A gene that protected us from the black plague makes us more prone to autoimmune diseases

Researchers take DNA samples from individuals buried in London's East Smithfield Cemetery in 1348 and 1349. / Archeology Museum London

Science | Genetics

They identify the DNA variant that made the difference between surviving and dying during the great pandemic of the 14th century

A gene that protected us against the Black Death almost 700 years ago makes us more prone to autoimmune diseases such as Crohn's and rheumatoid arthritis, says an international team of researchers in the journal Nature. The study's authors have identified the genetic differences that determined who lived and who didn't when the Black Death swept through Europe in the Middle Ages, and discovered that this led to the spread of a beneficial genetic variant then, but not today.

Caused by the 'Yersinia pestis' bacterium, the Black Death swept across Europe and North Africa in the 14th century. The pandemic peaked between 1347 and 1353. It is estimated that it killed between 75 and 200 million people. Only in Europe, to more than 50% of the population in less than five years. A team of researchers led by the Portuguese geneticist Luis Barreiro, from the University of Chicago, has now seen the changes that the disease caused in our genome.

“It has long been speculated that the Black Death could be a strong cause of selection (in our genome), but it is difficult to prove this when looking at modern populations, because humans have had to deal with many other selective pressures since then. . The only way to address the issue is to reduce the time window that we analyze”, explained Barreiro.

He and his collaborators narrowed that window down to just 100 years by analyzing DNA samples from bones from 206 individuals from London and Denmark who died before, during and after the pandemic. Thus, they discovered in some subjects a variant of ERAP2, a key gene to help the immune system detect an infection, called rs2549794.

A researcher from Barreiro's lab works with human cell cultures. /

University of Chicago

They infected with 'Y. pestis' human cell cultures and found that macrophages – cells specialized in the detection and destruction of pathogens – with two copies of this variant of ERAP2 were more efficient at neutralizing plague bacteria than those without it. The authors calculate that people with two copies of rs2549794 were 40% to 50% more likely to survive the disease and thus pass on the protective gene to their offspring.

rapid expansion

“When a pandemic of this nature occurs – which kills between 30% and 50% of the population – it is inevitable that there will be a selection of protective alleles (gene variants) in humans, that is, that people susceptible to the pathogen succumb. Even a slight advantage means the difference between surviving or dying. Of course, survivors who are of reproductive age will pass on their genes," explains evolutionary geneticist Hendrik Poinar of McMaster University, Canada, and co-author of the study.

The high mortality of the first wave of plague was due to the fact that our ancestors had not been exposed to the bacteria in centuries. Until then, the last known pandemic associated with 'Y. pestis' had been the so-called plague of Justinian (541-549), in which between 25 and 50 million people died. When the waves of plague followed each other in Europe from 1347, the rapid expansion of the protective genetic variant –because those who carried it were more likely to survive– meant that mortality was increasingly lower.

But what was beneficial against the plague for now is less so. The same ERAP2 variant that protected our ancestors from the Black Death makes us more prone to autoimmune diseases today. "An overactive immune system may have been great in the past, but in today's environment it may not be as useful," says Poinar, for whom "understanding the dynamics that have shaped the human immune system is key to understanding how pandemics of the past, like the plague, contribute to our susceptibility to disease today.