Monday, November 28

The black plague produced changes in our immune system that still persist

The black plague, caused by the bacteria Yersinia pestis, spread across Europe, the Middle East and North Africa between 1346 and 1350 and caused the death of between 30% and 50% of the population of the time. In the outbreaks of the following 400 years, mortality rates decreased. This could be due to a human genetic adaptation to the bacterium, as the authors of a study published this week in Nature.

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The work, which has been led by the University of Chicago (USA), has found evidence that one of the darkest periods in history exerted significant selective pressure on the population and produced changes in the human immune system that persist today. day.

As Luis Barreiro, professor of Genetic Medicine at the US university and co-author of the study, told SINC, “the Black Death was the greatest mortality event in history; therefore, we set out to test the hypothesis that people who survived this pandemic had genetic variants that increased their protection against Y. pestis”.

In addition to the University of Chicago, researchers from McMaster University (Canada) and the Pasteur Institute (France) have participated in the work.

Analysis of ancient DNA from the bones of more than 200 individuals

To explore the evolution of genetic variation in genes related to the immune system, scientists examined samples of ancient DNA from the bones of more than 200 individuals from London and Denmark who died before, during and after the plague wiped out the plague. 50% of the European population in the late 1340s.

By selectively sequencing a set of 300 immunity-related genes, they identified four genes that, depending on the variant, protected or increased susceptibility to Y. pestis.

Specifically, the team found that having two copies of a specific variant of the ERAP2 gene was strongly associated with survival of plague. Those who survived the pandemic passed on this functional genetic variant, called rs2549794, to their offspring.

“When a macrophage encounters a bacterium, it cuts it into pieces to present them to other immune cells signaling that there is an infection”, explains Barreiro. “Having the working version of the gene seems to create an advantage, probably by improving our immune system’s ability to detect the invading pathogen. According to our estimates, possessing two copies of the rs2549794 variant would have made a person 40% more likely to survive the Black Death than those with two copies of the non-functional variant.”

An advantage at a cost to offspring

However, this advantage that made these people survive the pandemic, in turn, entails a cost: “Having that same variant that we found to be protective against the Black Death is today associated with greater susceptibility to certain autoimmune diseases, such as it could be Chrohn’s disease,” warns Barreiro.

The researcher points out that this work has evaluated “in a very direct way the impact that a single pathogen had on human evolution. It has long been speculated that the Black Death may have been a strong cause of selection, but this is difficult to prove when looking at modern populations, because humans have had to contend with many other selective pressures. The only way to address the issue was to reduce the time window analyzed”, he emphasizes.

“As far as I know,” he adds, “this is the first demonstration that, indeed, the Black Death was an important selective pressure for the evolution of the human immune system.”

Co-author Hendrik Poinar, Professor of Anthropology at McMaster University, said: “What provided enormous protection during hundreds of years of plague epidemics has turned out to be linked to autoimmunity now. An overactive immune system may have been great in the past, but in today’s environment it might not be as helpful.”

The authors plan to expand the project to examine the entire genome, not just a select set of immunity-related genes. Their next goal is to analyze the genetic variants that affect susceptibility to bacteria in modern humans, and compare them with ancient DNA to determine whether those variants were also the result of natural selection.

“There’s a lot of talk about how pathogens have shaped human evolution, so being able to formally show which pathways and genes have been targeted for selection really helps us understand what has allowed humans to adapt and exist today.” says Barreiro, who concludes: “This tells us about the mechanisms that allowed us to survive throughout history and why we are still here today.”