The Black Death could be the reason why we suffer from other diseases today.

The Black Death -the most devastating event in history – not only wiped out half of Europe’s population in less than five years, it also modified our genome and our immune system.. But it did so in a way that, to this day, may cause the descendants of the survivors of the medieval epidemic to be at increased risk for autoimmune diseases.

According to a study published in the journal Nature, the same genes that once protected certain people against the Black Death are today associated with an increased susceptibility to autoimmune pathologies. There is a long list of autoimmune diseasesamong them are the psoriasis, Crohn’s disease, rheumatoid arthritis, multiple sclerosis and celiac disease.

Research

The authors of the study, conducted by the University of Chicago (United States), McMaster University (Canada) and the Pasteur Institute (France), have studied the. genetic impact of bubonic plague which 700 years ago wiped out between 30% and 60% of the population of North Africa, Europe and Asia.

There has long been speculation that the pandemic of Black Death, caused by the Yersinia pestis bacteriumcould have exerted an important selective pressure on humans but it was difficult to demonstrate by studying modern populations because, since then, humans have faced many selective pressures.

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For this study, the team sequenced ancient DNA samples from bones of more than 200 individuals from London and Denmark who died before, during and after the passage of the Black Death in the late 1340s. From 300 genes related to immunity, they selected four that, depending on the variant, protected or increased susceptibility to Y. pestis.

The team focused on. a gene with a particularly strong association with susceptibility: ERAP2which contributes to the immune system’s recognition of the presence of an infection. Individuals who possessed two copies of a genetic variant specific genetic variant, called rs2549794were able to produce full-length copies of the ERAP2 transcript, and produced more of the functional protein.

“When a macrophage encounters a bacterium, it chops it into pieces to present to other immune cells signaling that there is an infection. So having the functional version of the gene, probably Improves our immune system’s ability to detect the invading pathogen.“, he explains Luis Barreiroof the University of Chicago and co-author of the study.

“According to our estimates, having two copies of the rs2549794 variant would have caused a person to have an 40% more likely to survive the plague than those with two copies of the nonfunctional variant,” he notes.

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Later, in the laboratory, the team showed that the rs2549794 variant affected the ability of living human cells to help fight plague, and that macrophages expressing two copies of the variant were more efficient neutralizing Yersinia pestis than those that did not.

“These results support the ancient DNA evidence that. rs2549794 is protective against plague”, according to Javier Pizarro-Cerdaof the Pasteur Institute.

More susceptible to develop autoimmune diseases.

But, over time, our immune system has evolved to respond to pathogens, and what used to be a protective gene against plague is now associated with a increased susceptibility to autoimmune diseases.. It is the balancing act with which evolution plays with our genome, the authors note.

This study is a first approximation of how pandemics can modify our genomes and go unnoticed in modern populations.

Upcoming research will expand the project to examine the entire genome, not just a set of genes related to immunity.

“Understanding the dynamics that have shaped the human immune system is key to understanding how we pandemics of the pastsuch as the plague, contribute to our susceptibility to disease today,” he concludes Hendrik Poinarof McMaster University and co-lead author of the study.

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