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. Although 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 human leukocyte antigen 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.

Population Genetics and Signatures of Selection in Early Neolithic European Farmers

“…This method is a modification of the admixture-aware linear model-based test developed by Mathieson et al (2015) ; however, our test is specifically designed for two population admixture scenarios. AIMLESS is similar to other likelihood ratio test (LRT)-based tests ssuch as AdaptMix ( Mendoza-Revilla et al 2021 ) and Ohana ( Cheng et al 2022 ) but does not rely on a priori ancestry estimation and determines the mixture components for the ancestries considered for each single-nucleotide polymorphism (SNP) independently instead of using a genome-wide estimate.…”

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.…”

The immunogenetic impact of European colonization in the Americas

“…The recency of colonization may thus mask the detection of selected genomic regions (Schrider and Kern, 2017;Vargas et al, 2022). While recent analyses have identified selection signals possibly linked to colonization by modeling allele frequency deviations considering admixture, the candidate loci exhibit very large selection coefficients (~0.15-0.2) that enhance statistical power (Zheng and Wiehe, 2019;Mendoza-Revilla et al, 2022). Taking these limitations into account, pathogen-driven selection acting on post-contact immunity genes in Indigenous peoples of the Americas would thus be best identified by population genetic methods that can detect soft selective sweeps, comparisons between ancient and contemporary genomes, comparisons between worldwide populations, and polygenic approaches, wherein selection signals are observed cumulatively across immune gene classes and pathways.…”

“…Previous studies investigating admixed Latin American populations in Colombia, Mexico, Peru, and Puerto Rico suggested that selection may have acted upon admixed alleles from Africa, particularly within the HLA region and in pathways involved in inflammation, such as the innate and adaptive immune response (Norris et al, 2020). Another study on five Latin American cohorts showed that HLA alleles under putative selection carry an overrepresentation of African ancestry (Ongaro et al, 2021;Mendoza-Revilla et al, 2022). This study used deviations from neutrality in the expected allele frequency in admixed populations, given known allele frequencies in the source populations, to allow detection of selected regions despite high levels of admixture.…”