A genetic variant that appears to have boosted medieval Europeans’ ability to survive the Black Death centuries ago may contribute — albeit in a small way — to an inflammatory disease afflicting people today.
Researchers used DNA collected from centuries-old remains to discern the fingerprints that bubonic plague during the Black Death left on Europeans’ immune systems. This deadly disease was the result of a terrible epidemic People who had a particular gene variant were generally sparedAlso known as ERAP2Researchers report that it is becoming more common. Nature. That variant is already known to scientists for slightly increasing the odds of developing Crohn’s disease, in which errant inflammation harms the digestive system.
The results show “how these studies on ancient DNA can help actually understand diseases even now,” says Mihai Netea, an infectious diseases specialist at Radboud University Medical Center in Nijmegen, Netherlands, who was not involved with the study. “And the trade-off is also very clear.”
Caused By the bacterium Yersinia pestisBubonic plague was once fatal to 60 percent of infected people (SN: 6/15/22). In the ancient world, it caused successive waves of misery, the most devastating of which was the Black Death, often dated from 1346 to 1350, an episode thought to have wiped out at least 25 million people — about a third or more of the European population.
Individuals with certain immune traits are protected from pathogens like Y. pestisThe evolution of the immune system has been influenced by these factors. Studies are teasing out the ways the massive winnowing of the plague altered Europeans’ immune-related genetics.
Luis Barreiro (University of Chicago) and his collaborators collected DNA samples from 516 individuals who died in London or Denmark between 1000 and 1800. This included those who were buried during and after the Black Death. Researchers examined DNA to identify immune-related genes as well as areas that are associated with autoimmune or inflammatory diseases.
The researchers found four areas on chromosomes in these regions where strong evidence was provided that genetic changes were caused by the Black Death. One change was noticed in the follow-up work: an increase of a variant ERAP2. If infected Y. pestisThis version of the virus causes immune cells to be unable to function properly in people. ERAP2Cells without the variant of the gene killed bacteria more effectively than those with it. Studies of modern populations have linked that same variant to Crohn’s disease.
The researchers estimate that the ERAP2 variant improved the odds of surviving the Black Death by as much as 40 percent, it only slightly increases the risk for Crohn’s disease. For complex disorders like Crohn’s, “you require probably hundreds, sometimes thousands of genetic variants to actually increase your risk in a significant manner,” Barreiro says.
Researchers in the field have suspected for some time that adaptive mechanisms that protected our ancestors from infection may also be responsible for excessive immune activity. Studies of plague from the past support this theory. AGenetic analysis is used to determine if there are any traces of historical diseases in the European population.An analysis of DNA taken from 16th-century German plague victimsBoth showed what appeared to be protective measures against the plague. ERAP2Variants are associated with inflammatory or autoimmune conditions.
This latest discovery also suggests that genetic modifications that in the past have boosted the immune system, empowering it against ancient infections, may come with a price. “If you turn the heat too much, that leads to disease,” Barreiro says.
