Whole-genome sequencing of ethnolinguistic diverse northwestern Chinese Hexi Corridor people from the 10K_CPGDP project suggested the differentiated East-West genetic admixture along the Silk Road and their biological adaptations

Abstract

The ancient Silk Road served as the main connection between East and West Eurasia for several centuries. At any rate, the genetic exchange between populations along the ancient Silk Road was likely to leave traces on the contemporary gene pool of local people in Northwest China, which was the passage of the Northern Silk Road. However, genetic sources from northwestern China are under-represented in the current population-scale genomic database. To characterize the genetic architecture and adaptative history of the Northern Silk Road ethnic populations, we performed whole-genome sequencing on 126 individuals from six ethnolinguistic groups (Tibeto-Burman (TB)-speaking Tibetan, Mongolic (MG)-speaking Dongxiang/Tu/eastern Yugur, and Turkic (TK)-speaking Salar/western Yugur) living in Gansu and Qinghai in the 10K Chinese people Genomic Diversity Project (10K_CPGDP). We observed ethnicity-related differentiated population structures among these geographically close Northwest Chinese populations, that is, Salar and Tu people showed a close affinity with southwestern TB groups, and other studied populations shared more alleles with MG and Tungusic groups. Overall, the patterns of genetic clustering were not consistent with linguistic classifications. We estimated that Dongxiang, Tibetan, and Yugur people inherited more than 10% West Eurasian ancestry, much higher than that of Salar and Tu people (< 7%). Hence, the difference in the proportion of West Eurasian ancestry has primarily contributed to the genetic divergence of geographically close Northwest Chinese populations. The signatures of natural selection were identified in genes associated with cardiovascular system diseases or lipid metabolism related to triglyceride levels (e.g., PRIM2, PDE4DIP, NOTCH2, DDAH1, GALNT2, and MLIP) and developmental and neurogenetic diseases (e.g., NBPFs 8/9/20/25P, etc.). Moreover, the EPAS1 gene, a transcription factor regulating hypoxia response, showed relatively high PBS values in our studied groups. The sex-biased admixture history, in which the West Eurasian ancestry was introduced primarily by males, was identified in Dongxiang, Tibetan, and Yugur populations. We determined that the eastern-western admixture occurred ~783-1131 years ago, coinciding with the intensive economic and cultural exchanges during the historic Trans-Eurasian cultural exchange era.

The complex genetic landscape of southwestern Chinese populations contributed to their extensive ethnolinguistic diversity

“…We should also pay attention to the fact that the accurate IBD segment estimation and local ancestry calls can influence the accuracy of the estimates of historical population size (Browning and Browning, 2015;Browning et al, 2018). Furthermore, including more representative geographically different Guizhou people and analyzing wholegenome sequencing data combined with the PSMC, FitCoal, MSMC2, or SMC++ should be conducted to validate these observed patterns in the following large-scale genome sequencing projects, such as the 10K Chinese People Genomic Diversity Project (10K_CPGDP) (Schiffels and Durbin, 2014;He et al, 2023b;Hu et al, 2023).…”

Editorial: Full landscape of human genomic diversity and its impact on precision medicine

“…Recent genomic projects like United Kingdom Biobank 100 K and TopMed have certainly advanced our understanding of the genetic bases of human diseases and complex traits ( Taliun et al, 2021 ; Rubinacci et al, 2023 ). However, to truly grasp the genetic similarities and differences among continental populations from both evolutionary and medical perspectives, we need to embark on further studies, such as the 10K Chinese People Genomic Diversity Project (10K_CPGDP) ( He et al, 2023 ).…”

Multiple Human Population Movements and Cultural Dispersal Events Shaped the Landscape of Chinese Paternal Heritage

“…Recent research utilized genome-wide SNP microarrays to analyze the genomic diversity and population history of various Sino-Tibetan, Mongolic, Tungusic, Turkic, Tai-Kadai, and Hmong-Mien groups ( Feng et al 2017 ; He et al 2022 ; Wang et al 2022 ; He et al 2023b ; Sun et al 2023 ; Li et al 2024 ). Additionally, the rise of whole-genome sequencing studies has expanded, featuring projects, such as the Westlake BioBank for Chinese, the NyuWa genome resource, the China Metabolic Analytics Project, and the 10K Chinese People Genomic Diversity Project (10K_CPGDP; Cao et al 2020 ; Zhang et al 2021a ; Cong et al 2022 ; Cheng et al 2023 ; He et al 2023c ). These efforts enhance our understanding of the genetic diversity, demographic history, and genetic architecture of complex traits and diseases in ethnolinguistically distinct Chinese populations from an autosomal perspective, suggesting a further exploration of their fine-scale genetic structure from both uniparental and population-scale project perspectives.…”

“…Recent increases in genomic resources from Chinese populations have highlighted the gap in our understanding of the paternal genetic diversity among ethnic minorities, which lags significantly behind that of Han Chinese and other global populations ( Karmin et al 2022 ). To address this issue, we launched the 10K_CPGDP by employing anthropologically informed sampling strategies ( He et al 2023c ). Additionally, we introduce the YanHuang cohort (YHC) genomic resource that includes new Y-chromosome sequences from ethnolinguistically diverse ethnic minorities and integrates data from the 10K_CPGDP.…”