Scientists discover genetic variation that offers largest evolutionary advantage found in humans
A study published in Nature two weeks ago identified a genetic variation that gave certain people a 40% chance of surviving the Black Death—the largest evolutionary advantage found in humans. The Black Death, a plague that spread throughout Europe, the Middle East, and North Africa ravaged the human race between 1346 and 1351. The population was reduced by up to 30 to 50%. The Black Death was the second-ever recorded pandemic outbreak in history, the first being the Plague of Justinian in 541 CE. As a result, people living during the Black Death’s height had no recent exposure to any plague, meaning they were highly susceptible to Yersinia pestis, the bacterium responsible for bubonic plague that is spread by fleas. The sheer devastation the Black Death brought was immense, and it impacts our species to this day.
Recently, a team of scientists discovered that natural selection brought on by the selective pressures of the Black Death led to genetic variations that helped certain people survive the Black Death. These variations are still apparent in some people’s genes today. Hendrik Poinar, an evolutionary geneticist at McMaster University in Hamilton and a senior author of the study, wrote that “We’re still living in the shadow of the Black Death.” The goal of the study was to look at how the genes that regulate our immune system were impacted by the plague. In order to do this, Jennifer Klunk, a lead product scientist at Daicel Arbor Biosciences in Ann Arbor, Michigan traveled to Denmark and the United Kingdom to collect DNA samples from excavated burial sites dating back to the Black Death. Referring to the plague, Klunk said, “If anything is going to cause selective pressure on the human genome, that’s probably a great place to look.”
In total, the study screened 516 samples of DNA (318 from London; 198 from across Denmark), including 42 victims of the Black Death. By comparing the bones from before and after the plague, the researchers were able to deduce differences in DNA. There were hundreds of mutations in genes involved in immunity that researchers discovered after the Black Death. In particular, the scientists found that carrying two versions of a gene called ERAP2 made people 40% likelier to survive the Black Death. According to Dr. Barreiro, this is the largest evolutionary advantage ever found in humans. Notably, ERAP2 makes a protein involved in the immune response to bacteria and viruses, which is why those whose cells which carried both versions of the ‘protective’ variant that killed Yersinia pestis efficiently. To determine if the change was related to the plague, a second part of the study was conducted at the Pasteur Institute in Paris. There, researchers tested immune cells donated by individuals with different versions of the ERAP2 gene. Those with the protective version of ERAP2 killed the Yersinia pestis efficiently, cells without the protective gene had little effect against the bacteria, while those with one copy of the gene only exhibited an intermediate effect.
This study provides strong empirical evidence that the Black Death was an important selective pressure that shaped genetic diversity in relation to immune response. This genetic variation may have made people more likely to survive the plague, but according to Poinar, there are unfortunate side effects of the long-term selection for protection. People who inherit the plague-resistant mutations of the double protective cell run a higher risk of immune disorders, such as Crohn’s disease. This is because ERAP2 protection can lead to one’s immune system being “superefficient” and reacting too frequently to friendly bacteria in the gut, causing inflammation. This study not only finds that ERAP2 offers the largest evolutionary advantage ever found, but it also links the selective force of past pandemics to present-day susceptibility to auto-immune disease. In comparison, it is unlikely that COVID-19 will have a strong impact on human evolution. Thanks to the advent of vaccines, those who have died are often older individuals who have already passed on their DNA.