When the indigenous peoples of the Americas encountered European settlers in the 15th century, they faced people with wildly different religions, customs, and—tragically—diseases; the encounters wiped out large swaths of indigenous populations within decades. Now, researchers have found that these diseases have also left their mark on modern-day populations: A new study suggests that infectious diseases brought by Europeans, from smallpox to measles, have molded the immune systems of today’s indigenous Americans, down to the genetic level.

The immune system is a complex structure, built over a person’s life in response to environmental conditions. Antibodies, proteins that tag and attack viruses and bacteria, “remember” past invaders, allowing white blood cells to quickly respond during subsequent infections. Because different groups of people encounter different diseases—the European settlers had high exposure to smallpox, measles, and influenza thanks to close contact with livestock—they develop different antibodies. But what about the genes behind the immune system? Could those also change vulnerability to certain diseases?

To find out, a team led by Ripan Malhi, an anthropologist at the University of Illinois in Urbana, sought permission from the Tsimshian, a First Nations community in the Prince Rupert Harbor region of British Columbia in Canada, to examine DNA from the skeletal remains of 25 individuals who lived in the region between 500 and 6000 years ago. These ancient indigenous inhabitants, many of them ancestors to the modern Tsimshian, were a seafaring people who first encountered Europeans in the early 1700s.

Using a technique known as whole exome sequencing, researchers—including Tsimshian scientists Barbara Petzelt and Joycelynn Mitchell—sifted through the DNA for genes related to immune response. They then sequenced DNA samples from 25 Tsimshian living near Prince Rupert today. Comparing the two sets of genes, the team discovered several immune-related gene variants that were rare among the living. For example, a variant of a gene known as a HLA-DQA1, which codes for proteins that sort healthy cells from invading viruses and bacteria, was found in nearly 100% of ancient individuals, but in only 36% of modern ones.

That finding suggests that the immune-related genes of the ancient Tsimshian were well-adapted to local diseases but not to novel infections like smallpox and measles, the team reports today in Nature Communications . Because European-borne epidemics altered the disease landscape, survivors were less likely to carry variants like HLA-DQA1, which were less able to cope with the new diseases (precisely how is still a mystery). “Those ancient genetic variants that were once adaptive were no longer adaptive after European contact,” Malhi says.

Measuring differences between the ancient and modern DNA, Malhi and colleagues calculated a rough date for the genetic shift, about 175 years ago. At that time, smallpox epidemics raged throughout the Americas, including in Prince Rupert Harbor. Those with the most susceptible immune system genes were killed. Based on the new findings and historical accounts, the team says that close to 80% of the community died in the decades following initial European contact.

Kim TallBear, a native studies researcher at the University of Alberta in Edmonton, Canada, says the study is well designed and provides “deeper genetic resolution on what we already know.” Still, she’s concerned the paper suggests that indigenous people are defined by their differences with Europeans, rather than by their adaption to their own environment. “Within the dominant scientific narrative, the European body is the standard and indigenous bodies are thought of as biologically deviant,” TallBear says.

Going forward, Malhi plans to investigate the immune-related genes of other indigenous communities. Jennifer Raff, an anthropologist and geneticist at the University of Kansas in Lawrence, agrees that it’s an important question going forward. “Different tribes had different experiences of contact,” she says. “It’s critically important to study the specific genetic consequences in populations across the Americas.”