Black Death May Have Shaped Human Immune System

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Considered the most devastating pandemic in history, the Black Death left a biological legacy that is still present today. According to a study published this Wednesday (19), the disease caused a change in the genome and in the immune system that affects the current population.

Scientists have discovered that the same genes that once protected the population against the Black Death are now associated with increased susceptibility to autoimmune diseases such as Crohn’s disease, lupus and rheumatoid arthritis. In these illnesses, the system that defends against disease and infection attacks the body’s own healthy tissue.

“Our genome today is a reflection of the entire history of our evolution,” said Luis Barreiro, from the University of Chicago and co-author of the study, which also involved researchers from McMaster University, in Canada, and the Pasteur Institute, in France.

The Black Death, also known as the bubonic plague, wiped out half the European population in less than five years. Between 1347 and 1351, the disease, which would have been caused by the bacterium Yersinia pestis found in rats, left 75 million to 200 million dead in Eurasia. It was the first major European plague outbreak and the disease’s second pandemic, creating a series of religious, social and economic upheavals with profound effects on the course of European history.

To study the impact of the Black Death, researchers analyzed DNA samples from bones from more than 200 individuals from London and Denmark who died over 100 years spanning the period before, during and after the Black Death pandemic, at the end from the 1340s.

The researchers identified four genes that, depending on the variant, protect or increase susceptibility to the bacteria that causes the bubonic plague. According to the study, published in the specialized journal Nature, what helped the population in the Middle Ages caused problems for later generations, by increasing the frequency of harmful mutations in modern times.

“A hyperactive immune system may have been great in the past, but in today’s environment it may not be as useful,” said Hendrik Poinar, co-author of the study. “Understanding the dynamics that shaped our immune system is key to understanding how past pandemics like the plague contribute to our susceptibility to current diseases,” he added.

unpublished study

The researchers focused the study on a gene with a particularly strong association with susceptibility: ERAP2, which helps the immune system recognize the presence of an infection. Individuals who had two copies of a specific genetic variant, designated rs2549794, were able to produce full copies of the ERAP2 transcript and produced more functional protein.

According to the study, the rs2549794 variant affected the ability of human cells to help fight the plague and that macrophages that expressed two copies of the variant were more efficient at neutralizing the disease. Yersinia pestis. “These results support ancient DNA evidence that rs2549794 is protective against plague,” says Javier Pizarro-Cerda of the Pasteur Institute.

Over time, however, the immune system has evolved to respond to pathogens, and what was once a protective gene against plague is now associated with increased susceptibility to autoimmune diseases. It’s the balancing act with which evolution plays with the current human genome, the authors point out.

According to Barreiro, the study is unprecedented in being the first to demonstrate how the Black Death was important for the evolution of the human immune system. Future research intends to expand the project to analyze the entire genome, in addition to genes related to immunity.

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