SOCI 2001 week 6 Discussion Essay

The decline of Native American populations after European contact has been linked to several factors including warfare, alterations in social structure and an overwhelming introduction of European-borne pathogens^1,2,3. Although the extent of the population decline remains contentious, European-borne epidemics may have disproportionately contributed to the phenomenon^4,5. The debate has prompted researchers to explore the possibility of genetic susceptibility, where low-genetic variation in HLA genes and immunologically naïve populations are linked to the exacerbated pathogen-associated mortality rates^6,7,8. Assumptions of homogeneity among certain immune genes⁸, however, are based on surveys of living Native Americans who represent the surviving members of communities affected by European contact and colonization. Thus, they fail to consider immune-related genetic factors that may have existed before contact.SOCI 2001 week 6 Discussion Essay

The immunological history of the indigenous people of the Americas is undoubtedly complex. As people entered the Americas and expanded into different regions, ∼15,000–20,000 years before present (BP)^9,10, groups encountered environments with varying ecologies and with relatively little gene flow from other continental populations until European contact¹¹. We hypothesize that indigenous people adapted to local pathogens, resulting in long-lasting changes to immune-related loci. Ancient immune adaptations are suspected to have occurred throughout human history as populations spread into varying environments across the globe¹². If the indigenous people of America adapted to local pathogens, those adaptations would have proven useful in ancient times but not necessarily after European colonialists altered the environment with their pathogens, some of which may have been novel^13,14,15. Existing genetic variation as a result of adaptation before European contact could thus have contributed to the indigenous population decline after European contact.SOCI 2001 week 6 Discussion Essay

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To investigate the possibility of a pre-existing genetic component, we sequenced 50 exomes of ancient and modern individuals from the Northwest Coast of North America, dating from before and after European contact. We confirm the genetic continuity between the ancient and modern individuals, establishing a single continuous population through time. We show a 57% reduction in effective population size after European contact, inferred from our demographic model. We also detect signatures of positive selection on immune-related genes in the ancient but not the modern individuals. The strongest selection signal in the ancients derives from the human leucocyte antigen (HLA) gene HLA-DQA1, with alleles that are close to fixation. The important immune function of HLA-DQA1 supports an ancient adaptation to the environments of the Americas. The modern individuals show a marked decrease in the frequency of the associated alleles (the most pronounced variant showing a 64% difference). This decrease is likely due to the environmental change associated with European colonization, which resulted in a shift of selection pressures, whereby negative selection may have acted on the same gene after contact. Furthermore, the selection pressure shift could correlate to the European-borne epidemics of the 1800s, suffered in the Northwest Coast region. This is among the first studies to examine a single population through time and exemplifies the power of such studies in uncovering nuanced demographic and adaptive histories.SOCI 2001 week 6 Discussion Essay