Project Publications

Jeong, C., Witonsky, D. B., Basnyat, B., Neupane, M., Beall, C. M., Childs, G., … & Di Rienzo, A. (2018). Detecting past and ongoing natural selection among ethnically Tibetan women at high altitude in Nepal. PLoS genetics, 14(9), e1007650. DOI. 

Abstract

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.

Cho, J. I., Basnyat, B., Jeong, C., Di Rienzo, A., Childs, G., Craig, S. R., … & Beall, C. M. (2017). Ethnically Tibetan women in Nepal with low hemoglobin concentration have better reproductive outcomes. Evolution, medicine, and public health, 2017(1), 82-96. DOI.

Abstract

Background and objectives: Tibetans have distinctively low hemoglobin concentrations at high altitudes compared with visitors and Andean highlanders. This study hypothesized that natural selection favors an unelevated hemoglobin concentration among Tibetans. It considered nonheritable sociocultural factors affecting reproductive success and tested the hypotheses that a higher percent of oxygen saturation of hemoglobin (indicating less stress) or lower hemoglobin concentration (indicating dampened response) associated with higher lifetime reproductive success.

Methodology: We sampled 1006 post-reproductive ethnically Tibetan women residing at 3000–4100 m in Nepal. We collected reproductive histories by interviews in native dialects and noninvasive physiological measurements. Regression analyses selected influential covariates of measures of reproductive success: the numbers of pregnancies, live births and children surviving to age 15.

Results: Taking factors such as marriage status, age of first birth and access to health care into account, we found a higher percent of oxygen saturation associated weakly and an unelevated hemoglobin concentration associated strongly with better reproductive success. Women who lost all their pregnancies or all their live births had hemoglobin concentrations significantly higher than the sample mean. Elevated hemoglobin concentration associated with a lower probability a pregnancy progressed to a live birth.

Conclusions and implications: These findings are consistent with the hypothesis that unelevated hemoglobin concentration is an adaptation shaped by natural selection resulting in the relatively low hemoglobin concentration of Tibetans compared with visitors and Andean highlanders.

Jeong, C., Peter, B. M., Basnyat, B., Neupane, M., Beall, C. M., Childs, G., … & Di Rienzo, A. (2017). A longitudinal cline characterizes the genetic structure of human populations in the Tibetan plateau. PLoS One, 12(4), e0175885. DOI.

Abstract

Indigenous populations of the Tibetan plateau have attracted much attention for their good performance at extreme high altitude. Most genetic studies of Tibetan adaptations have used genetic variation data at the genome scale, while genetic inferences about their demography and population structure are largely based on uniparental markers. To provide genome-wide information on population structure, we analyzed new and published data of 338 individuals from indigenous populations across the plateau in conjunction with worldwide genetic variation data. We found a clear signal of genetic stratification across the east-west axis within Tibetan samples. Samples from more eastern locations tend to have higher genetic affinity with lowland East Asians, which can be explained by more gene flow from lowland East Asia onto the plateau. Our findings corroborate a previous report of admixture signals in Tibetans, which were based on a subset of the samples analyzed here, but add evidence for isolation by distance in a broader geospatial context.

Craig, S. R., Childs, G., & Beall, C. M. (2016). Closing the womb door: contraception use and fertility transition among culturally Tibetan women in Highland Nepal. Maternal and child health journal, 20(12), 2437-2450. DOI.

Abstract

Objectives Whether in metropoles or remote mountain communities, the availability and adoption of contraceptive technologies prompt serious and wide-ranging biological, social, and political-economic questions. The potential shifts in women’s capacities to create spaces between pregnancies or to prevent future pregnancies have profound and often positive biological, demographic, and socioeconomic implications. Less acknowledged, however, are the ambivalences that women experience around contraception use—vacillations between moral frameworks, generational difference, and gendered forms of labor that have implications well beyond the boundaries of an individual’s reproductive biology. This paper hones in on contraceptive use of culturally Tibetan women in two regions of highland Nepal whose reproductive lives occurred from 1943 to 2012. Methods We describe the experiences of the 296 women (out of a study of more than 1000 women’s reproductive histories) who used contraception, and under what circumstances, examining socioeconomic, geographic, and age differences as well as points of access and patterns of use. We also provide a longitudinal perspective on fertility. Results Our results relate contraception usage to fertility decline, as well as to differences in access between the two communities of women. Conclusions We argue that despite seemingly similar social ecologies of these two study sites—including stated reasons for the adoption of contraception and expressed ambivalence around its use, some of which are linked to moral and cosmological understandings that emerge from Buddhism—the dynamics of contraception uptake in these two regions are distinct, as are, therefore, patterns of fertility transition.

Mallick, S., Li, H., Lipson, M., Mathieson, I., Gymrek, M., Racimo, F., … & Reich, D. (2016). The Simons genome diversity project: 300 genomes from 142 diverse populations. Nature, 538(7624), 201-206. DOI.

Abstract

Here we report the Simons Genome Diversity Project data set: high quality genomes from 300 individuals from 142 diverse populations. These genomes include at least 5.8 million base pairs that are not present in the human reference genome. Our analysis reveals key features of the landscape of human genome variation, including that the rate of accumulation of mutations has accelerated by about 5% in non-Africans compared to Africans since divergence. We show that the ancestors of some pairs of present-day human populations were substantially separated by 100,000 years ago, well before the archaeologically attested onset of behavioural modernity. We also demonstrate that indigenous Australians, New Guineans and Andamanese do not derive substantial ancestry from an early dispersal of modern humans; instead, their modern human ancestry is consistent with coming from the same source as that of other non-Africans.

