How did the plague evolve? 5,500-year-old DNA suggests much older origin

The plague terrorizes humans for millennia: In the 1300s, the Black Death unleashed the deadliest pandemic in human history, killing up to half of the European population. Long before that, around 540 CE, the “Justinian” plague destabilized the Roman Empire, and some researchers claim this may have precipitated the collapse of the empire. But when and where the plague first appeared has long remained a mystery. Now a new study published today in Nature claims to have identified fatal cases of plague among hunter-gatherers dating back around 5,500 years. This epidemic constitutes the first known case of plague in the history of humanity.

The results reveal a new feature of ancient plague epidemics: They did not need densely populated communities to occur, says Roman Wölfel, director of the Bundeswehr Institute of Microbiology in Germany, who was not involved in the new study.

“This study is exciting because it pushes deadly plague outbreaks further back in time and into a very different social context than we often imagine,” he says. “The striking point is that these were not dense urban or agricultural populations but small hunter-gatherer communities, and yet the plague still appears to have caused severe, clustered mortality. »

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Researchers analyzed the remains of dozens of hunter-gatherers buried in cemeteries near Lake Baikal, in what is now Siberia, during the mid-Holocene, a period that spanned about 7,000 to 5,000 years ago. Genetic data revealed that many people were infected with Yersinia pestis the bacteria that causes the plague. They found that many members of the same family were infected, suggesting human-to-human transmission. Children aged eight to 11 were particularly likely to die from this scourge.

“This is the first time we have seen direct evidence of mass mortality and plague outbreaks in prehistoric hunter-gatherer societies,” Ruairidh Macleod, lead author of the paper and a postdoctoral researcher at the University of Oxford, said at a press briefing on Tuesday.

Y. pestis has already been detected in ancient tombs, including in agricultural communities that existed around 5,000 years ago. But until now, there was no clear evidence that the oldest strains were deadly.

The results shed new light on the evolution of Y. pestis, a pathogen that “has played an extremely important role in human history” and is still circulating today, noted environmental geneticist Eske Willerslev, lead author of the paper and professor at the University of Copenhagen and the University of Cambridge, at the same press conference. Today, the bacteria is not as deadly as before – largely thanks to antibiotics but also because of changes in its genome.

“Ancient bacterial genomes are a kind of evolutionary archive. They show us when pathogens acquired characteristics that made them more transmissible, more virulent or better adapted to particular hosts or vectors,” explains Wölfel.

“For the plague, it is important today because Yersinia pestis is not just a historical pathogen. It still persists in animal reservoirs and can spread to humans,” he adds. “Understanding how plague spread between animals and humans in the past helps us think about the current zoonotic risk.”

Understanding how this bacteria evolved could help scientists better prepare for future outbreaks, Willerslev said. Part of what made Y. pestis so deadly during the Black Death, for example, was a mutation in bacteria this allowed it to survive in fleas and jump to humans via flea-infested rats.

Y. pestis samples older than about 3,800 years do not have this mutation, suggesting that the 5,000-year-old strains were probably not spread by fleas. In the new study, researchers hypothesize that the bacteria may have been transmitted to humans from marmots, a type of ground squirrel, whose remains have also been found in Siberian burial sites.

What remains uncertain is the extent of these ancient animal reservoirs of plague, Wölfel says. “For future work, the big question is not only when the plague appeared, but also how it spread between animals, landscapes and people,” he adds.

Ultimately, the paper provides another source of information for understanding how dangerous bacteria emerge, evolve and spread over time, he says.

“Plague is often treated as a disease of the past, but this article shows why its evolutionary history remains relevant to public health and biosecurity today,” says Wölfel. “It is still an ecological disease, sustained in animal reservoirs, and that makes its past directly relevant to how we assess risk today.” »