The Black Death was the most lethal pandemic in human history, and geneticists have long been curious about its origins and its impact on human migrations and immunity. “It’s just unimaginable,” says Luis Barreiro, a human population geneticist at the University of Chicago in Illinois.
Barreiro and his colleagues hypothesized that such a dramatic event could have left its mark on the evolution of the immune system. To find out, they looked at genetic variation in more than 200 DNA samples isolated from the bones or teeth of individuals who lived before the plague, died from it or lived one or two generations later.
Barreiro and his collaborators speculated that having a full-length, fully functional ERAP2 protein might have improved immune protection during the Black Death. Laboratory studies backed up this idea: macrophages expressing the longer version of ERAP2 were able to keep Yersinia pestis from replicating more effectively than were macrophages expressing the truncated version.
But the protective ERAP2 gene variant is also a known risk factor for Crohn’s disease. Another of the variants Barreiro and his colleagues found is associated with rheumatoid arthritis and another autoimmune condition, systemic lupus erythematosus. This, says Barreiro, highlights the relevance of studying the evolutionary pressures that might select for these variants: “These variants can also today impact sensitivity to immune-related disorders.”
