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On the origin of Tibetans and their genetic basis in adapting high-altitude environments.

Wang B, Zhang YB, Zhang F, Lin H, Wang X, Wan N, Ye Z, Weng H, Zhang L, Li X, Yan J, Wang P, Wu T, Cheng L, Wang J, Wang DM, Ma X, Yu J - PLoS ONE (2011)

Bottom Line: Since their arrival in the Tibetan Plateau during the Neolithic Age, Tibetans have been well-adapted to extreme environmental conditions and possess genetic variation that reflect their living environment and migratory history.Our findings suggested that Tibetans, together with the Yi people, were descendants of Tibeto-Burmans who diverged from ancient settlers of East Asia.The valleys of the Hengduan Mountain range may be a major migration route.

View Article: PubMed Central - PubMed

Affiliation: National Research Institute for Family Planning, Beijing, People's Republic of China.

ABSTRACT
Since their arrival in the Tibetan Plateau during the Neolithic Age, Tibetans have been well-adapted to extreme environmental conditions and possess genetic variation that reflect their living environment and migratory history. To investigate the origin of Tibetans and the genetic basis of adaptation in a rigorous environment, we genotyped 30 Tibetan individuals with more than one million SNP markers. Our findings suggested that Tibetans, together with the Yi people, were descendants of Tibeto-Burmans who diverged from ancient settlers of East Asia. The valleys of the Hengduan Mountain range may be a major migration route. We also identified a set of positively-selected genes that belong to functional classes of the embryonic, female gonad, and blood vessel developments, as well as response to hypoxia. Most of these genes were highly correlated with population-specific and beneficial phenotypes, such as high infant survival rate and the absence of chronic mountain sickness.

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Related in: MedlinePlus

Significant genomic regions indentified in Tibetans by iHS, XP-EHH, and FST.Ten selection tests (one iHS, two XP-EHH, and seven FST, showed as columns) were performed on Tibetans or Tibetan-included pairs, and empirical P-value of each 200-kb genomic window (showed as row) was obtained. Windows with P≤0.02 are listed, and then sorted according to the numbers of significant appearances. Only windows that appeared at least four times are shown. The physical position of each window on the human genome is labeled on the left of plot. Genes within or near each window are shown on the right. Genes without functional summary provided by RefSeq were removed. The windows with no functional genes are not shown.
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pone-0017002-g002: Significant genomic regions indentified in Tibetans by iHS, XP-EHH, and FST.Ten selection tests (one iHS, two XP-EHH, and seven FST, showed as columns) were performed on Tibetans or Tibetan-included pairs, and empirical P-value of each 200-kb genomic window (showed as row) was obtained. Windows with P≤0.02 are listed, and then sorted according to the numbers of significant appearances. Only windows that appeared at least four times are shown. The physical position of each window on the human genome is labeled on the left of plot. Genes within or near each window are shown on the right. Genes without functional summary provided by RefSeq were removed. The windows with no functional genes are not shown.

Mentions: Since genetic loci under positive selection may not always give rise to extremely high FST [19], we also used two haplotype-based methods, iHS (integrated Haplotype Score) and XP-EHH (Cross Population Extended Haplotype Homozygosity) to detect significant reductions in gene diversity around selected loci [21], [22], [23]. The most significant region (P<0.008 in all tests) was located on chromosome 2 from 46.4 Mb to 46.6 Mb; both of its adjacent 200-kb regions also showed significant values (Figure 2). This suggests that strong selection and the near-complete selective sweeps have occurred in this genomic region. To uncover the potential causal genes, we plotted the FST values of SNPs in a 6-Mb region flanking the site of interest, for FST signals normally peak around the causal variant [24]. In Figure 3, the FST signals peak at EPAS1, a critical hypoxia inducible factor, in all Tibetan pairs. For population pairs from other East Asian (including Yi), no peaks were observed at EPAS1. This suggests that EPAS1 is potentially under positive selection only in Tibetans. The second significant region (P<0.02 in 6 tests) also show near-complete sweep to the surrounding 600-kb area. The EGLN1 gene within this region is also involved in the response to hypoxia and potentially be the target of positive selection. EPAS1 and EGLN1 play central roles in the activation of hypoxia-inducible genes and homeostasis of HIF under hypoxia and normoxia [25], [26]. Other genomic regions yielded significant test statistics for selected genes, including CDH13, ANGPT1, RUNX1, FOXO1, JMJD2C, GLIS3, MAT2B, A2M, RYR1, and NPAS3 (Figure 2).


