Disentangling signatures of selection before and after European colonization in Latin Americans

Abstract

Throughout human evolutionary history, large-scale migrations have led to intermixing (i.e., admixture) between previously separated human groups. While classical and recent work have shown that studying admixture can yield novel historical insights, the extent to which this process contributed to adaptation remains underexplored. Here, we introduce a novel statistical model, specific to admixed populations, that identifies loci under selection while determining whether the selection likely occurred post-admixture or prior to admixture in one of the ancestral source populations. Through extensive simulations we show that this method is able to detect selection, even in recently formed admixed populations, and to accurately differentiate between selection occurring in the ancestral or admixed population. We apply this method to genome-wide SNP data of ~4,000 individuals in five admixed Latin American cohorts from Brazil, Chile, Colombia, Mexico and Peru. Our approach replicates previous reports of selection in the HLA region that are consistent with selection post-admixture. We also report novel signals of selection in genomic regions spanning 47 genes, reinforcing many of these signals with an alternative, commonly-used local-ancestry-inference approach. These signals include several genes involved in immunity, which may reflect responses to endemic pathogens of the Americas and to the challenge of infectious disease brought by European contact. In addition, some of the strongest signals inferred to be under selection in the Native American ancestral groups of modern Latin Americans overlap with genes implicated in energy metabolism phenotypes, plausibly reflecting adaptations to novel dietary sources available in the Americas.

Hunter-gatherer admixture facilitated natural selection in Neolithic European farmers

“…( Figure 2C ). Bias in LAD analysis at the HLA locus has been suggested to be expected in the direction of the source ancestry with higher diversity, 48 unlike what we observe here. We also run ancestryHMM on the human reference genome to test the hypothesis of biased mapping but find that the reference is inferred to have both Neolithic and Mesolithic ancestry at this locus ( Figure 2C ).…”

“…This is contrary to the idea that the pathogen load in Neolithic populations was solely driven by increased population density and proximity to zoonotic vectors via animal husbandry. On the other hand, although examples of putative adaptive admixture involving the MHC have been previously described, 48 , 53 , 54 no clear link between the alleles under selection within this region and a specific pathogen has been identified.…”

Balancing selection on genomic deletion polymorphisms in humans

“…These low-frequency functional variants are considered to be in the process of being eliminated from the population by negative selection ( Gibson, 2018 ; Lettre, 2014 ; Zeng et al, 2018 ). Nevertheless, an increasing number of studies are showing that more complex evolutionary histories ( Benton et al, 2021 ; Mathieson and Mathieson, 2018 ) involving introgression from archaic hominins ( McArthur et al, 2020 ), geography-specific adaptation ( Hamid et al, 2021 ; Lachance and Tishkoff, 2013 ; Mendoza-Revilla et al, 2021 ), negative selection ( Zeng et al, 2018 ), and polygenic selection ( Barghi et al, 2020 ; Berg and Coop, 2014 ; Pritchard et al, 2010 ; Sella and Barton, 2019 ) may explain the allele frequencies of variants associated with complex diseases. In this context, we aim to test the hypothesis that balancing selection is a considerable force in shaping the allele frequencies of extant functional deletions in the human genome.…”

Balancing selection on genomic deletion polymorphisms in humans

“…These low-frequency functional variants are considered to be in the process of being eliminated from the population by negative selection (Gibson, 2018;Lettre, 2014;Zeng et al, 2018). Nevertheless, an increasing number of studies are showing that more complex evolutionary histories (Benton et al, 2021;Mathieson & Mathieson, 2018), including introgression from archaic hominins (McArthur et al, 2020), geography-specific adaptation (Hamid et al, 2021;Lachance & Tishkoff, 2013;Mendoza-Revilla et al, 2021), negative selection (Zeng et al, 2018), and polygenic selection (Barghi et al, 2020;Berg & Coop, 2014;Pritchard et al, 2010;Sella & Barton, 2019) may explain the allele frequencies of variants associated with complex diseases. In this context, we aim to test the hypothesis that balancing selection is a considerable force in shaping the allele frequencies of extant functional deletions in the human genome.…”