The Black Death impacted human genetics so significantly that the Middle Age pandemic still affects our health more than 700 years later.
An international team of researchers examined DNA from victims and survivors of the bubonic plague - also known simply as 'the plague' - that occurred in the 14th century, wiping out around 50% of the European population.
Genes that offered protection against the bubonic plague are associated with an increased susceptibility to autoimmune diseases such as Crohn's and rheumatoid arthritis today, according to DNA analysis.
They found that individuals who had what the scientists describe as a "good" variant of a particular gene, known as ERAP2, survived the pandemic at much higher rates than those who did not.
The researchers said their findings, published in the journal Nature, shed light on how the Black Death shaped the evolution of immunity genes such as ERAP2, setting the course for how humans respond to disease today.
Luis Barreiro, professor of genetic medicine at the University of Chicago Medical Center in the US and co-senior author on 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."
One of the worst plagues in history, the Black Death arrived on the shores of Europe in 1347.
Five years later, around 25 to 50 million people were dead across the continent.
The first outbreak of plague swept across England in 1348, ravaging London and East Anglia before spreading to Wales and the Midlands.
For the study, the scientists extracted more than 500 ancient DNA samples from the remains of individuals, including those buried in London – in the East Smithfield plague pits 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.
The researchers then searched for signs of any genetic adaptation related to the plague, which is caused by the bacterium Yersinia pestis.
The team found that having two copies of the "good" ERAP2 gene allowed the individuals to produce functional proteins – molecules which help the immune system recognise an infection.
According to the scientists, these ERAP2 copies allowed for "more efficient neutralisation of Y. pestis by immune cells".
Prof Barreiro said the presence of this variant would have made a person about 40% more likely to survive the Black Death, compared with those who did not have it.
It meant those who survived the Black Death were able to pass on this "good" ERAP2 gene variant to their children.
Further analysis revealed that while ERAP2 is protective against the Black Death, in modern populations, it is associated with an increased susceptibility to autoimmune diseases, such as Crohn's disease and rheumatoid arthritis.
Hendrik Poinar, professor of anthropology at McMaster University in Canada and co-senior author on the study, said: "This is a first look at how pandemics can modify our genomes but go undetected in modern populations.
"These genes are under balancing selection – what provided tremendous protection during hundreds of years of plague epidemics has turned out to be autoimmune related now.
"A hyperactive immune system may have been great in the past but in the environment today it might not be as helpful."
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