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European conquest of North America had a devastating effect on its indigenous people. Warfare, forced migration and the resulting social upheaval decimated the populations of Native Americans, but perhaps nothing had a greater impact than the spread of diseases like smallpox. Scientists have long wondered whether Native Americans were susceptible to European-borne diseases simply because they hadn't been exposed, or if they were somehow more susceptible to pathogens carried by invaders.
A new analysis of DNA from Canadian First Nations individuals suggests that genetic adaptions were at least part of the explanation. The study, published earlier this month in Nature Communications, shows big differences in immune system genes before and after European contact, suggesting that while these people had been well adapted to their environment before colonization, those who survived the epidemics rapidly developed immune system adaptations to protect against the new threats. John Lindo, a postdoctoral scholar in human genetics at the University of Chicago, led a team that analyzed exome data-the subset of DNA that encodes protein needed for biological functions-from communities in the Prince Rupert Harbor region of British Columbia, Canada. This included 25 ancient samples, some more than 6,000 years old, taken from archaeological sites and 25 living individuals from modern Coast Tsimshian communities in the same area.
Lindo and the team first used the DNA to confirm oral histories and archaeological records showing that the modern individuals were indeed from the same ancestral population as the ancient samples. They then modeled the population history of the groups, and identified a 57 percent population decline about 175 years ago-corresponding with historical records of large smallpox epidemics. When they scanned the samples for signs of positive selection-widespread, high frequencies of gene variants that indicate some genetic advantage-one gene stood out. One variant of HLA-DQA1, a gene directly involved in the immune system, was present in nearly 100 percent of the ancient individuals but only 36 percent of the modern ones.
Instead, a different variant took its place in a span of about 150 years. "It looks like an immune gene was selected for in the ancient population, which suggested that there were pathogens that could've existed when they first came into the Americas or particularly that region," Lindo said. But did that version of the gene make the ancient Tsimshian people more vulnerable to smallpox? "You can't say that," Lindo said. "They were adapted to something else it seems, and then they quickly readapted to provide some sort of resistance potentially to the survivors of these pathogens." Lindo said the rapid shift from one gene variant to another in such a short amount of time is astonishing in human genetic terms. "We wouldn't have been able to detect it by using modern DNA alone," he said. "But in adding the ancient DNA component, we're seeing evolution happen essentially in humans for one of the first times. We've actually seen this shift happen in terms of genes, and can now correlate it to epidemics."