A genetic variant that appears to have increased the ability of medieval Europeans to survive the Black Death centuries ago may contribute, albeit in a small way, to an inflammatory disease that affects people today.
The researchers used DNA collected from centuries-old remains to discern the fingerprints left by the bubonic plague during the Black Death on the immune systems of Europeans. This devastating wave of disease tended to forgive those who possessed a variant of a gene known as ERAP2causing it to become more common, researchers report Oct. 19 in Nature. Scientists already know that variant to slightly increase the odds of developing Crohn’s disease, in which wandering inflammation damages the digestive system.
The results show “how these studies on ancient DNA can help understand diseases even now,” says Mihai Netea, an infectious disease specialist at Radboud University Medical Center in Nijmegen, the Netherlands, who was not involved in the study. “And the compensation is also very clear.”
caused by the bacteria Yersinia pestisbubonic plague once killed 60 percent of those infected (Serial number: 06/15/22). In the ancient world, it caused successive waves of misery, the most devastating of which was the Black Death, often dated between 1346 and 1350, an episode believed to have wiped out at least 25 million people, roughly a third or more of the European population. population.
By not affecting people whose immune systems have certain characteristics, pathogens such as and pestis have shaped the evolution of the human immune system. Studies are unraveling the ways in which the massive elimination of the plague altered genetics related to the immune system of Europeans.
In this most recent study, population geneticist Luis Barreiro of the University of Chicago and colleagues collected samples containing DNA from the remains of 516 people in London and Denmark who died between 1000 and 1800, including those buried during the Black Death. The researchers examined stretches of DNA for genes related to the immune system and areas associated with autoimmune and inflammatory diseases.
Within those regions, the researchers identified four locations on the chromosomes where they saw strong evidence of genetic changes that appeared to have been driven by the Black Death. In follow-up work, one change stood out: an increase in the frequency of one variant of ERAP2. When infected with and pestisimmune cells from people with this version of ERAP2 it killed bacteria more effectively than cells lacking the variant. Modern population studies have linked this same variant to Crohn’s disease.
Although the researchers estimate that the ERAP2 variant improved the odds of surviving the Black Death by up to 40 percent, only slightly increasing the risk of Crohn’s disease. For complex disorders like Crohn’s disease, “it probably takes hundreds, sometimes thousands of genetic variants to increase risk significantly,” says Barreiro.
For some time, researchers in the field have theorized that the adaptations that helped our ancestors strengthen their immune systems against infectious diseases may contribute to excessive and damaging immune activity. Previous studies on the plague offer support for this idea. A genetic analysis for traces of historical diseases in modern Europeans and a study of DNA from the remains of 16th-century German plague victims both exhibited what appear to be protective changes against the plague that, like the ERAP2 variant, are linked to inflammatory and autoimmune conditions.
Similarly, this latest discovery suggests that genetic changes that have boosted the human immune response in the past, allowing it to better fight old infections, may come at a cost. “If you turn the heat on too high, that leads to illness,” says Barreiro.