Our Microbes, Ourselves: Exploring Human-Pathogen Coevolution through the Lens of Ancient DNA

Abstract

Infectious diseases have had a profound impact on the course of human evolution, exerting selective pressures that altered the genome and shaped human behaviors. In turn, through our interactions and migrations, humans have spread pathogenic microbes around the globe, while technological and cultural developments have opened new niches in which these microorganisms can thrive. Recent developments in the field of ancient DNA have made it possible to reconstruct genome-wide data from these pathogenic microbes preserved in human skeletal material. In the introduction, I summarize these methodological advancements and illustrate ways in which these new paleopathogenomic datasets provide a lens for exploring our species’ evolutionary past. The remainder of this thesis presents two new ancient DNA datasets that shed light on classic case studies of host-pathogen coevolution: (1.) the human malaria parasites Plasmodium falciparum and Plasmodium vivax, and (2.) the cariogenic oral pathobiont Streptococcus mutans. In Chapter 1, I explore the evolution of human malaria, a disease which has impacted the human genome perhaps more than any other. Despite its evolutionary relevance, important gaps remain in our knowledge of the origin and dissemination of the malaria parasites P. falciparum and P. vivax, as well as how parasite genomics, population history, and evolution have shaped differences in the physiology, epidemiology, and virulence of these two species. I present the first genome-wide ancient mitochondrial and nuclear data from three malaria parasite species: P. falciparum, P. malariae, and P. vivax. Analyzing 36 ancient malaria cases spanning 5,500 years of human history, I highlight the key role of human mobility and migration in malaria transmission, from the individual to the transcontinental scale. In presenting the population structure of a global set of ancient Plasmodium strains, our study sets the stage for further attempts to unravel malaria’s history and evolution using ancient DNA. In Chapter 2, I present a second coevolutionary case study that illustrates the potential impact of human behavioral and technological developments on pathogenic microbes: that of the cariogenic oral pathobiont S. mutans. One of the most profound dietary shifts in our species’ evolutionary history, the adoption of agriculture impacted many aspects of human health. While consumption of starchy staple crops is linked to higher caries rates among agricultural populations, the potential role of oral microbes like S. mutans remains to be explored. In this study I present genome-wide data from a global set of 79 ancient S. mutans strains spanning the Mesolithic to the modern era. Using a pan-genomic approach, I explore whether changes in human diets impacted the virulence and functional capacity of this pathobiont, potentially contributing to its cariogenic potential. Finally, in Chapter 3, I contextualize these two co-evolutionary case studies within broader trends shaping the field of paleopathogenomics. The depth and breadth of ancient DNA datasets is increasing rapidly, presenting both new opportunities and novel challenges for studies seeking to explore the evolutionary history of human pathogenic microbes. Building on lessons learned through analysis of the two case studies presented in this thesis, I outline several technical, methodological, and interpretative problems facing future paleopathogenomic studies. Finally, I offer a perspective on how the field of ancient pathogenomics may develop in the coming years, providing exciting new opportunities to explore our species’ evolutionary past using ancient microbial DNA.