Genes That Helped People Survive the Plague Linked to Autoimmune Disorders in Descendants

Scientists have discovered that the same genetic characteristics that helped people survive the Black Death more than 700 years ago are now linked to an elevated risk of developing certain autoimmune disorders.

Using the DNA of victims and survivors of the Black Death from the 14th century, scientists have discovered that Europeans with a variation of the gene called ERAP2 had a substantially better chance of surviving the disease. The mutations provided protection against the Black Death pathogen Yersinia pestis, which went on to kill off nearly half of Europe’s population.

These results, published in the Journal “Nature,” provide insight into how the Black Death influenced the development of immunity genes like ERAP2 and laid the groundwork for how some people react to disease today. For instance, inheritors of the gene have a higher risk for autoimmune diseases such as Crohn’s disease and arthritis.

Luis Barreiro, professor of genetic medicine at the University of Chicago Medical Center and co-author of the study, believes this study provides new insight into the true evolutionary impact of the plague.

“This is, to my knowledge, the first demonstration that indeed, the Black Death was an important selective pressure to the evolution of the human immune system.”

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The study was carried out on more than 500 ancient DNA samples collected from the teeth of people who had died before, during or after the plague. Some samples were taken from skeletons buried in London’s East Smithfield plague pits. According to Barreiro, the pits were used for mass burials in 1348 and 1349 when people were dying so quickly that the city’s cemeteries were running out of space.

“So the king [Edward III], at the time, bought this piece of land and started digging it. There’s basically layers and layers of bodies one on top of each other.”

Samples that contained two copies of the ERAP2 gene indicated an ability to produce functional proteins, which helped the immune system to recognize an infection. The variant also helped immune cells neutralize the virus more efficiently, making the person 40% more likely to survive the plague than their peers. However, the mutations enhanced the body’s inflammatory response, making people more susceptible to autoimmune disorders.

Hendrik Poinar, professor of anthropology at McMaster University in Canada and co-senior author of the study, said the study showed the ability of pandemics to alter genome sequences in the long-term without being detected in modern populations.

“These genes are under balancing selection – what provided tremendous protection during hundreds of years of plague epidemics has turned out to be autoimmune-related now. A hyperactive immune system may have been great in the past, but in the environment today, it might not be as helpful.”

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Evolutionary biologist David Enard from the University of Arizona said the speed of the adaptation over just a few decades had other implications. The 40% survival advantage the variant bestowed is the most significant evolutionary advantage recorded in humans.

“The evolution is faster and stronger than anything we’ve seen before in the human genome. It’s really a big deal. It shows what’s possible [for humans], in terms of adaptation in response to many different pathogens.”

According to paleogeneticist Maria Avila Arcos, the study still has its limitations by only being carried out on a narrow population. The plague also affected parts of Asia and North Africa.

“There might be way more cellular mechanisms people used to cope with this devastating outbreak, but we’re just seeing the mechanisms shared across the English and Danish.”