Evidence for Natural Selection in High Altitude Human Populations
Open Access
- Author:
- Bigham, Abigail Winslow
- Graduate Program:
- Anthropology
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- September 22, 2008
- Committee Members:
- Mark Shriver, Dissertation Advisor/Co-Advisor
Mark Shriver, Committee Chair/Co-Chair
Kenneth Monrad Weiss, Committee Member
Jeffrey Arnold Kurland, Committee Member
Kateryna Dmytrivna Makova, Committee Member - Keywords:
- HIF pathway
Hypoxia
Natural Selection
High Altitude
Andes
Tibet - Abstract:
- High altitude environments, wherein geographically distinct human populations have adapted, provide scientists with a natural laboratory to study the effects of selective pressures on human variation. My dissertation research focuses on identifying positive directional selection in response to high altitude hypoxia using independent, highland populations compared to low altitude control populations. The high altitude populations of interest are those of the Andes and the Tibetan Plateau. The low altitude control populations are from Asia, the Americas and Europe. Three major questions are addressed by this research: 1) Is there evidence for natural selection among populations of the Tibetan Plateau? 2) Is there evidence for natural selection among populations of the Andean Altiplano? 3) Do the Tibetan and Andean populations exhibit similarities or differences in genes or functionally different changes in the same genes involved in high altitude adaptation? In order to answer these questions, this project was divided into two distinct phases of research. In part 1, candidate genes were identified and screened for evidence of positive directional selection using genome scan data generated from the Affymetrix Inc. 1-Mega WGA SNP Chip. This phase was administered separately for the Andean versus the Tibetan populations and the results of the analyses compared. By independently searching for signatures of selection in Andean populations versus Tibetan populations, this research identified similarities and differences in the genetic adaptive mechanisms of these two populations. Part 2 used admixture-mapping analysis to test for associations between selection nominated candidate genes identified in part 1 of this research with pregnancy related phenotypes collected at both high and low altitude in a population sample comprised of European and Bolivian women. By understanding how similar environmental pressures can result in either the same or different genetic adaptations, we will be better situated to understand the molecular basis for convergent human adaptations. I hope this research will establish a basis for comparative studies looking at the process of genetic adaptation in human populations.