Genomic diversity and post-admixture adaptation in the Uyghurs

Abstract

Population admixture results in genome-wide combinations of genetic variants derived from different ancestral populations of distinct ancestry, thus providing a unique opportunity for understanding the genetic determinants of phenotypic variation in humans. Here, we used whole-genome sequencing of 92 individuals with high coverage (30–60×) to systematically investigate genomic diversity in the Uyghurs living in Xinjiang, China (XJU), an admixed population of both European-like and East-Asian-like ancestry. The XJU population shows greater genetic diversity, especially a higher proportion of rare variants, compared with their ancestral source populations, corresponding to greater phenotypic diversity of XJU. Admixture-induced functional variants in EDAR were associated with the diversity of facial morphology in XJU. Interestingly, the interaction of functional variants between SLC24A5 and OCA2 likely influences the diversity of skin pigmentation. Notably, selection has seemingly been relaxed or canceled in several genes with significantly biased ancestry, such as HERC2 – OCA2 . Moreover, signatures of post-admixture adaptation in XJU were identified, including genes related to metabolism (e.g. CYP2D6 ), digestion (e.g. COL11A1 ), olfactory perception (e.g. ANO2 ) and immunity (e.g. HLA ). Our results demonstrated population admixture as a driving force, locally or globally, in shaping human genetic and phenotypic diversity as well as in adaptive evolution.

Lineage-specific positive selection on ACE2 contributes to the genetic susceptibility of COVID-19

“…Chromosome-wide genetic diversity was estimated within sliding windows of 10 kb in length, advanced by 5 kb by estimators of nucleotide diversity ( θ π ) and numbers of segregating sites ( θ K ) using publicly available software [ 60 ]. Tajima's D statistics [ 27 ], Fay and Wu's H statistics [ 37 , 38 ], H12 statistics [ 39 , 61 , 62 ], Fu and Li's D statistics [ 43 ], and Fu and Li's F statistics [ 43 ] were calculated in the same way.…”

Editorial: Forensic investigative genetic genealogy and fine-scale structure of human populations

“…They followingly migrated out of Africa around 50 thousand years ago and evolved in concert with the complicated interplay of gene flow and adaptive selection during the peopling of Eurasia, Oceania, and America ( Bergstrom, et al, 2020 ; Wang et al, 2021a ). Genomic studies have demonstrated the pervasiveness of population differentiation and genetic admixture between long-isolated ethnic groups ( Bergstrom et al, 2020 ; Pan et al, 2022 ). Extensive population bottleneck, adaptive evolution in changing environments, and introgression from archaic hominins further shaped the complicated patterns of human genetic heritage.…”

“…There is increasing evidence to suggest that the differences in the susceptibility of many common and rare diseases are primarily attributed to human populations’ diverse cultural, environmental, demographic, and genetic histories. The comprehensive understanding of fine-scale population evolutionary history will gradually change our understanding of the genetic architecture of diseases ( Timpson et al, 2018 ; Benton et al, 2021 ; Pan et al, 2022 ). Thus, there is an urgent need to expand genetic research to populations with different ancestries.…”

Admixture-introduced complex landscape of genetic diversity contributed to the extensive Southwestern Chinese ethnolinguistic diversity

“…In addition to large-scale clinical genomic cohorts that have advanced the understanding of genetic determinants of disease susceptibility and genetic background of Han Chinese populations, many molecular anthropological and evolutionary genetic studies started to focus on the genetic diversity of ethnolinguistically diverse populations in China, such as the characterization of population history and biological adaptation of Tibetan [11][12][13][14][15] and Sherpa [16] from the Tibetan Plateau and the dissection of Eurasian admixture signature in Uyghur [17] and Hui [18]. However, we should note that most previous genetic studies were conducted based on forensic-related genetic markers [Short Tandem Repeats (STRs), Insertion/Deletions (InDels), Micro-Haplotypes, ancestry-informative SNPs (AISNPs), and other Xor Y-linked markers] or lower-density SNPs (50K ~ 100K) in the merged dataset [19][20][21].…”