Post-contact evolutionary immunogenetics in Indigenous peoples of America

Abstract

Upon European colonisation in the 15th century, Indigenous populations across the Americas were expansive, with total census numbers across both continents totalling approximately 75 million. However, these populations declined rapidly and extensively upon contact, falling at regional rates of 80-95% until the beginning of population recovery in the early 1900’s. Historians and anthropologists have attributed this precipitous decline to the introduction of European infectious diseases such as smallpox, influenza, tuberculosis, and measles, as well as the societal upheavals, warfare, and other socially oppressive impacts of early colonization. Despite the widespread recognition of disease impacts of colonisation, the genetic effects of introduced infectious diseases on Indigenous populations has not been well investigated. Most studies thus far have focussed on genetic evolution in modern Indigenous populations, with few including comparisons to other world populations, and even fewer using time-series analyses to establish immunity adaptation prior to European contact. Considering the introduction of pathogens and scale of societal collapse, the impact of European colonisation was arguably one of the most disruptive events in the recent history of Indigenous peoples of America. Since pathogens are known to exert a strong selective pressure in humans, and that a large influx of different types of pathogens (bacteria, parasites, fungi, and especially viruses) accompanied Europeans during the colonial expansion, the change in pathogenic landscape adaptation of Indigenous peoples is expected to have been drastic. This likely resulted in large immune gene changes which are yet to be characterised. Investigating these adaptive processes and their dynamics with colonial-introduced infectious diseases hold much potential for uncovering adaptive mechanisms, as well as better contextualisation of current disparities in Indigenous infectious disease burden. Holistic insights into both past and present adaptation in immunity genes may also inform our broader understanding of human adaptation to pathogens, possibly elucidating new candidate genes and pathways that may be ubiquitous targets of selection. This understanding is becoming more urgent in the face of novel and emerging infectious diseases, for which early detection and development of vaccines and other medical measures is instrumental to minimising loss of life. This is exemplified in the recent Covid-19 epidemic, for which extensive research and vaccine development has been crucially important. This thesis provides new perspectives on evolutionary immunogenetics in Indigenous peoples of America upon contact with Europeans. First, I take a multidisciplinary approach in examining evidence and theories underlying the impact of European-introduced diseases on the genomes of Indigenous populations. I examine the anthropological and historical narratives and paradigms commonly used to describe the depopulation. I then build a picture of the differences in host-pathogen co-evolutionary histories between European and Indigenous populations since their ancestral divergence, using key observations from paleomicrobiolocal evidence. I summarise the findings from studies investigating the impacts of colonisation from a genetics perspective, including the post-contact demographic bottleneck, admixture-enabled selection from global population movements under colonial rule, and possible immune adaptation described for ancient and modern populations. This provides a holistic, thorough contextualisation of post-contact immune gene adaptation in the Americas. Using ancient DNA samples and population genetics methods, I then reconstruct a demographic history for time-series data from Indigenous Andean populations, spanning from around 2900 years ago to present day. I use several methods in determining genetic differentiation at genome-wide single nucleotide polymorphisms. This approach reveals putative signals of selection acting upon immunity genes and pathways both in ancient and modern populations, with an especially remarkable strength in immune signals for the ancient North Coast population. No signals are apparent for genes associated to smallpox or influenza, which is contrary to the adaptation signals we expected. I also find a strong differentiation signal between ancient and modern individuals in genes important to HIV response, along with putative signals for four oncogenic viruses that are known to be particularly pathogenic in HIV-associated immunosuppression. In addition to the genome-wide approach taken in Chapter II, I also take a closer look at a crucial, front-line member of the immune system, the Human Leukocyte Antigen (HLA) cluster, in modern Indigenous people of America and other world populations. Using machine learning methods, I examine the binding affinity of HLA alleles to various proteomes from several pandemic viruses and quantify these differences across world populations. Indigenous populations from both North and South America show very different patterns to any other global population, with significantly higher frequencies of strong binders and lower frequencies of weak binders, a result that is striking and possibly indicative of post-contact adaptation.