bioRxiv Science⌕ Search

bioRxiv · 10.1101/2020.07.03.185884

Peopling of Tibet Plateau and multiple waves of admixture of Tibetans inferred from both modern and ancient genome-wide data

Abstract

Archeologically attested human occupation on the Tibet Plateau (TP) can be traced back to 160 thousand years ago (kya, Xiahe) via archaic people and 30~40 kya via anatomically modern human in Nwya Devu. However, the past human movements and peopling of the TP keep in its infancy in the modern/ancient DNA studies. Here, we performed the first modern/ancient genomic meta-analysis among 3,017 Paleolithic to present-day eastern Eurasian genomes (2,444 modern individuals from 183 populations (including 98 Ü-Tsang/Ando/Kham Tibetans) and 573 ancients (including 161 Chinese ancients first meta-analyzed here)). Closer genetic connection between ancient-modern highland Tibetans and lowland island/coastal Neolithic northern East Asians was identified, reflecting the main ancestry of high-altitude Tibeto-Burman speakers originated from the ancestors of Houli/Yangshao/Longshan ancients in the middle and lower Yellow River basin, consistent with the common North-China origin of Sino-Tibetan language and dispersal pattern of millet farmers. Although the shared common northern East Asian lineage between Tibetans and lowland East Asians, we still identified genetic differentiation between Highlanders and lowland northern East Asians, the former harboring more deeply diverged Hoabinhian/Onge ancestry and the latter possessing more modern Neolithic southern East Asian and Siberian ancestry, which suggested the co-existence of Paleolithic and Neolithic ancestries in modern and Neolithic East Asian Highlanders. Tibetans from Ü-Tsang/Ando/Kham Tibetan regions showed strong population stratifications consistent with their cultural backgrounds and geographic terrains (showed as barriers for human movements): stronger Chokhopani affinity in Ü-Tsang Tibetans, more western Eurasian ancestry in Ando and greater Neolithic southern East Asian ancestry in Kham Tibetan. Modern combined ancient genomes documented multiple waves of human migrations in TP past: the first layer of local Hunter-Gatherer mixed with Qijia Farmer arose the Chokhopani-associated Proto-Tibetan-Burman, admixture with the additional genetic materials from the western Eurasian steppe, Yellow River and Yangtze River respectively gave rise to modern Ando, Ü-Tsang and Kham Tibetans.Competing Interest StatementThe authors have declared no competing interest.View Full Text

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Wang, M., Zou, X., Ye, H.-Y., Liu, Y., Wang, Z., Liu, J., Yao, H., Chen, P., Wang, F., Tao, R., Wang, S., Wei, L.-H., Tang, R., Wang, C.-C., He, G.. 2020-07-03. Peopling of Tibet Plateau and multiple waves of admixture of Tibetans inferred from both modern and ancient genome-wide data. https://doi.org/10.1101/2020.07.03.185884

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

Pangenome Discoveries from Clinical Long-Read Genomes in Underrepresented Populations with Neurodevelopmental Disorders

Genetic diagnoses remain elusive for many individuals with neurodevelopmental disorders (NDDs), and the gap is wider in populations poorly represented in genomic reference resources. To demonstrate the equitable advantage of long-read whole genome sequencing (LR-WGS) and pangenomes in terms of clinical utility, we analyzed 211 NDD cases and 107 unaffected relatives from 24 populations, integrating their assemblies, resulting in a total of 1204 haplotypes with the Human Pangenome Reference Consortium Release 2 (HPRC_r2) and the Arab Pangenome Reference (APR) datasets. Clinical interpretation of small variants and structural variants (SVs) revealed pathogenic or likely pathogenic findings in 38.9% of the cases (82/211), and our workflow further detected pathogenic repeat expansions in 3.8% of the cases and runs of homozygosity (ROHs) exceeding 300 Mb in 4.7% of the cases, revealing substantial autozygosity suggestive of strong inbreeding. Beyond these clinical assessments, pangenome analysis revealed 3.9 million population-level novel small variants, 39,782 SVs and an average of 2.17 Mb of novel sequence per individual absent from linear references and global pangenomes. We identified 85.9 kb of case-unique nonreference sequences in exonic segments overlapping with curated NDD gene sets. Graph-based tertiary analysis further identified rare exonic complex homozygous rearrangements in the NDD associated genes for 2.4% of the cases. Together, these findings emphasize how diverse genome assemblies extend variant discovery beyond established linear reference-based clinical interpretation.

genetics↗

Integrated exome-transcriptome analysis of a schizophrenia case with an exceptionally low polygenic risk score

Schizophrenia liability reflects both common polygenic variation and rarer variants of larger effect. We investigated a post-mortem schizophrenia case (SZ07) with a schizophrenia polygenic risk score below the first percentile among ancestry-matched cases, asking whether individual-level genomic and transcriptomic analyses could help identify potentially novel schizophrenia-relevant variants. We used exome analysis with multiple variant-prediction tools to generate a panel of variants and corresponding candidate genes potentially implicated in the pathological process in SZ07. The prioritised variants were then assessed using RNA sequencing of three cortical regions. Of these, only an IZUMO4 splice-acceptor variant showed direct RNA-level support. Beyond variant-specific analyses, we characterised broader transcriptomic abnormalities in the SZ07 brain. Pathway analysis of gene-level expression deviations implicated innate immune processes, calcium signalling, synaptic biology, and axon remodelling. Notably, compared with conventional single-sample biological pathway analysis, the analysis we used showed only a weak association with neuronal specificity, suggesting their reduced sensitivity to the main axis of variation related to cellular composition in bulk brain tissue gene expression data. Although the candidate genes showed no significant pathway-level convergence, the broader transcriptomic profile revealed coherent biological alterations largely compatible with the documented history of cerebrovascular disease in SZ07. These results demonstrate how the integration of exome and transcriptome data at the individual level enables the formulation and constraint of hypotheses regarding patient-specific genetic features and their molecular consequences, while highlighting important limitations related to tissue composition, comorbidity, and the choice of reference cohort.

genetics↗

A genetic screen to identify host factors required for commensal bacterial adherence to the gut epithelia

Bacterial adherence to gut epithelial cells likely involves host genetic components. We isolated a gut commensal bacterium, Lelliottia jeotgali, that can robustly colonize C. elegans through attachment to intestinal epithelial cells. Here, we developed a novel screen in C. elegans to identify host genes required for microbiome bacterial colonization. Using transgenic L. jeotgali strain expressing tdTomato, we conducted forward genetic screens in C. elegans to select for mutants that completely lost colonization. We identified multiple allelic mutations in five different C. elegans genes, termed knockout of Lelliottia adherence (kola) mutants, with a near complete loss of adherence. Each of kola-1-5 is uncharacterized and predicted to encode for a secreted or membrane-bound protein. We also identified gly-5, a GalNAc transferase that initiates O-linked glycosylation. Overall, we describe the first C. elegans screen to identify host factors that control microbiome bacterial colonization in the gut.

genetics↗