Combined Low-/High-Density Modern and Ancient Genome-Wide Data Document Genomic Admixture History of High-Altitude East Asians

Abstract

The Tibetan Plateau (TP) is considered to be one of the last terrestrial environments conquered by the anatomically modern human. Understanding of the genetic background of highland Tibetans plays a pivotal role in archeology, anthropology, genetics, and forensic investigations. Here, we genotyped 22 forensic genetic markers in 1,089 Tibetans residing in Nagqu Prefecture and collected 1,233,013 single nucleotide polymorphisms (SNPs) in the highland East Asians (Sherpa and Tibetan) from the Simons Genome Diversity Project and ancient Tibetans from Nepal and Neolithic farmers from northeastern Qinghai-Tibetan Plateau from public databases. We subsequently merged our two datasets with other worldwide reference populations or eastern ancient Eurasians to gain new insights into the genetic diversity, population movements, and admixtures of high-altitude East Asians via comprehensive population genetic statistical tools [principal component analysis (PCA), multidimensional scaling plot (MDS), STRUCTURE/ADMIXTURE, f3, f4, qpWave/qpAdm, and qpGraph]. Besides, we also explored their forensic characteristics and extended the Chinese National Database based on STR data. We identified 231 alleles with the corresponding allele frequencies spanning from 0.0005 to 0.5624 in the forensic low-density dataset, in which the combined powers of discrimination and the probability of exclusion were 1–1.22E-24 and 0.999999998, respectively. Additionally, comprehensive population comparisons in our low-density data among 57 worldwide populations via the Nei’s genetic distance, PCA, MDS, NJ tree, and STRUCTURE analysis indicated that the highland Tibeto-Burman speakers kept the close genetic relationship with ethnically close populations. Findings from the 1240K high-density dataset not only confirmed the close genetic connection between modern Highlanders, Nepal ancients (Samdzong, Mebrak, and Chokhopani), and the upper Yellow River Qijia people, suggesting the northeastern edge of the TP served as a geographical corridor for ancient population migrations and interactions between highland and lowland regions, but also evidenced that late Neolithic farmers permanently colonized into the TP by adopting cold-tolerant barley agriculture that was mediated via the acculturation of idea via the millet farmer and not via the movement of barley agriculturalist as no obvious western Eurasian admixture signals were identified in our analyzed modern and ancient populations. Besides, results from the qpAdm-based admixture proportion estimation and qpGraph-based phylogenetic relationship reconstruction consistently demonstrated that all ancient and modern highland East Asians harbored and shared the deeply diverged Onge/Hoabinhian-related eastern Eurasian lineage, suggesting a common Paleolithic genetic legacy existed in high-altitude East Asians as the first layer of their gene pool.

Genomic history and forensic characteristics of Sherpa highlanders on the Tibetan Plateau inferred from high-resolution genome-wide InDels and SNPs

“…Genetic similarity and continuity between the Sherpas and ancient populations and Tibetan groups on the Tibetan Plateau were further confirmed by their excess shared alleles revealed in f-statistics, qpWave/qpAdm-based admixture models, and qpGraph-based evolutionary topology. Moreover, we found that Lajia_LN-related ancestry contributed the most to the gene pool of modern Sherpa and Tibetan populations, suggesting that Neolithic millet farmers played a pivotal role in the formation of modern Sherpas and Tibetans, which was consistent with previous genetic findings [36,53,59]. The haplotype-based genetic observations further confirmed the recent common ancestor sharing between the Sherpas and Tibetans.…”

“…The previous genetic analyses focused on the peopling of Tibetan Plateau mainly based on allele-based sharing ancestry or only modern genomes without the comprehensively comparative analysis based on both modern and ancient references [9, 57,58]. Our recent population genetic analyses have started to directly explore the direct genetic contribution from ancient East Asians to modern Tibetan Plateau Tibetans based on ancient genomes, but the genetic history of Sherpa people and their forensic characteristics still need to be further studied [59][60][61]. In the present study, we first performed an InDel-based forensic and population genetic study to explore the genetic relatedness between Sherpa highlanders and worldwide reference populations.…”

Fine-Scale Genetic Structure and Natural Selection Signatures of Southwestern Hans Inferred From Patterns of Genome-Wide Allele, Haplotype, and Haplogroup Lineages

“…Southwestern East Asia is one of the most ethnolinguistically diverse regions around the world. Genetic origin, subsequent migration, isolation, plausible admixture, and local adaptation history of ethnolinguistic southern Chinese populations were widely discussed via different genetic markers, mainly including autosomal short tandem repeats (STRs), single nucleotide polymorphism (SNPs), and copy number variations (CNVs) ( Chen et al, 2019 ; Zhang C. et al, 2019 ; He et al, 2021 ; Liu et al, 2021a ). However, most of these studies focused on the genetic variations and forensic features of low-density genetic markers in the Han Chinese populations.…”

Genomic Insight Into the Population Admixture History of Tungusic-Speaking Manchu People in Northeast China

“…The genetic distances between the Manchus and the Altaic language-speaking populations such as Hezhen, Daur, and Oroqen were smaller than those of other language-speaking populations ( Zhao et al, 2011 ; Liu et al, 2013 ; Xing et al, 2019 ). Most genetic investigations based on the high-density genome-wide genetic variations from non-Altaic people in East Asia have revealed a fine-scale genetic landscape of genetic diversity and population admixture among the populations from different-language families ( He et al, 2021a , c ; Liu et al, 2021a , b ; Wang et al, 2021d ; Yao et al, 2021 ). Besides, recent genome-wide studies among Altaic-speaking populations in Northeast Asia have also found differentiated genetic admixture profiles between northern and southern Altaic-speaking populations and eastern and western Mongolians ( He et al, 2021b ).…”