Prehistoric America was not a disease-free utopia. Tuberculosis, treponemal disease, Chagas disease, and many other pathogens were endemic to populations in different regions of the continent. But the “Columbian Exchange” beginning in 1492 introduced new pathogens to American populations, including smallpox, measles, influenza, and yellow fever. This introduction had devastating consequences for tribes. In some places, death from infectious disease resulted in the depopulation of entire regions, leading to the collapse of social, economic, and political institutions, and the loss of many traditional cultural practices and ways of life.

Understanding the dynamics of these pandemics is critically important in order to learn how they may have shaped the genetic diversity of contemporary Native American communities, potentially giving insights into the genetic underpinnings of diseases present in a higher frequency in some populations than elsewhere. More broadly, documenting the historical effects of the introduction of novel pathogens can give insights into the evolution of host-pathogen relationships. These insights are potentially useful for responding to future outbreaks of emerging infectious diseases.

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It has long been hypothesised that tens of thousands of years of separation and independent evolution from Old World populations rendered the indigenous inhabitants of the Americas immunologically vulnerable to their pathogens. The resulting outbreaks of disease - the so-called “virgin soil epidemics” - following first exposure to these pathogens were therefore particularly devastating. But because many of these diseases leave no trace of infection in skeletons, it has been impossible to fully test this model using only osteological approaches.

However, our ability to recover DNA from past populations gives us a new, powerful way to document the evolutionary effects of these pandemics. For example, a recent study by Lindo et al. (2016) investigated whether there had been changes in immunological genes in the Tsimshian people from the Northwest Coast of North America in response to the introduction of new diseases.

In partnership with the Tsimshian community, researchers compared DNA from contemporary and ancestral populations in the region. By modelling fluctuations in estimated population sizes over thousands of years, they confirmed that the population experienced a severe genetic bottleneck (57% decrease in effective population size) after European contact, about 175 years before present. This bottleneck would have coincided with historically documented smallpox epidemics within the Tsimshian community.

To assess whether there had been changes within immune system-related genes in the Tsimshian population in response to smallpox introduction, the researchers then scanned exomes (the subset of genomic regions which code for protein) from the ancient and contemporary populations. They found evidence for strong positive selection on the regulatory region of the human leucocyte antigen gene HLA-DQA1 in the ancient population. This strong positive selection would have maintained a specific DNA sequence motif in this region from generation to generation, regulating the expression of the HLA gene in a way particularly adaptive for the ancient environment.

However, contemporary Tsimshian descendants’ HLA genes look quite different from their ancestors. Simulations of different evolutionary scenarios suggested that a selection pressure shift in response to a changing pathogen landscape best fit the observed data. Without positive selection maintaining the same genetic motif in the HLA-DQA1 regulatory region, it is free to accumulate mutations which likely have changed the expression of this gene. So although ancient Tsimshian populations were adapted to specific pathogens present in their environment, the introduction of new pathogens by European settlers meant that what was adaptive for one environment was suddenly maladaptive. The resulting population collapse, recorded in both historical documentation and the genetic legacy of contemporary Tsimshian descendants, was one of the tragic consequences.

Infectious diseases were just one of the causes of the profound disruption to indigenous American populations following European contact. Warfare, forced relocations, slavery, suppression of traditional subsistence activities, and the dismantling of social structures and cultural practices all contributed substantially to depopulation. But by showing specifically how their evolution was impacted by changing environments, ancient DNA research offers the potential to yield new insights into the varied experiences and consequences of European contact in different Native American tribes.

Further reading

Lindo, J. et al. A time transect of exomes from a Native American population before and after European contact. Nat. Commun 7: 13175 doi: 10.1038/ncomms13175 (2016).