(CNN) – The Black Death, the world’s most devastating plague outbreak, killed half the population of medieval Europe in seven years in the 14th century and changed the course of human history.
But what about the survivors of what remains the largest fatality event on record? New research was released on Wednesday in the journal Nature suggests that more than luck decided who lived and who died.
Analysis of centuries-old DNA from Black Death victims and survivors has identified key genetic differences that helped people survive the plague, according to a study published in the journal Nature.
These genetic differences continue to shape the human immune system today, with genes that once offered protection against the plague now being linked to greater susceptibility to autoimmune diseases such as Crohn’s disease and rheumatoid arthritis, the study found.
“We are the descendants of those who survived past pandemics… and understanding the evolutionary mechanisms that contributed to our survival is not only important from a scientific perspective, but can also shed light on the mechanisms and genetic determinants of disease susceptibility today.” said study co-author Luis Barreiro, a professor of genetic medicine at the University of Chicago, via email.
plague pit samples
The seven-year study involved the extraction of DNA isolated from three different groups of excavated skeletal remains in London and Denmark: plague victims, those who died before the Black Death and those who died between 10 and 100 years after the plague.
More than 300 samples came from London, a city particularly hard hit by the plague, including from individuals buried in the East Smithfield plague pits, which were used for mass burials at the height of the outbreak in 1348-1349 . A further 198 samples were taken from human remains buried at five locations in Denmark.
DNA was extracted from dentin in people’s tooth roots, and the researchers were also able to verify the presence of Yersinia pestis, the bacterium that causes plague. They then looked for signs of a genetic adaptation to the disease.
“It’s a LONG process, but at the end you have the sequence of these genes for these people before, during and after the plague and you can ask: Do the genes that one population carried look different than another population,” he said Co-author Hendrik Poinar, a professor of anthropology at McMaster University in Hamilton, Ontario, in an email.
The team nailed it a variant of a particular gene known as ERAP 2 that appeared to have a strong association with the plague. Before the Black Death, the variant of ERAP2 found to protect against the plague was found in 40% of the people involved in the London study. After the Black Death it was 50%. In Denmark, the percentage disparity was more pronounced – changing from about 45% of samples buried before the plague to 70% after.
The team doesn’t yet know exactly why this variant conferred protection, but their laboratory experiments using cultured cells showed that in people with the ERAP-2 variant, an immune cell known as a macrophage elicited a very different response to Yersinia pestis, Barreiro explained. Macrophages from people with the variant were better at killing the bacteria in laboratory experiments than macrophages from people who lacked it.
“We don’t know if it still protects against the plague given the very low number of cases in today’s population, but we have speculated that it should,” he said. It is also likely that the variant is beneficial against other pathogens – although this was not part of the research.
price of immunity
The downside of the variant is that it has been linked to a greater susceptibility to autoimmune diseases, such as Crohn’s disease, in which the immune system becomes overactive.
“This suggests that populations that survived the Black Death paid a price that is having an immune system that increases our susceptibility to reactions against ourselves,” Barreiro said.
He said it was unlikely that the outbreak of Covid-19 would shape our immune systems in a similar way – mainly because the disease was prevalent kills people past their reproductive age, meaning genes conferring protection are unlikely to be passed on to the next generation.
This shift in the human genome over decades is also a rare example of rapid natural selection, said David Enard, a professor in the University of Arizona’s Department of Ecology and Evolutionary Biology who was not involved with the research.
“The narrow time window from which the samples were taken and the large number of samples analyzed are selling points of the study,” he said in a commentary published alongside the study, “allowing the authors to accurately date natural selection.”
“Although evolutionary biologists had previously pondered the possibility of natural selection during the Black Death, proper study was not possible without this accurate dating of many samples.”
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