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Bronze Age Plague Pathogen Sequences Suggest Early Flea Transmissibility

NEW YORK (GenomeWeb) – By sequencing two Late Bronze Age Yersinia pestis isolates, a team from Germany, Russia, China, and Switzerland has gleaned additional insights into the history of the notorious pathogen behind the bubonic plague.

"Our Y. pestis isolates from around 4,000 years ago possessed all the genetic characteristics required for efficient flea transmission of plague to rodents, humans, and other mammals," first author Maria Spyrou, an archaeogenetics researcher affiliated with Max Planck Institute and the University of Tübingen, said in a statement.

Starting with tooth samples from nine ancient individuals buried in a Russian tomb in the Smara region, Spyrou and colleagues identified two Y. pestis-infected individuals, who appeared to belong to the Srubnaya culture based on their own genetic profiles. They then sequenced plague-causing pathogens isolated from those individuals, dated at around 3,800 years old.

A phylogenetic analysis of the strains, set alongside 177 available modern and ancient Y. pestis sequences, suggested that they belonged to a previously undocumented lineage that emerged roughly 4,000 years ago, but already contained the virulence factors that set bubonic plague apart from more innocuous bacteria. The team reported its work online today in Nature Communications.

Those results suggest that "plague, with the transmission potential that we know today, has been around for much longer than we thought," co-author Kirsten Bos, a palaeopathology researcher at the Max Planck Institute for the Science of Human History, said in a statement.

Prior analyses of ancient Y. pestis have already offered clues to the microbe's spread, as well as the adaptations that pushed it toward its plague-causing abilities. In a paper published in Current Biology last November, for example, Spyrou, Bos, and other members of the Max Planck-led team looked at half a dozen Late Neolithic or Bronze Age isolates, using them to explore plague introduction to Europe.

Even so, an analysis of Bronze Age isolates sequenced by the University of Copenhagen's Eske Willerslev and colleagues in 2015 indicated that those early Eurasian isolates had many known virulence factors but did not contain genetic features compatible with routine transmission to humans via fleas.

For the new study, researchers used in-solution capture and deep Illumina shotgun sequencing to generate Y. pestis and human host sequences for a Bronze Age man known as RT5, producing more than 32-fold average coverage of that Y. pestis genome. An isolate from another infected individual, RT6, was sequenced to an average depth of 1.9-fold.

Their phylogenetic analysis indicated that the isolates in RT5 and RT6 were part of a shared lineage stemming from an ancestor that also led to the pathogens contributing to Black Death, the Justinian Plague, and 19th century plague epidemics in China.

The study also raises new questions about the prevalence and historical spread of Y. pestis lineages, senior author Johannes Krause, director of archaeogenetics at the Max Planck Institute for the Science of Human History and archaeological sciences researcher at the University of Tübingen, said in a statement. He noted that further details may be revealed in the future, as still more ancient plague pathogens get the sequencing treatment.

"Additional Bronze Age and Iron Age plague genomes could help pinpoint key events that contributed to the high virulence and spread of one of humankind's most notorious pathogens," Krause said.

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