The bubonic plague epidemic of 1346-1350 changed the human genome, playing the role of a factor in natural selection. Due to the significant number of victims, this epidemic was called the Black Death, where 30-50% of the population of Europe, the Middle East, and North Africa died.
Mortality in subsequent epidemics was lower. Although this could be due to the evolution of the plague bacillus or a change in cultural practices, scientists have found that the main reason is the human genetic adaptation to the disease.
Bubonic plague is caused by the bacterium Yersinia pestis. A bubo is an inflamed and enlarged lymph node. After Yersinia pestis has entered the body, immune cells – macrophages – are attracted to the focus of infection. Macrophages ingest Yersinia pestis, but some bacteria survive and spread to the lymph nodes, where they multiply uncontrollably, causing inflammation.
Scientists examined the DNA of 516 Europeans who died shortly before, during, and shortly after the Black Death in London and across Denmark. The DNA of the survivors of the epidemic and their descendants was different from the DNA of those who died from the plague. The ERAP2 gene differed the most. In plague victims, the ERAP2 gene encoded a truncated protein variant involved in the innate immune response and antigen presentation, while in survivors, it was a full-length variant with higher activity.
The full-length ERAP2 protein variant presents a more diverse array of Yersinia pestis-associated antigens and increases T-killers’ activity, contributing to protection against plague. Macrophages with a full-length version of the ERAP2 protein more effectively inhibit the intracellular replication of the plague bacillus. In addition, protection against the plague bacillus is associated with a five-fold increase in ERAP2 expression in cells.
People with a full-length ERAP2 protein and its increased expression were 40% more likely to survive the Black Death. Full-length ERAP2 was associated with a more remarkable ability to inhibit the spread of the plague bacillus and lower levels of pro-inflammatory cytokines, which reduced tissue damage.
However, for modern people, the full-length ERAP2 protein can play not only a protective but also a detrimental role. So, ERAP2 increases the risk of autoimmune diseases, including Crohn’s disease and juvenile idiopathic arthritis.
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Reference
Evolution of immune genes is associated with the Black Death
