An international team of researchers has identified genetic traits that determined who survived the Black Death more than 700 years ago, but which are today associated with an increased susceptibility to autoimmune diseases such as Crohn’s disease and rheumatoid arthritis.
The study, published in the journal Nature, involved the extraction and screening of more than 500 ancient DNA samples from the remains of individuals who had died in the 100-year window before, during and after the Black Death. This included those buried in London’s East Smithfield plague pits, which were used for mass burials in 1348 and 1349.
Signs of any genetic adaptation related to the plague, which is caused by the bacterium Yersinia pestis (Y pestis), were then looked for.
Four genes were identified by the researchers, all of which are involved in the production of proteins that defend our systems from invading pathogens, and found that alleles of those genes either protected or rendered the individual susceptible to plague.
The researchers found that individuals with two identical copies of the ERAP2 gene survived the Black Death at a much higher rate than those with the opposing set of copies, because these ‘good’ copies allowed for more efficient neutralisation of Y pestis by immune cells.
Researchers estimate that people with the ERAP2 protective allele were 40% to 50% more likely to survive than those who did not.
Europeans living at the time of the Black Death were initially very vulnerable because they had had no recent exposure to Y pestis, but as waves of the pandemic occurred repeatedly over the following centuries, mortality rates decreased.
The team reports that over time our immune systems have evolved to respond in different ways to pathogens, to the point that what had once been a protective gene against plague in the Middle Ages is today associated with increased susceptibility to autoimmune diseases.
‘Our results highlight the contribution of natural selection to present-day susceptibility towards chronic inflammatory and autoimmune disease,’ the team outlined in the study.
‘Consistent with this hypothesis, the selectively advantageous ERAP2 variant is also a known risk factor for Crohn’s disease, and ERAP2 variation has also been associated with other infectious diseases.
‘Likewise, another of our top candidate loci is associated with an increased risk of rheumatoid arthritis and systemic lupus erythematosus, such that retaining the putatively advantageous allele during the Black Death confers increased risk for autoimmune disease in present-day populations.’