al 2017). It has been proposed that this signal derives from a strong selective pressure on the ancestors present-day Native Americans (Amorim et al 2017) who had to adapt to extreme cold weather and food availability during the Beringia standstill (Tamm et al 2007).…”