Doctoral Dissertation Research: Investigating the Evolution of the Human Adaptive Immune Response

Pathogens have been a major selective pressure throughout human evolution and continue to be a major problem in human populations today. The transition of many human groups from foraging to agriculture marks one of the largest changes in the human pathogenic environment. The change in this pathogenic landscape likely created unique selection pressures on genes involved in immune response. However, the impact that the transition to agriculture had on the evolution of the innate immune system and how this varies across human populations is still poorly understood. This project advances knowledge of the impacts of this transition to agriculture on human immune genes and their expression with genomic data from historically foraging and agriculturalist communities. The project supports community-engaged research collaborations and science outreach activities as well as undergraduate and graduate training in STEM. The investigators collect genome-wide SNP and transcriptomic data from two communities to test the hypothesis that signatures of selection and immune gene expression patterns vary between forager and agriculturalist populations. The research activities include 1) identifying signals of natural selection on immune genes in both populations, and 2) characterizing forager and agriculturalist-specific transcriptomic responses to viral and bacterial pathogens using in vitro experiments on white blood cell samples. Understanding how different populations adapted to changes in subsistence strategy can provide valuable insight into the long-term co-evolutionary relationship between humans and microbes. In addition, the project focus on the biological function of putatively selected variants is an important advance in the field beyond mere identification of the variants. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.