Scientists have 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 some autoimmune diseases.
The study of centuries-old DNA from victims and survivors of the bubonic plague that occurred in the 14th century found that people with what the scientists describe as a “good” variant of a particular gene, known as ERAP2, survived at much higher rates.
The findings, which are published in the journal Nature, shed light on how the Black Death – which wiped out about 50% of the European population – shaped the evolution of immunity genes such as ERAP2, setting the course for how humans respond to disease today.
The “selectively advantageous” ERAP2 variant is also a known risk factor for Crohn’s disease and has been associated with other autoimmune diseases, the researchers noted.
Luis Barreiro, professor of genetic medicine at the University of Chicago Medical Center in the US and co-senior author of the study, said: “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.”
For the study, more than 500 ancient DNA samples were extracted from the remains of individuals, including those buried in London’s East Smithfield plague pits, which were used for mass burials in 1348 and 1349. The samples came from people who had either died before the plague, died from it or survived the Black Death.
Signs of any genetic adaptation related to the plague, which is caused by the bacterium Yersinia pestis, were then looked for. Having two copies of the “good” ERAP2 gene was found to have allowed individuals to produce functional proteins – molecules which help the immune system recognise an infection.
These ERAP2 copies allowed for “more efficient neutralisation of Y pestis by immune cells”, according to the scientists from McMaster University, the University of Chicago, the Pasteur Institute and other organisations.
The presence of the variant would have made a person about 40% more likely to survive the Black Death than those who did not have it.
Hendrik Poinar, professor of anthropology at McMaster University in Canada and co-senior author on the study, said the research was the first study of how pandemics could modify genomes but go undetected in modern populations.
“These genes are underbalancing selection – what provided tremendous protection during hundreds of years of plague epidemics has turned out to be autoimmune-related now,” he added.
“A hyperactive immune system may have been great in the past but in the environment today it might not be as helpful.”
