Keynote Lecture

Keynote Lecture:

Physiology, fertility, and population genetics of Tibetan highlanders

4:30-5:30 pm, Alumni Hall Auditorium, Open to the public

Adaptations resulting from natural selection can be difficult to detect because biological characteristics reflect both heritable and nonheritable factors. This study accounted for social, economic, and public health influences while testing the hypothesis that relatively low hemoglobin concentration associated with reproductive success in a sample of 1,006 post-reproductive Tibetan women residing at altitudes from 3000m-4100m in Nepal.

We collected reproductive histories by interviews in native dialects and DNA from saliva samples. Poisson and binomial regression analyses selected influential covariates of the number of pregnancies, livebirths, and children surviving to 15. We conducted genome​ ​wide​ ​association studies using 3.5 million single​ ​nucleotide polymorphism sites.

Apart from physiological phenotype, the largest reproductive disadvantages accrued to women who never married or had a late first birth. The largest reproductive advantages accrued to women residing in one of four subdistricts or had a late last birth. Taking such factors into account, higher hemoglobin concentration associated with poorer reproductive success measured as the probability a pregnancy progressed to a livebirth. We detected a genome​ ​wide significant association of EPAS1 variants with oxygenated hemoglobin concentration, consistent with previous reports, but these did not associate with pregnancy outcome. Loci with no known relationship with oxygen homeostasis associated significantly with numbers of pregnancies and live birth with large effect sizes.

The findings illustrate the complexity of identifying adaptations. They support the hypothesis that selection is acting against elevated hemoglobin concentration or another correlated trait among Tibetans at high altitude.

About Dr. Beall

Dr. Cynthia Beall is a Distinguished University Professor and the Sarah Idell Pyle Professor of Anthropology at Case Western Reserve University. Dr. Beall's research focuses on the question "How do humans adapt to life at high altitudes?" Her work to date has provided crucial insights into the physiological and genetic mechanisms enabling humans on three different continents to thrive in highland environments low in oxygen. Dr. Beall continues to explore modern human evolution using a variety of techniques, from field work on the Tibetan Plateau to visualizing blood vessels using sophisticated microscopy to measuring nitric oxide metabolism and to analyzing genome-wide genetic data. She has also appeared in the BBC documentary "Are we still evolving?" Read more about some of Dr. Beall's work here and here, or check her website for more information.