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Ancient Yersinia Pestis Shows No Link to Neolithic Population Decline

NEW YORK – A team from Kiel University and other centers in Germany has reconstructed the genome of a 5,000-year-old Yersinia pestis strain, the oldest sequence so far for the plague-linked pathogen.

"What's so surprising is that we see already in this early strain more or less the complete genetic set of Y. pestis, and only a few genes are lacking," senior author Ben Krause-Kyora, a clinical molecular biology researcher at Christian-Albrecht University of Kiel and head of the university's Ancient DNA Lab, said in a statement. "But even a small shift in genetic settings can have a dramatic influence on virulence."

For a study appearing in Cell Reports on Tuesday, he and his colleagues used shotgun sequencing to analyze tooth and petrous bone samples from four ancient hunter-gatherer individuals found at a site called Rinnukalns in what is now Latvia. In the process, they identified sequences from a Y. pestis strain dubbed RV 2039 from an ancient man, who appeared to be between 20 and 30 years old when he died an estimated 5,050 to 5,300 years ago.

The team's subsequent analyses — including a phylogenetic analysis that included almost 300 ancient and modern Y. pestis genome sequences — suggested that the Y. pestis strain found in that individual was basal to Y. pestis strains characterized in the past, and part of a lineage that split off from the relatively harmless soil bacteria species Y. pseudotuberculosis some 7,000 years ago.

Still, the authors argued that the available data does not point to a widespread Neolithic plague in the region, in part because the RV 2039 isolate was missing a virulence factor known as YMT that was previously linked to flea-based transmission of the plague bug during the Black Death.

"The genomic and phylogenetic characteristics of RV 2039 are consistent with the hypothesis that this very early Y. pestis form was most likely less transmissible and maybe even less virulent than later strains," the authors wrote, noting that the broader data "do not support the scenario of a prehistoric pneumonic plague pandemic, as suggested previously for the Neolithic decline."

Even so, the infected individual did have Y. pestis in his bloodstream, they explained, suggesting he died of a septicemic infection stemming from a plague-like pathogen that may have been directly acquired from an infected animal through zoonosis.

While it is difficult to know what that animal source may have been after thousands of years, the team suspects that the pathogen may have come from a beaver reservoir, since all rodents seem to make good hosts for Yersinia species and the Castor fiber beaver was a frequently hunted animal in the Rinnukalns region at the time, Krause-Kyora explained. In addition, beavers today are known to carry bugs from the ancestral Y. pseudotuberculosis lineage, and the ancient RV 2039 strain contained some gene variants beyond the missing YMT factor that resemble those in Y. pseudotuberculosis.

"Isolated cases of transmission from animals to people could explain the different social environments where these ancient diseased humans are discovered," Krause-Kyora said in a statement. "We see it in societies that are herders in the steppe, hunter-gatherers who are fishing, and in farmer communities — totally different social settings but always spontaneous occurrence of Y. pestis cases."

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