Tibeten women with higher O2 have more children

Ongoing selection for adaptation to high altitude

Ye, S., Sun, J., Craig, S. R., Di Rienzo, A., Witonsky, D., Yu, J. J., Moya, E. A., Simonson, T. S., Powell, F. L., Basnyat, B., Strohl, K. P., Hoit, B. D., & Beall, C. M. (2024). Higher oxygen content and transport characterize high-altitude ethnic Tibetan women with the highest lifetime reproductive success. Proceedings of the National Academy of Sciences, 121(45), e2403309121. https://doi.org/10.1073/pnas.2403309121

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