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The Black Death, the world’s most devastating plague outbreak, killed half the population of medieval Europe in the span of seven years in the 14th century, altering the course of human history.
But what about the survivors of what remains the greatest death event on record? A new study published Wednesday in the journal Nature suggests that more than luck determined who lived and who died.
Analysis of centuries-old DNA from victims and survivors of the Black Death 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 conferred protection against plague now linked to greater susceptibility to autoimmune diseases such as Crohn’s disease and rheumatoid arthritis, according to the report. ‘study.
“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 inform the mechanisms and genetic determinants current susceptibility to the disease,” study co-author Luis Barreiro, professor of genetic medicine at the University of Chicago, said by email.
The seven-year study involved the extraction of isolated DNA from three different groups of skeletal remains discovered in London and Denmark: the plague victims, those who died before the Black Death and those who died between 10 and 100 years after the plague struck.
More than 300 samples came from London, a city particularly affected by the plague, including individuals buried in the East Smithfield plague pits used for mass burials at the height of the epidemic in 1348-1349. Another 198 samples were taken from human remains buried in five locations in Denmark.
DNA was extracted from the dentin in the roots of individuals’ teeth, and the researchers were also able to check for the presence of Yersinia pestis, the bacterium that causes plague. They then looked for signs of genetic adaptation to the disease.
“It’s a LONG process, but at the end you have the sequence of these genes for these people from before, during and after the plague and you can ask: were the genes carried by one population different from those in ‘another population,’ co-author Hendrik Poinar, a professor of anthropology at McMaster University in Hamilton, Ont., said in an email.
The team identified a variant of a particular gene, known as ERAP 2, which seemed to have a strong association with the plague. Before the Black Death, the variant of ERAP2 considered protective of the plague was found in 40% of the individuals included in the London study. After the Black Death, it was 50%. In Denmark, the disparity in percentiles was more marked – from about 45% of samples buried before the plague to 70% buried after.
The team is not yet sure why this variant conferred protection, but their lab experiments on cultured cells indicated that in people with the ERAP 2 variant, an immune cell known as a macrophage caused a very different response to Yersinia pestis, Barreiro explained. . Macrophages from individuals carrying the variant were better able to kill bacteria in laboratory experiments than macrophages from individuals who lacked it.
“We don’t know if it still protects against plague given that the number of cases in current populations is very low, but we hypothesized that it should,” he said. It is also presumably the variant is beneficial against other pathogens – although this is not part of the research.
The downside of the variant is that it has been linked to a greater susceptibility to autoimmune diseases, such as Crohn’s disease, where the immune system becomes overactive.
“This suggests that the people who survived the Black Death paid one prize, which is having an immune system that increases our susceptibility to reacting against ourselves,” Barreiro said.
He said the Covid-19 outbreak was unlikely to shape our immune systems in the same way – largely because the disease predominated kills people past their childbearing age, meaning genes that confer protection are unlikely to be passed on to the next generation.
This change in human genetic make-up occurring within decades is also a rare example of rapid natural selection, said David Enard, a professor in the Department of Ecology and Evolutionary Biology at the University of Arizona, who did not participated in 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 authors to precisely date natural selection”.
“Although evolutionary biologists had previously wondered about the possibility of natural selection during the Black Death, proper investigation was not possible without this precise dating of many samples.”
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