Xuebin Qi

Bio: Xuebin Qi is an academic researcher from Kunming Institute of Zoology. The author has contributed to research in topics: Population & Haplogroup. The author has an hindex of 22, co-authored 43 publications receiving 1685 citations. Previous affiliations of Xuebin Qi include Chinese Academy of Sciences & International Livestock Research Institute.

Genetic variations in Tibetan populations and high altitude adaptation at the Himalayas

Abstract: Modern humans have occupied almost all possible environments globally since exiting Africa about 100,000 years ago. Both behavioral and biological adaptations have contributed to their success in surviving the rigors of climatic extremes, including cold, strong ultraviolet radiation, and high altitude. Among these environmental stresses, high-altitude hypoxia is the only condition in which traditional technology is incapable of mediating its effects. Inhabiting at .3,000-m high plateau, the Tibetan population provides a widely studied example of high-altitude adaptation. Yet, the genetic mechanisms underpinning long-term survival in this environmental extreme remain unknown. We performed an analysis of genome-wide sequence variations in Tibetans. In combination with the reported data, we identified strong signals of selective sweep in two hypoxia-related genes, EPAS1 and EGLN1. For these two genes, Tibetans show unusually high divergence from the nonTibetan lowlanders (Han Chinese and Japanese) and possess high frequencies of many linked sequence variations as reflected by the Tibetan-specific haplotypes. Further analysis in seven Tibetan populations (1,334 individuals) indicates the prevalence of selective sweep across the Himalayan region. The observed indicators of natural selection on EPAS1 and EGLN1 suggest that during the long-term occupation of high-altitude areas, the functional sequence variations for acquiring biological adaptation to high-altitude hypoxia have been enriched in Tibetan populations.

Genetic Evidence of Paleolithic Colonization and Neolithic Expansion of Modern Humans on the Tibetan Plateau

Abstract: Tibetans live on the highest plateau in the world, their current population size is approximately 5 million, and most of them live at an altitude exceeding 3,500 m. Therefore, the Tibetan Plateau is a remarkable area for cultural and biological studies of human population history. However, the chronological profile of the Tibetan Plateau's colonization remains an unsolved question of human prehistory. To reconstruct the prehistoric colonization and demographic history of modern humans on the Tibetan Plateau, we systematically sampled 6,109 Tibetan individuals from 41 geographic populations across the entire region of the Tibetan Plateau and analyzed the phylogeographic patterns of both paternal (n = 2,354) and maternal (n = 6,109) lineages as well as genome-wide single nucleotide polymorphism markers (n = 50) in Tibetan populations. We found that there have been two distinct, major prehistoric migrations of modern humans into the Tibetan Plateau. The first migration was marked by ancient Tibetan genetic signatures dated to approximately 30,000 years ago, indicating that the initial peopling of the Tibetan Plateau by modern humans occurred during the Upper Paleolithic rather than Neolithic. We also found evidences for relatively young (only 7-10 thousand years old) shared Y chromosome and mitochondrial DNA haplotypes between Tibetans and Han Chinese, suggesting a second wave of migration during the early Neolithic. Collectively, the genetic data indicate that Tibetans have been adapted to a high altitude environment since initial colonization of the Tibetan Plateau in the early Upper Paleolithic, before the last glacial maximum, followed by a rapid population expansion that coincided with the establishment of farming and yak pastoralism on the Plateau in the early Neolithic.

Y chromosome evidence of earliest modern human settlement in East Asia and multiple origins of Tibetan and Japanese populations

Abstract: The phylogeography of the Y chromosome in Asia previously suggested that modern humans of African origin initially settled in mainland southern East Asia, and about 25,000–30,000 years ago, migrated northward, spreading throughout East Asia. However, the fragmented distribution of one East Asian specific Y chromosome lineage (D-M174), which is found at high frequencies only in Tibet, Japan and the Andaman Islands, is inconsistent with this scenario. In this study, we collected more than 5,000 male samples from 73 East Asian populations and reconstructed the phylogeography of the D-M174 lineage. Our results suggest that D-M174 represents an extremely ancient lineage of modern humans in East Asia, and a deep divergence was observed between northern and southern populations. We proposed that D-M174 has a southern origin and its northward expansion occurred about 60,000 years ago, predating the northward migration of other major East Asian lineages. The Neolithic expansion of Han culture and the last glacial maximum are likely the key factors leading to the current relic distribution of D-M174 in East Asia. The Tibetan and Japanese populations are the admixture of two ancient populations represented by two major East Asian specific Y chromosome lineages, the O and D haplogroups.

