Human Adaptation to Changing Diet and Infectious Disease Loads, from the Origins of Agriculture to the Present. (360G-Wellcome-100719_Z_12_Z)

Modern patterns of human health and disease have been shaped by cultural, demographic and ecological changes over the last 10,000 years, particularly in association with the transition to agriculture and subsequent increases in urban settlement, population density and mobility, and reduction in dietary breadth to a few key staples. These changes will, in turn, have led to increased carbohydrate consumption and glycaemic loads, infectious disease loads, and the potential for zoonotic transmission . Natural selection will have acted upon human genetic variation in response to these changes, particularly that involved in diet and infection, and the detection of signals of natural selection provides a clear-cut means of identifying medically-relevant genetic variation in past populations, since it identifies variants that affected survival. While many methods and studies have been aimed at detecting recent natural selection, none can be as sensitive as the direct comparison of allele freque ncies at different time points in continuous human populations. Furthermore, this approach is currently the only means of assessing temporal heterogeneity in natural selection. We propose to quantify the tempo and extent of evolutionary response to infectious disease loads and dietary change in Europe by applying a candidate gene, high-throughput capture-based approach to both archaeological and modern samples. We will also integrate archaeological and historical data to assess the impact of key transitions in diet, demography, economy and settlement on health.