Key genetic distinctions that decided who survived and who perished during the Black Death epidemic have been uncovered by an international team of scientists who examined centuries-old DNA from victims and survivors. They have also shown how those immune system components have changed over time.
Researchers from McMaster University, the University of Chicago, the Pasteur Institute, and other institutions examined and discovered genes that gave some people resistance to the terrible bubonic plague pandemic that ravaged Europe, Asia, and Africa approximately 700 years ago. Their study has been published today (October 19, 2022) in the journal Nature.
According to the researchers, the same genes that once provided immunity from the Black Death are now linked to a higher risk of developing autoimmune disorders including Crohn’s and rheumatoid arthritis.
The group concentrated on the 100 years before, during, and after the Black Death, which arrived in London in the middle of the fourteenth century. It killed more than 50% of the population in some of the densestly populated regions of the world at the time, making it the single-worst human mortality event in recorded history.
From the bones of people who had died before the plague, contracted it, or survived the Black Death in London, including those buried in the East Smithfield plague pits used for mass graves in 1348–1349, more than 500 ancient DNA samples were extracted and processed. Samples from the bones buried in five different places around Denmark were also collected.
The bacteria Yersinia pestis, which causes the plague, was the focus of researchers looking for genetic adaptations.
Four genes that are involved in producing proteins that protect our systems from invasive pathogens were found to be under selection. They discovered that different alleles of these genes can either protect one from plague or make one susceptible to it.
Because the ‘good’ copies made it possible for immune cells to more effectively neutralize Y. pestis, people with two identical copies of a specific gene, known as ERAP2, fared better in the pandemic than people with the opposing set of copies.
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 to the evolution of the immune system.
Luis Barreiro
“When a pandemic of this nature killing 30 to 50 percent of the population occurs, 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,” explains evolutionary geneticist Hendrik Poinar, an author of the Nature paper, director of McMaster’s Ancient DNA Centre, and a principal investigator with the Michael G. DeGroote Institute for Infectious Disease Research and McMaster’s Global Nexus for Pandemics & Biological Threats.
Due to the fact that they had not recently been exposed to Yersinia pestis, Europeans living during the time of the Black Death were at first extremely vulnerable. Mortality rates fell as the epidemic recurred repeatedly throughout the ensuing centuries.
Researchers estimate that people with the ERAP2 protective allele (the good copy of the gene, or trait), were 40 to 50 percent more likely to survive than those who did not.
“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 to the evolution of the immune system,” says human geneticist Luis Barreiro, an author on the paper, and professor in Genetic Medicine at the University of Chicago.
According to the research team, over time, our immune systems have changed how they react to pathogens, to the point where a gene that in the Middle Ages protected against plague is now linked to a higher risk of developing autoimmune diseases. This is the delicate balancing act that evolution has performed with our genome.
“This highly original work has 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,” says Javier Pizarro-Cerda, head of the Yersinia Research Unit and director of the World Health Organization Collaborating Centre for Plague at the Pasteur Institute.
“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,” says Poinar.
The findings, the result of seven years of work from graduate student Jennifer Klunk, formally of McMaster’s Ancient DNA Centre, and postdoctoral fellow Tauras Vigylas, from the University of Chicago, allowed for an unprecedented look at the immune genes of victims of the Black Death.
The research was funded in part by the Social Sciences and Humanities Research Council of Canada (SSHRC), The National Institutes of Health (NIH), and the Canadian Institute for Advanced Research, under the Humans and the Microbiome program.
