(2015-05-15) Brown, Elizabeth; Ruvolo, Maryellen; Sabeti, Pardis; Capellini, Terence D.
Diverse climates, infectious agents, and subsistence patterns drove humans to adapt metabolically to different environments since the migration out of Africa 100,000 years ago. In this dissertation, I review current literature on the genetic underpinnings, and the molecular and physiological manifestations of these metabolic adaptations in diverse human populations. Then, I develop a theory regarding pregnancy as a critical period in life history that mediated recent selection on human metabolism. Finally, I investigate the function and evidence for selection of derived genetic variants at increased frequency in East Asian populations. I find multiple standing variants that increase expression of the gene IVD and increase the efficiency of leucine catabolism, which lie on positively selected haplotypes in East Asians. I use this research process as a model for how to develop and study novel hypotheses of human metabolic adaptation. Such adaptations often impact health in the modern environment, so more evolutionary research will provide useful guidance to the medical community in how to treat people from diverse ethnicities.