On the origin of Tibetans and their genetic basis in adapting high-altitude environments.

Wang B, Zhang YB, Zhang F, Lin H, Wang X, Wan N, Ye Z, Weng H, Zhang L, Li X, Yan J, Wang P, Wu T, Cheng L, Wang J, Wang DM, Ma X, Yu J - PLoS ONE (2011)

Significant genomic regions indentified in Tibetans by iHS, XP-EHH, and FST.Ten selection tests (one iHS, two XP-EHH, and seven FST, showed as columns) were performed on Tibetans or Tibetan-included pairs, and empirical P-value of each 200-kb genomic window (showed as row) was obtained. Windows with P≤0.02 are listed, and then sorted according to the numbers of significant appearances. Only windows that appeared at least four times are shown. The physical position of each window on the human genome is labeled on the left of plot. Genes within or near each window are shown on the right. Genes without functional summary provided by RefSeq were removed. The windows with no functional genes are not shown.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3046130&req=5

pone-0017002-g002: Significant genomic regions indentified in Tibetans by iHS, XP-EHH, and FST.Ten selection tests (one iHS, two XP-EHH, and seven FST, showed as columns) were performed on Tibetans or Tibetan-included pairs, and empirical P-value of each 200-kb genomic window (showed as row) was obtained. Windows with P≤0.02 are listed, and then sorted according to the numbers of significant appearances. Only windows that appeared at least four times are shown. The physical position of each window on the human genome is labeled on the left of plot. Genes within or near each window are shown on the right. Genes without functional summary provided by RefSeq were removed. The windows with no functional genes are not shown.
Mentions: Since genetic loci under positive selection may not always give rise to extremely high FST [19], we also used two haplotype-based methods, iHS (integrated Haplotype Score) and XP-EHH (Cross Population Extended Haplotype Homozygosity) to detect significant reductions in gene diversity around selected loci [21], [22], [23]. The most significant region (P<0.008 in all tests) was located on chromosome 2 from 46.4 Mb to 46.6 Mb; both of its adjacent 200-kb regions also showed significant values (Figure 2). This suggests that strong selection and the near-complete selective sweeps have occurred in this genomic region. To uncover the potential causal genes, we plotted the FST values of SNPs in a 6-Mb region flanking the site of interest, for FST signals normally peak around the causal variant [24]. In Figure 3, the FST signals peak at EPAS1, a critical hypoxia inducible factor, in all Tibetan pairs. For population pairs from other East Asian (including Yi), no peaks were observed at EPAS1. This suggests that EPAS1 is potentially under positive selection only in Tibetans. The second significant region (P<0.02 in 6 tests) also show near-complete sweep to the surrounding 600-kb area. The EGLN1 gene within this region is also involved in the response to hypoxia and potentially be the target of positive selection. EPAS1 and EGLN1 play central roles in the activation of hypoxia-inducible genes and homeostasis of HIF under hypoxia and normoxia [25], [26]. Other genomic regions yielded significant test statistics for selected genes, including CDH13, ANGPT1, RUNX1, FOXO1, JMJD2C, GLIS3, MAT2B, A2M, RYR1, and NPAS3 (Figure 2).

Bottom Line: Since their arrival in the Tibetan Plateau during the Neolithic Age, Tibetans have been well-adapted to extreme environmental conditions and possess genetic variation that reflect their living environment and migratory history.Our findings suggested that Tibetans, together with the Yi people, were descendants of Tibeto-Burmans who diverged from ancient settlers of East Asia.The valleys of the Hengduan Mountain range may be a major migration route.

View Article: PubMed Central - PubMed

Affiliation: National Research Institute for Family Planning, Beijing, People's Republic of China.

ABSTRACT
Since their arrival in the Tibetan Plateau during the Neolithic Age, Tibetans have been well-adapted to extreme environmental conditions and possess genetic variation that reflect their living environment and migratory history. To investigate the origin of Tibetans and the genetic basis of adaptation in a rigorous environment, we genotyped 30 Tibetan individuals with more than one million SNP markers. Our findings suggested that Tibetans, together with the Yi people, were descendants of Tibeto-Burmans who diverged from ancient settlers of East Asia. The valleys of the Hengduan Mountain range may be a major migration route. We also identified a set of positively-selected genes that belong to functional classes of the embryonic, female gonad, and blood vessel developments, as well as response to hypoxia. Most of these genes were highly correlated with population-specific and beneficial phenotypes, such as high infant survival rate and the absence of chronic mountain sickness.

Show MeSH
Related in: MedlinePlus