Person:

Brown, Elizabeth

When considering selective forces shaping human evolution, the importance of pregnancy to fitness should not be underestimated. Although specific mortality factors may only impact upon a fraction of the population, birth is a funnel through which all individuals must pass. Human pregnancy places exceptional energetic, physical, and immunological demands on the mother to accommodate the needs of the fetus, making the woman more vulnerable during this time-period. Here, we examine how metabolic imbalances, infectious diseases, oxygen deficiency, and nutrient levels in pregnancy can exert selective pressures on women and their unborn offspring. Numerous candidate genes under selection are being revealed by next-generation sequencing, providing the opportunity to study further the relationship between selection and pregnancy. This relationship is important to consider to gain insight into recent human adaptations to unique diets and environments worldwide.

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.