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Prehistoric Plague Pandemic Probable According to Ancient DNA Analysis

NEW YORK (GenomeWeb) – An international research team led by investigators in Denmark, France, and Sweden has found genetic evidence that the plague pathogen, Yersinia pestis, caused problems for European populations as far back as the Neolithic Period. 

"Our results are consistent with the existence of a prehistoric plague pandemic that likely contributed to the decay of Neolithic populations in Europe," the authors wrote in a study published online today in Cell.

Using ancient and modern-day Y. pestis genotypes, phylogenetics, and molecular clock analyses — in combination with archeological data and sequence data from a 4,900-year-old Swedish gravesite — the researchers saw hints that Y. pestis spread throughout Eurasia in the wake of a Neolithic decline that occurred within the last 5,300 years.

The pathogenic version of Y. pestis found in the Neolithic Swedish farming population belonged to a lineage that is basal to those involved in Bronze Age or modern-day Y. pestis outbreaks, the team reported. In combination with other data at hand, the group speculated that it may have evolved and spread along migration routes from large European "mega-settlements" that were home to as many as 10,000 to 20,000 people before they were destroyed or collapsed.

"If plague evolved in the mega-settlements, then when people started dying from it, the settlements would have been abandoned and destroyed. This is exactly what was observed in these settlements after 5,500 years ago," senior author Simon Rasmussen said in a statement. "Plague would also have started migrating along all the trade routes made possible by wheeled transport, which had rapidly expanded throughout Europe in this period."

Rasmussen was based at the Technical University of Denmark when the study was done and is currently affiliated with the University of Copenhagen Novo Nordisk Foundation Center for Protein Research.

His team's analyses relied, in part, on a genome sequencing analysis of a 4,867- to 5,040-year-old Y. pestis isolate obtained from a 20-year-old woman whose remains were found at an ancient gravesite in western Sweden that was excavated nearly a decade ago.

Based on reads spanning more than 79 percent of the pathogen's genome to an average depth of 2.7-fold, along with between 1.7- and more than 14-fold coverage of three Y. pestis plasmids, they realized that they were dealing with a Y. pestis strain that had not been encountered in prior studies.

Although the ancient Swedish isolate contained genes implicated in pneumonic plague disease, a phylogenetic analysis based on 183 ancient and modern-day Y. pestis sequences and 27 Y. pseudotuberculosis genomes suggested that it falls at or near the base of the Y. pestis family tree, diverging from other strains an estimated 5,700 years ago based on a molecular clock analysis.

In contrast, the team noted that a lineage leading to the strains causing disease in the Bronze Age and more recently split off some 5,100 to 5,300 years ago. Even so, a genomic analysis of almost 1,100 ancient Europeans argued against a significant role for human migrations in the spread of Neolithic plague, since it turned up in genetically distinct populations showing little admixture.

Rather, the researchers suspect that the Neolithic form of the plague pathogen may have moved along trade routes originating at large settlements where tens of thousands of people lived in close quarters with animals and stored food at sites with poor sanitation.

Together, the authors suggested, the analyses "revealed that multiple and independent lineages of Y. pestis branched and expanded across Eurasia during the Neolithic decline, spreading most likely through early trade networks rather than massive human migrations." 

In a related study published in the Proceedings of the National Academy of Sciences last week, a University of Oslo-led team profiled five medieval Y. pestis isolates from France, Norway, and the Netherlands to explore the roots of the Second Plague Pandemic.

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