title: Ancestral Origins and Genetic History of Tibetan Highlanders.
abstract: The origin of Tibetans remains one of the most contentious puzzles in history, anthropology, and genetics. Analyses of deeply sequenced (30×-60×) genomes of 38 Tibetan highlanders and 39 Han Chinese lowlanders, together with available data on archaic and modern humans, allow us to comprehensively characterize the ancestral makeup of Tibetans and uncover their origins. Non-modern human sequences compose ∼6% of the Tibetan gene pool and form unique haplotypes in some genomic regions, where Denisovan-like, Neanderthal-like, ancient-Siberian-like, and unknown ancestries are entangled and elevated. The shared ancestry of Tibetan-enriched sequences dates back to ∼62,000-38,000 years ago, predating the Last Glacial Maximum (LGM) and representing early colonization of the plateau. Nonetheless, most of the Tibetan gene pool is of modern human origin and diverged from that of Han Chinese ∼15,000 to ∼9,000 years ago, which can be largely attributed to post-LGM arrivals. Analysis of ∼200 contemporary populations showed that Tibetans share ancestry with populations from East Asia (∼82%), Central Asia and Siberia (∼11%), South Asia (∼6%), and western Eurasia and Oceania (∼1%). Our results support that Tibetans arose from a mixture of multiple ancestral gene pools but that their origins are much more complicated and ancient than previously suspected. We provide compelling evidence of the co-existence of Paleolithic and Neolithic ancestries in the Tibetan gene pool, indicating a genetic continuity between pre-historical highland-foragers and present-day Tibetans. In particular, highly differentiated sequences harbored in highlanders' genomes were most likely inherited from pre-LGM settlers of multiple ancestral origins (SUNDer) and maintained in high frequency by natural selection.
authors: Key Laboratory of Computational Biology, Max Planck Independent Research Group on Population Genomics, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors: Dongsheng
authors: D
authors: Lu
authors: Key Laboratory of Computational Biology, Max Planck Independent Research Group on Population Genomics, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors: Haiyi
authors: H
authors: Lou
authors: Key Laboratory of Computational Biology, Max Planck Independent Research Group on Population Genomics, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors: Kai
authors: K
authors: Yuan
authors: Key Laboratory of Computational Biology, Max Planck Independent Research Group on Population Genomics, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 200031, China.
authors: Xiaoji
authors: X
authors: Wang
authors: Key Laboratory of Computational Biology, Max Planck Independent Research Group on Population Genomics, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors: Yuchen
authors: Y
authors: Wang
authors: Key Laboratory of Computational Biology, Max Planck Independent Research Group on Population Genomics, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors: Chao
authors: C
authors: Zhang
authors: Key Laboratory of Computational Biology, Max Planck Independent Research Group on Population Genomics, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors: Yan
authors: Y
authors: Lu
authors: Key Laboratory of Computational Biology, Max Planck Independent Research Group on Population Genomics, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors: Xiong
authors: X
authors: Yang
authors: Key Laboratory of Computational Biology, Max Planck Independent Research Group on Population Genomics, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors: Lian
authors: L
authors: Deng
authors: Key Laboratory of Computational Biology, Max Planck Independent Research Group on Population Genomics, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors: Ying
authors: Y
authors: Zhou
authors: Key Laboratory of Computational Biology, Max Planck Independent Research Group on Population Genomics, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors: Qidi
authors: Q
authors: Feng
authors: State Key Laboratory of Genetic Engineering and Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai 200433, China.
authors: Ya
authors: Y
authors: Hu
authors: State Key Laboratory of Genetic Engineering and Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai 200433, China.
authors: Qiliang
authors: Q
authors: Ding
authors: State Key Laboratory of Genetic Engineering and Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai 200433, China.
authors: Yajun
authors: Y
authors: Yang
authors: State Key Laboratory of Genetic Engineering and Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai 200433, China.
authors: Shilin
authors: S
authors: Li
authors: State Key Laboratory of Genetic Engineering and Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai 200433, China.
authors: Li
authors: L
authors: Jin
authors: Department of Biochemistry and Molecular Biology, Preclinical Medicine College, Xinjiang Medical University, Urumqi 830011, China.
authors: Yaqun
authors: Y
authors: Guan
authors: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.
authors: Bing
authors: B
authors: Su
authors: Key Laboratory for Molecular Genetic Mechanisms and Intervention Research on High Altitude Disease of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang Shaanxi 712082, China.
authors: Longli
authors: L
authors: Kang
authors: Key Laboratory of Computational Biology, Max Planck Independent Research Group on Population Genomics, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 200031, China; Collaborative Innovation Center of Genetics and Development, Shanghai 200438, China. Electronic address: xushua@picb.ac.cn.
authors: Shuhua
authors: S
authors: Xu
mesh_terms: D000531:Altitude; D000818:Animals; D044466:Asian People / Q000235:genetics*; D002681:China / Q000208:ethnology; D005006:Ethnicity / Q000235:genetics; D051456:Gene Flow / Q000235:genetics*; D005788:Gene Pool; D005828:Genetics, Population; D015894:Genome, Human / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008957:Models, Genetic; D059125:Neanderthals / Q000235:genetics; D044349:Oceania / Q000208:ethnology; D010802:Phylogeny; D012641:Selection, Genetic; D018609:Tibet
keywords: Denisovan; Neanderthal; Sherpa; Tibetan; archaic ancestry; genetic history; next-generation sequencing