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Present-day Tibetans have adapted both genetically and culturally to the high altitude environment of the Tibetan Plateau, but fundamental questions about their origins remain unanswered. Recent archaeological and genetic research suggests the presence of an early population on the Plateau within the past 40 thousand years, followed by the arrival of subsequent groups within the past 10 thousand years. Here, we obtain new genome-wide data for 33 ancient individuals from high elevation sites on the southern fringe of the Tibetan Plateau in Nepal, who we show are most closely related to present-day Tibetans. They derive most of their ancestry from groups related to Late Neolithic populations at the northeastern edge of the Tibetan Plateau but also harbor a minor genetic component from a distinct and deep Paleolithic Eurasian ancestry. In contrast to their Tibetan neighbors, present-day non-Tibetan Tibeto-Burman speakers living at mid-elevations along the southern and eastern margins of the Plateau form a genetic cline that reflects a distinct genetic history. Finally, a comparison between ancient and present-day highlanders confirms ongoing positive selection of high altitude adaptive alleles. Liu et al. report genome-wide data of 33 ancient individuals from the Himalayas, illuminating the deep genetic history of Tibetans and other Tibeto-Burman-speaking populations around the Tibetan Plateau in fine resolution. [ABSTRACT FROM AUTHOR]

Adaptive evolution in humans has rarely been characterized for its whole set of components, i.e. selective pressure, adaptive phenotype, beneficial alleles and realized fitness differential. We combined approaches for detecting polygenic adaptations and for mapping the genetic bases of physiological and fertility phenotypes in approximately 1000 indigenous ethnically Tibetan women from Nepal, adapted to high altitude. The results of genome-wide association analyses and tests for polygenic adaptations showed evidence of positive selection for alleles associated with more pregnancies and live births and evidence of negative selection for those associated with higher offspring mortality. Lower hemoglobin level did not show clear evidence for polygenic adaptation, despite its strong association with an EPAS1 haplotype carrying selective sweep signals. [ABSTRACT FROM AUTHOR]

The article presents a study on fractal and linear heart rate dynamics during sleep and at high altitudes. It states that the study involves electrocardiogram (ECG) monitoring of subjects at high altitude levels in Mount Everest. Results show that cardiac response during sleep at high altitudes can hardly be explored through heart rate variability (HRV) estimation. It also suggests supporting results with more sophisticated fractal and nonlinear cardiac variability features.

We chose the "natural laboratory" provided by high-altitude native ethnic Tibetan women who had completed childbearing to examine the hypothesis that multiple oxygen delivery traits were associated with lifetime reproductive success and had genomic associations. Four hundred seventeen (417) women aged 46 to 86 y residing at ≥3,500 m in Upper Mustang, Nepal, provided information on reproductive histories, sociocultural factors, physiological measurements, and DNA samples for this observational cohort study. Simultaneously assessing multiple traits identified combinations associated with lifetime reproductive success measured as the number of livebirths. Women with the most livebirths had distinctive hematological and cardiovascular traits. A hemoglobin concentration near the sample mode and a high percent of oxygen saturation of hemoglobin raised arterial oxygen concentration without risking elevated blood viscosity. We propose ongoing stabilizing selection on hemoglobin concentration because extreme values predicted fewer livebirths and directional selection favoring higher oxygen saturation because higher values had more predicted livebirths. EPAS1, an oxygen homeostasis locus with strong signals of positive natural selection and a high frequency of variants occurring only among populations indigenous to the Tibetan Plateau, associated with hemoglobin concentration. High blood flow into the lungs, wide left ventricles, and low hypoxic heart rate responses aided effective convective oxygen transport to tissues. Women with physiologies closer to unstressed, low altitude values had the highest lifetime reproductive success. This example of ethnic Tibetan women residing at high altitudes in Nepal links reproductive fitness with trait combinations increasing oxygen delivery under severe hypoxic stress and demonstrates ongoing natural selection., Competing Interests: Competing interests statement:The authors declare no competing interest.

While much research attention has focused on demographic processes that enabled human diffusion on the Tibetan plateau, little is known about more recent colonization of Southern Himalayas. In particular, the history of migrations, admixture and/or isolation of populations speaking Tibeto-Burman languages, which is supposed to be quite complex and to have reshaped patterns of genetic variation on both sides of the Himalayan arc, remains only partially elucidated. We thus described the genomic landscape of previously unsurveyed Tibeto-Burman (i.e. Sherpa and Tamang) and Indo-Aryan communities from remote Nepalese valleys. Exploration of their genomic relationships with South/East Asian populations provided evidence for Tibetan admixture with low-altitude East Asians and for Sherpa isolation. We also showed that the other Southern Himalayan Tibeto-Burmans derived East Asian ancestry not from the Tibetan/Sherpa lineage, but from low-altitude ancestors who migrated from China plausibly across Northern India/Myanmar, having experienced extensive admixture that reshuffled the ancestral Tibeto-Burman gene pool. These findings improved the understanding of the impact of gene flow/drift on the evolution of high-altitude Himalayan peoples and shed light on migration events that drove colonization of the southern Himalayan slopes, as well as on the role played by different Tibeto-Burman groups in such a complex demographic scenario.

Background: We set out to describe the fine-scale population structure across the Eastern region of Nepal. To date there is relatively little known about the genetic structure of the Sherpa residing in Nepal and their genetic relationship with the Nepalese. We assembled dense genotype data from a total of 1245 individuals representing Nepal and a variety of different populations resident across the greater Himalayan region including Tibet, China, India, Pakistan, Kazakhstan, Uzbekistan, Tajikistan and Kirghizstan. We performed analysis of principal components, admixture and homozygosity., Results: We identified clear substructure across populations resident in the Himalayan arc, with genetic structure broadly mirroring geographical features of the region. Ethnic subgroups within Nepal show distinct genetic structure, on both admixture and principal component analysis. We detected differential proportions of ancestry from northern Himalayan populations across Nepalese subgroups, with the Nepalese Rai, Magar and Tamang carrying the greatest proportions of Tibetan ancestry., Conclusions: We show that populations dwelling on the Himalayan plateau have had a clear impact on the Northern Indian gene pool. We illustrate how the Sherpa are a remarkably isolated population, with little gene flow from surrounding Nepalese populations.

We have previously reported that the Tharu people of the Terai region in southern Nepal have an incidence of malaria about sevenfold lower than that of synpatric non-Tharu people. In order to find out whether this marked resistance against malaria has a genetic basis, we have now determined in these populations the prevalence of candidate protective genes and have performed in-vitro cultures of Plasmodium falciparum in both Tharu and non-Tharu red cells. We have found significant but relatively low and variable frequencies of beta-thal, beta S, G6PD (-), and Duffy (a-b-) in different parts of the Terai region. The average in-vitro rate of invasion and of parasite multiplication did not differ significantly in red cells from Tharus versus those from non-Tharu controls. By contrast, the frequency of alpha-thalassemia is uniformly high in Tharus, with the majority of them having the homozygous alpha-/alpha-genotype and an overall alpha-thal gene (alpha-) frequency of .8. We suggest that holoendemic malaria has caused preferential survival of subjects with alpha-thal and that this genetic factor has enabled the Tharus as a population to survive for centuries in a malaria-holoendemic area. From our data we estimate that the alpha-thal homozygous state decreases morbidity from malaria by about 10-fold. This is an example of selection evolution toward fixation of an otherwise abnormal gene.