A new study published today shows how a single pathogen or survivors of the Black Death pandemic can have such a strong impact on the evolution of the immune system.

Infectious diseases are a major force in human evolution, and a pandemic has the potential to dramatically alter the immune response genes.

An international team of researchers looked at the DNA of people who died and people who lived during the Black Death pandemic. They found that there were key genetic differences that determined who lived and who died, as well as how those parts of our immune systems have changed since then.

McMaster University, the University of Chicago, the Pasteur Institute, and other institutes uncovered genes that protected individuals against the bubonic plague outbreak 700 years ago. 

Their research was just released today in the peer-reviewed journal Nature.

According to the study’s authors, genes that formerly provided resistance to the Black Death are now linked to an increased risk of developing autoimmune disorders including Crohn’s disease and rheumatoid arthritis.

The team looked at a 100-year period before, during, and after the Black Death, which hit London in the mid-1300s. It killed more than 50% of the population in some of the densestly populated regions of the planet at the time, making it the single-worst human mortality event in recorded history.

More than 500 old DNA samples were taken from the bodies of people who died before the Black Death, died from it, or lived through it in London. Some of these people were buried in the East Smithfield plague pits, which were used for mass burials in 1348 and 1349. Samples from the bones buried in five different places around Denmark were also collected.

Scientists looked for indicators of genetic adaptability in plague-causing Yersinia pestis.

They found four genes that were being selected, and all of them make proteins that protect our bodies from pathogens. They also found that different versions of these genes, called alleles, either protected or made a person vulnerable to plague.

People with two identical copies of a gene called ERAP2 were much more likely to survive the pandemic than those with the opposite set of copies. This is because the “good” copies made it easier for immune cells to fight off Y. pestis.

“When a pandemic of this nature – killing 30 to 50 per cent of the population – occurs,” explains evolutionary geneticist and author of the paper Hendrik Poinar, “there is bound to be selection for protective alleles in humans, which is to say people susceptible to the circulating pathogen will succumb. Even a slight advantage means the difference between surviving or passing. Of course, those survivors who are of breeding age will pass on their genes.”

At the start of the Black Death, people in Europe were very vulnerable because they hadn’t been around Yersinia pestis in a long time. As waves of the pandemic happened over the next few hundred years, the death rate went down.

According to research, those who had the protective allele for the ERAP2 gene (the healthy copy of the gene, or characteristic), had a 40–50%– higher chance of surviving than those who did not.

According to human geneticist and University of Chicago professor of genetic medicine Luis Barreiro, “the selective advantage associated with the selected loci are among the strongest ever reported in humans showing how a single pathogen can have such a strong impact on the evolution of the immune system.”

According to the research team, throughout time, our immune systems have changed how they react to pathogens, to the point that a gene that in the Middle Ages protected against plague is now linked to a higher risk of developing autoimmune illnesses. This is the delicate balancing act that evolution has performed with our genome.

According to Javier Pizarro-Cerda, head of the Yersinia Research Unit and director of the World Health Organization Collaborating Centre for Plague at the Pasteur Institute, “This highly original work has only been possible only through a successful collaboration between very complementary teams working on ancient DNA, on human population genetics, and the interaction between live, virulent Yersinia pestis and immune cells.”

“Understanding the dynamics that have shaped the human immune system is key to understanding how past pandemics, like the plague, contribute to our susceptibility to disease in modern times,” adds Poinar.

Source: 10.1038/s41586-022-05349-x

Image Credit: Matt Clarke/McMaster University

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