The Black Death affected the body’s immune system so much that it still affects the way our bodies respond to today’s disease, a study has found.
By analyzing centuries of DNA from victims and survivors of a devastating pandemic, which is estimated to have killed more than 200 million people between 1346 and 1353, scientists have identified the key to determining who lives and who dies genetic differences.
These aspects of our immune system are constantly evolving, and genes that once helped prevent the Black Death, the deadliest plague in human history, are now associated with susceptibility to diseases like rheumatoid arthritis and Crohn’s disease.
The researchers examined more than 500 DNA samples from victims and survivors – mostly in London – spanning 100-year windows before, during and after the pandemic.
These include those buried in the capital’s East Smithfield Plague Pit in 1348 and 1349, which were used for mass burials similar to those seen in some of the countries worst hit by COVID-19.
“This is a very straightforward way to assess the evolutionary impact of a single pathogen on humans,” said study co-senior author Dr. Luis Barreiro.
The geneticist added: “To my knowledge, this is the first demonstration that the Black Death was an important selection pressure on the evolution of the human immune system.”
How is the research conducted?
Scientists from McMaster University, the University of Chicago, the Pasteur Institute and other institutions looked for signs of genetic adaptations linked to the plague.
They identified four genes under selection, all involved in the production of proteins that protect our systems from invading pathogens.
Versions of these genes, called alleles, either protect or make a person susceptible to the plague.
Those with two identical copies of a particular gene, ERAP2, had much higher survival rates than those with opposite copies because they neutralized bacteria more efficiently.
What do these genes mean for mortality?
The bacterium that caused the plague, called Yersinia pestis, was new and most vulnerable when it arrived in Europe.
It kills more than 50 percent of the people who live in some of the most densely populated areas in the world.
In future waves over the ensuing centuries, as the immune system gets used to dealing with the disease, the death rate declines — as we’re starting to see with COVID-19.
Those with the same copy of ERAP2 were 40-50% more likely to survive, the researchers said.
So why is this important for the current disease?
The effects of the Black Death were so great that it shaped the very nature of the human immune system – if it didn’t adapt, more people would die.
But the seven-year study found that genes that were once protective against plague in the Middle Ages are now associated with increased susceptibility to autoimmune diseases.
The team describes it as a balancing act between evolution and the human genome.
“Diseases and epidemics like the Black Death can have an impact on our genome, just like an archaeological project to test,” explained senior co-author Professor Hendrik Bonnard
“This is the first study of how epidemics alter our genomes but go undetected in modern populations.
“These genes are unbalanced selection – genes that provided great protection during centuries-old plague epidemics are now shown to be associated with autoimmunity. An overactive immune system may have been fine in the past, but may not be in today’s environment Just as helpful.”
The full study results have been published in the journal Nature.
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