A genetic variation that appears to have boosted medieval Europeans’ ability to survive centuries before the Black Death may contribute — albeit in a small way — to the inflammatory disease afflicting humans today.
Researchers used DNA collected from centuries-old remains to distinguish the fingerprints the bubonic plague left on European immune systems during the Black Death. This fluctuating prevalence of the disease tended to spare those who have a different set of genes ERAP2when investigators report to Oct. 19 nature. Changing that is already known to scientists to slightly increase the odds of developing Crohn’s disease, in which errant inflammation damages the digestive system.
The results show “how these studies on ancient DNA can actually understand diseases even now,” said Mihai Netea, an infectious disease specialist at Radboud University Medical Center in Nijmegen, the Netherlands, who was not involved in the study. “And the trade is by far the most famous.”
By bacteria Yersinia pestisbubonic plague once killed 60 percent of those infected ( .SN: 6/15/22). In the ancient world, it caused successive waves of misery, the most devastating of which is the Black Death, often dated from 1346 to 1350, an episode that wiped out at least 25 million people – about a third or more of Europe. population
For individuals whose immune systems have certain characteristics, pathogens such as Y. pestis have shaped the evolution of the human immune system. Studies have changed the course of a huge fan of genetically modified Europeans immune to the plague.
In this latest study, population geneticist Luis Barreiro of the University of Chicago and colleagues collected DNA samples from the remains of 16 people in London and Denmark who died between 1000 and 1800, including those buried during the Black Death. The researchers examined DNA regions for immune-related genes and regions associated with autoimmune and inflammatory diseases.
Within those regions, the researchers identified four areas of the chromosome where they saw strong evidence of genetic changes that seemed to have been driven by the Black Death. In follow-up work, another change stood out: an increase in the frequency of the variant ERAP2. When infected Y. pestisimmune cells from people with this version ERAP2 kills bacteria more effectively than the variant cells lack. Current population studies have linked the same variants to Crohn’s disease.
While the researchers are calculating ERAP2 variants of the Black Death improved the odds of survival by 40 percent, but slightly increased the risk for Crohn’s disease. For complex disorders like Crohn’s, “there are probably hundreds, sometimes thousands, of genetic variants that increase your risk just significantly,” Barreiro says.
For a long time, researchers in the field have thought that adaptations that helped our ancestors’ immune systems against infectious diseases could contribute to excessive destructive immune activity. Earlier epidemiological studies provide support for this view. Genetic analysis looking for traces of historical disease in modern Europeans and the study of DNA from the remains of the German plague of the 16th century, and vice versa, which appear to be protective mutations against the plague that, like a. ERAP2 vary, and are associated with inflammatory and autoimmune conditions.
Also, this latest discovery suggests that the genetic changes that have boosted the human immune response in the past, enabling it to better fight ancient infections, may come at a cost. “If you turn up too much heat, it induces disease,” says Barreiro.
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