Medieval Skeletons Reveal How the Bubonic Plague Influenced Human DNA

As the Black Death decimated medieval Europe’s population, certain genetic variants may have increased some people's chance of survival. Now, in a paper published last week in Nature, researchers suggest one variant might have raised these odds by 40 percent.

But despite the way this gene helped during the bubonic plague, today it plays a small role in causing autoimmune disorders such as Crohn’s disease.

The findings indicate that some genes can be beneficial during a pandemic but also increase the risk of other diseases. “The idea is that we have to keep a balance between both effects to survive, actually, and this is really challenging,” Alicia Sanchez-Mazas, head of the Laboratory of Anthropology, Genetics and People in History at the University of Geneva in Switzerland, who did not contribute to the paper, tells Stat News’ Brittany Trang.

Yersinia pestis, a bacteria species spread by fleas, causes the bubonic plague. In the mid-14th century, the disease killed between 30 and 50 percent of all people living in Europe, the Middle East and Africa, writes Science’s Ann Gibbons. It was the deadliest pandemic on record.

Scientists had already hypothesized that plague survivors could have passed on protective genes to their descendants. Since so many people died, they presumed the catastrophe could have changed the genetic makeup of Europe, the New York Times’ Carl Zimmer reports.

Such an idea, however, is difficult to test. It is “not feasible” to detect the plague’s influence in the DNA of people alive today, Anne Stone, a molecular anthropologist at Arizona State University, Tempe, who did not contribute to the research, tells Science.

But by using modern techniques for analyzing ancient DNA, the team was able to examine the remains of people who lived before, during and after the Black Death. They studied the genes of 318 people buried in three London cemeteries between 1000 and 1500, as well as 198 people from Denmark who lived between 850 and 1800, per the Times.

The team looked for genetic variants that were less prevalent in people killed by the Black Death and more common in people who lived after the pandemic, since these might have contributed to immunity, per Stat News. They found four variants fitting this pattern in both the British and Danish groups.

Of particular interest was a gene called ERAP2, which makes a protein that helps defend against pathogens, per the Times. The researchers found two variants of ERAP2 in the ancient DNA, one of which provided more immunity, according to Science. Each person has two copies of ERAP2, but whether they have the more protective or less protective versions—or one of each—varies.

The researchers exposed blood from modern humans to the plague-causing bacteria. As the team predicted, immune cells from people with two protective copies of ERAP2 were more successful at killing the pathogen than cells with one or zero copies, per Stat News.

In the ancient DNA portion of the study, scientists revealed that people with two protective copies of the gene were 40 percent more likely to survive the plague, per the Times. “It’s actually shocking,” David Enard, an evolutionary biologist at the University of Arizona who did not contribute to the research, says to the Times.

The study also found that while 40 percent of the Londoners had one or two copies of the protective variant before the plague, that number rose to more than 50 percent within a few generations, per Science. Monty Slatkin, a population geneticist at the University of California, Berkeley, who did not contribute to the paper, tells Science that the increase is among the fastest examples of natural selection ever detected in humans.

“This is a truly impressive paper,” Enard says to Science. “The implications of the potential speed and power of natural selection in immune genes are wild.”

But these variants that protect the body against invaders also increase the risk of autoimmune diseases, in which the body attacks itself. Genes identified in the new study have previously been tied to Crohn’s disease, rheumatoid arthritis and lupus, per Stat News.

Luis Barreiro, a population geneticist at the University of Chicago and a co-author of the new study, notes to Science News’ Wynne Parry that the ERAP2 variant only has a small impact on the risk of Crohn’s. For such complex diseases, “you require probably hundreds, sometimes thousands of genetic variants to actually increase your risk in a significant manner,” Barreiro tells the publication.

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Will Sullivan is a science writer based in Washington, D.C. His work has appeared in Inside Science and NOVA Next.