Sudmant, P. H., Mallick, S., Nelson, B. J., Hormozdiari, F., Krumm, N., Huddleston, J., … & Eichler, E. E. (2015). Global diversity, population stratification, and selection of human copy-number variation. Science, 349(6253). DOI.

Abstract

In order to explore the diversity and selective signatures of duplication and deletion human copy-number variants (CNVs), we sequenced 236 individuals from 125 distinct human populations. We observed that duplications exhibit fundamentally different population genetic and selective signatures than deletions and are more likely to be stratified between human populations. Through reconstruction of the ancestral human genome, we identify megabases of DNA lost in different human lineages and pinpoint large duplications that introgressed from the extinct Denisova lineage now found at high frequency exclusively in Oceanic populations. We find that the proportion of CNV base pairs to single-nucleotide–variant base pairs is greater among non-Africans than it is among African populations, but we conclude that this difference is likely due to unique aspects of non-African population history as opposed to differences in CNV load.

Childs, G., Craig, S., Beall, C. M., & Basnyat, B. (2014). Depopulating the Himalayan highlands: Education and outmigration from ethnically Tibetan communities of Nepal. Mountain Research and Development, 34(2), 85-94. DOI. 

Abstract

Communities that have thrived for centuries in Nepal’s rugged mountain environments are facing rapid population declines caused by the outmigration of youths, both males and females in nearly equal numbers, who are sent by parents to distant boarding schools and monasteries for secular and religious education. This paper documents the magnitude of outmigration, migration destinations, migration’s impact on the age–sex composition of sending communities, the effect of migration on fertility, and projected trends of population decline and aging. The authors conclude by discussing potential long-term threats to the viability of ethnically Tibetan communities in the Himalayan highlands, including outmigration’s effect on agricultural production, the family-based care system for the elderly, socioeconomic inequalities, and human capital.

Supplementary Publications

Biological Stress and Responses

  • Gilbert-Kawai, E. T., Milledge, J. S., Grocott, M. P., & Martin, D. S. (2014). King of the mountains: Tibetan and Sherpa physiological adaptations for life at high altitude. Physiology, 29(6), 388-402. DOI.

  • Beall, C. M. (2007). Two routes to functional adaptation: Tibetan and Andean high-altitude natives. Proceedings of the National Academy of Sciences, 104(suppl 1), 8655-8660. DOI. 

  • Beall, C. M. (2001). Adaptations to altitude: a current assessment. Annual review of anthropology, 30(1), 423-456. DOI.

Genomic Characteristics

  • Bigham, A. W., Wilson, M. J., Julian, C. G., Kiyamu, M., Vargas, E., Leon‐Velarde, F., … & Shriver, M. D. (2013). Andean and Tibetan patterns of adaptation to high altitude. American Journal of Human Biology, 25(2), 190-197. DOI.

  • Beall, C. M., & Leslie, P. W. (2014). Collecting women’s reproductive histories. American Journal of Human Biology, 26(5), 577-589. DOI.

Associating Biological Characteristics with Genotypes

  • Jeong, C., Ozga, A. T., Witonsky, D. B., Malmström, H., Edlund, H., Hofman, C. A., … & Warinner, C. (2016). Long-term genetic stability and a high-altitude East Asian origin for the peoples of the high valleys of the Himalayan arc. Proceedings of the National Academy of Sciences, 113(27), 7485-7490. DOI.

  • Simonson, T. S., & Wagner, P. D. (2015). Oxygen transport adaptations to exercise in native highland populations. DOI.

  • Beall, C. M. (2014). Adaptation to high altitude: phenotypes and genotypes. Annual Review of Anthropology, 43, 251-272. DOI.

  • Petousi, N., & Robbins, P. A. (2014). Human adaptation to the hypoxia of high altitude: the Tibetan paradigm from the pregenomic to the postgenomic era. Journal of applied physiology, 116(7), 875-884. DOI.

  • Petousi, N., Croft, Q. P., Cavalleri, G. L., Cheng, H. Y., Formenti, F., Ishida, K., … & Robbins, P. A. (2014). Tibetans living at sea level have a hyporesponsive hypoxia-inducible factor system and blunted physiological responses to hypoxia. Journal of Applied Physiology, 116(7), 893-904. DOI.

  • Simonson, T. S., Yang, Y., Huff, C. D., Yun, H., Qin, G., Witherspoon, D. J., … & Ge, R. (2010). Genetic evidence for high-altitude adaptation in Tibet. Science, 329(5987), 72-75. DOI.

  • Yi, X., Liang, Y., Huerta-Sanchez, E., Jin, X., Cuo, Z. X. P., Pool, J. E., … & Wang, J. (2010). Sequencing of 50 human exomes reveals adaptation to high altitude. science, 329(5987), 75-78. DOI.

  • Beall, C. M., Cavalleri, G. L., Deng, L., Elston, R. C., Gao, Y., Knight, J., … & Zheng, Y. T. (2010). Natural selection on EPAS1 (HIF2α) associated with low hemoglobin concentration in Tibetan highlanders. Proceedings of the National Academy of Sciences, 107(25), 11459-11464. DOI.