Identification of a Tibetan-specific mutation in the hypoxic gene EGLN1 and its contribution to high-altitude adaptation

Abstract: Tibetans are well adapted to high-altitude hypoxic conditions, and in recent genome-wide scans, many candidate genes have been reported involved in the physiological response to hypoxic conditions. However, the limited sequence variations analyzed in previous studies would not be sufficient to identify causal mutations. Here we conducted resequencing of the entire genomic region (59.4kb) of the hypoxic geneEGLN1(one of the top candidates from the genome-wide scans) in Tibetans and identified 185 sequence variations, including 13 novel variations (12 substitutions and 1 insertion or deletion). There is a nonsynonymous mutation (rs186996510, D4E) showing surprisingly deep divergence between Tibetans and lowlander populations (FST=0.709 between Tibetans and Han Chinese). It is highly prevalent in Tibetans (70.9% on average) but extremely rare in Han Chinese, Japanese, Europeans, and Africans (0.56‐2.27%), suggesting that it might be the causal mutation of EGLN1 contributing to high-altitude hypoxic adaptation. Neutrality test confirmed the signal of Darwinian positive selection on EGLN1 in Tibetans. Haplotype network analysis revealed a Tibetan-specific haplotype, which is absent in other world populations. The estimated selective intensity (0.029 for the C allele of rs186996510) puts EGLN1 among the known genes that have undergone the strongest selection in human populations, and the onset of selection was estimated to have started at the early Neolithic (~8,400 years ago). Finally, we detected a significant association between rs186996510 and hemoglobin levels in Tibetans, suggesting that EGLN1 contributes to the adaptively low hemoglobin level of Tibetans compared with acclimatized lowlanders at high altitude.

Extended Y Chromosome Investigation Suggests Postglacial Migrations of Modern Humans into East Asia via the Northern Route

Abstract: Genetic diversity data, from Y chromosome and mitochondrial DNA as well as recent genome-wide autosomal single nucleotide polymorphisms, suggested that mainland Southeast Asia was the major geographic source of East Asian populations. However, these studies also detected Central–South Asia (CSA)- and/or West Eurasia (WE)-related genetic components in East Asia, implying either recent population admixture or ancient migrations via the proposed northern route. To trace the time period and geographic source of these CSA- and WE-related genetic components, we sampled 3,826 males (116 populations from China and 1 population from North Korea) and performed high-resolution genotyping according to the well-resolved Y chromosome phylogeny. Our data, in combination with the published East Asian Yhaplogroup data, show that there are four dominant haplogroups (accounting for 92.87% of the East Asian Y chromosomes), O-M175, D-M174, C-M130 (not including C5-M356), and N-M231, in both southern and northern East Asian populations, which is consistent with the proposed southern route of modern human origin in East Asia. However, there are other haplogroups (6.79% in total) (E-SRY4064, C5-M356, G-M201, H-M69, I-M170, J-P209, L-M20, Q-M242, R-M207, and T-M70) detected primarily in northern East Asian populations and were identified as Central-South Asian and/or West Eurasian origin based on the phylogeographic analysis. In particular, evidence of geographic distribution and Y chromosome short tandem repeat (Y-STR) diversity indicates that haplogroup Q-M242 (the ancestral haplogroup of the native American-specific haplogroup Q1a3a-M3) and R-M207 probably migrated into East Asia via the northern route. The age estimation of Y-STR variation within haplogroups suggests the existence of postglacial (;18 Ka) migrations via the northern route as well as recent (;3 Ka) population admixture. We propose that although the Paleolithic migrations via the southern route played a major role in modern human settlement in East Asia, there are ancient contributions, though limited, from WE, which partly explain the genetic divergence between current southern and northern East Asian populations.

Integrative analysis of 111 reference human epigenomes

Abstract: The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.

Ancient human genomes suggest three ancestral populations for present-day Europeans

Abstract: We sequenced the genomes of a ∼7,000-year-old farmer from Germany and eight ∼8,000-year-old hunter-gatherers from Luxembourg and Sweden. We analysed these and other ancient genomes with 2,345 contemporary humans to show that most present-day Europeans derive from at least three highly differentiated populations: west European hunter-gatherers, who contributed ancestry to all Europeans but not to Near Easterners; ancient north Eurasians related to Upper Palaeolithic Siberians, who contributed to both Europeans and Near Easterners; and early European farmers, who were mainly of Near Eastern origin but also harboured west European hunter-gatherer related ancestry. We model these populations' deep relationships and show that early European farmers had ∼44% ancestry from a 'basal Eurasian' population that split before the diversification of other non-African lineages.

Altitude adaptation in Tibetans caused by introgression of Denisovan-like DNA

Abstract: As modern humans migrated out of Africa, they encountered many new environmental conditions, including greater temperature extremes, different pathogens and higher altitudes. These diverse environments are likely to have acted as agents of natural selection and to have led to local adaptations. One of the most celebrated examples in humans is the adaptation of Tibetans to the hypoxic environment of the high-altitude Tibetan plateau. A hypoxia pathway gene, EPAS1, was previously identified as having the most extreme signature of positive selection in Tibetans, and was shown to be associated with differences in haemoglobin concentration at high altitude. Re-sequencing the region around EPAS1 in 40 Tibetan and 40 Han individuals, we find that this gene has a highly unusual haplotype structure that can only be convincingly explained by introgression of DNA from Denisovan or Denisovan-related individuals into humans. Scanning a larger set of worldwide populations, we find that the selected haplotype is only found in Denisovans and in Tibetans, and at very low frequency among Han Chinese. Furthermore, the length of the haplotype, and the fact that it is not found in any other populations, makes it unlikely that the haplotype sharing between Tibetans and Denisovans was caused by incomplete ancestral lineage sorting rather than introgression. Our findings illustrate that admixture with other hominin species has provided genetic variation that helped humans to adapt to new environments.