Human genetic admixture through the lens of population genomics

Abstract

Over the past 50 years, geneticists have made great strides in understanding how our species' evolutionary history gave rise to current patterns of human genetic diversity classically summarized by Lewontin in his 1972 paper, ‘The Apportionment of Human Diversity’. One evolutionary process that requires special attention in both population genetics and statistical genetics is admixture: gene flow between two or more previously separated source populations to form a new admixed population. The admixture process introduces ancestry-based structure into patterns of genetic variation within and between populations, which in turn influences the inference of demographic histories, identification of genetic targets of selection and prediction of complex traits. In this review, we outline some challenges for admixture population genetics, including limitations of applying methods designed for populations without recent admixture to the study of admixed populations. We highlight recent studies and methodological advances that aim to overcome such challenges, leveraging genomic signatures of admixture that occurred in the past tens of generations to gain insights into human history, natural selection and complex trait architecture. This article is part of the theme issue ‘Celebrating 50 years since Lewontin's apportionment of human diversity’.

Localizing post-admixture adaptive variants with object detection on ancestry-painted chromosomes

“…In this case, the model is unable to detect any ancestry-based patterns of selection because both ancestries are being equally selected. We have previously suggested and demonstrated this same result with other ancestry-based signatures of selection (Gopalan et al, 2022;Hamid et al, 2021).…”

“…We next sought to evaluate whether our method constitutes an improvement on the most commonly used method for detecting regions under selection for admixed populations.The ‘local ancestry outlier’ approach identifies regions that deviate from the genome-wide average ancestry proportion, which are hypothesized to be enriched for regions under selection (Bryc et al, 2010; Gopalan et al, 2022; Tang et al, 2007). We compared performance between ancestry outlier detection and our method by calculating precision and recall, including over a range of selection coefficients (Table 3 & Figure 3B-E).…”

“…Small amounts of gene flow or larger admixture may introduce advantageous alleles which then undergo positive selection. Such cases have been identified in diverse taxa, often termed adaptive introgression (Aguillon et al, 2022; Edelman & Mallet 2021; Hedrick, 2013; Hsieh et al, 2019; Huerta-Sánchez et al, 2014; Moran et al, 2021; Norris et al, 2015; Oziolor et al, 2019; Racimo et al, 2015; Whitney et al, 2006) or, in humans, post-admixture positive selection (Cuadros-Espinoza et al, 2022; Gopalan et al, 2022; Tang et al, 2007).…”

A geometric relationship of F 2 , F 3 and F 4 -statistics with principal component analysis

“…The complicated genetic structure observed in present-day human populations [8,9] is caused by the interplay of demographic and evolutionary processes with both discrete and continuous components [10][11][12][13][14]. In particular, populations are expected to differentiate if they are isolated from each other [15,16].…”

Celebrating 50 years since Lewontin's apportionment of human diversity

“…Broadening outward to the phenomenon of human genetic admixture more generally, Gopalan et al [26] review recent trends in demographic studies of the genetic history of admixed populations. As noted by Shen & Feldman [6], the classification system Lewontin sought to test did not have a clear role for genetic admixture, a phenomenon that has generated great interest in modern human population genetics.…”