Sheep helped spread early form of the plague thousands of years ago

By Stephen Beech

Sheep helped spread an early form of the plague, suggests new research.

The bacterium that causes bubonic plague has been identified in a 4,000-year-old sheep, indicating that livestock played a role in spreading the deadly disease.

An increase in livestock herding during the Bronze Age may have led to greater contact between humans, animals, and wild reservoirs of the plague, say scientists.

They explained that, around 5,000 years ago, a mysterious form of plague spread throughout Eurasia, only to disappear 2,000 years later.

Known only from ancient DNA, the ‘LNBA plague’ lineage has left scientists puzzled about its origin and transmission.

Now the ancient plague has been identified in an animal for the first time - a 4,000-year-old domesticated sheep excavated at Arkaim in present-day Russia.

The research team says that different lines of evidence suggest that plague infections in both human and sheep stem from "spillover" of a still unknown wild reservoir, and that widespread sheep herding during the Bronze Age brought pastoralist communities into closer contact with the reservoir.

The new study, published in the journal Cell, reveals the connections between domesticated animals and the spread of one of the world's most infamous bacteria, providing insight into how the pathogen was so successful in infecting people across thousands of miles over hundreds of years.

The research team explained that the majority of human pathogens known today have a zoonotic origin, meaning they jumped from animals into humans - a process known as "spillover".

A growing body of evidence suggests that many of the infectious diseases they cause emerged within the last 10,000 years - overlapping with the domestication of livestock and pets and pointing to man's increasingly close relationships with those animals as the source of those diseases in humans.

Plague is among the most deadly zoonotic diseases known.

Spread by fleas living on rats, it has killed millions of people throughout history, most notably during the 14th-century Black Death in which more than a third of the population of Europe died.

But a genetically distinct, prehistoric form of plague circulated throughout Eurasia, beginning around 5,000 years ago.

Known today as the Late Neolithic Bronze Age (LNBA) lineage, it infected humans for nearly 3,000 years before vanishing, presumably going extinct.

The research team explained that the LNBA lineage lacks the key "genetic toolkit" for flea transmission of both historic and modern plaque strains, making its manner of transmission enigmatic.

Study lead author Ian Light-Maka, a doctoral candidate at the Max Planck Institute for Infection Biology (MPIIB), Germany, said: “One of the first steps in understanding how a disease spreads and evolves is to find out where it's hiding, but we haven’t done that yet in the ancient DNA field.

“We have over 200 Y. pestis genomes from ancient humans, but humans aren’t a natural host of plague.”

An international research team investigated the bones and teeth of Bronze Age livestock at Arkaim.

They identified the 4,000-year-old sheep infected with the same LNBA lineage of Y. pestis that was infecting people at the time.

Study co-author Dr. Taylor Hermes, of the University of Arkansas, said: “Arkaim was part of the Sintashta cultural complex and offered us a great place to look for plague clues.

"They were early pastoralist societies without the kind of grain storage that would attract rats and their fleas - and prior Sintashta individuals have been found with Y. pestis infections.

"Could their livestock be a missing link?”

Comparing the ancient Y. pestis genome from the sheep to other ancient and modern genomes revealed that the sheep Y. pestis genome was a "very close" match to one that had infected a human at a nearby site at around the same time.

Professor Christina Warinner, of Harvard University, said: "If we didn't know it was from a sheep, everyone would have assumed it was just another human infection - it's almost indistinguishable.”

From parts of the world where Y. pestis is still endemic, it is known that sheep can become infected through direct contact with carcasses of infected animals, such as rodents, the natural reservoir of the pathogen, and that can spark local plague outbreaks in humans if the sheep are not properly butchered or cooked.

The researchers believe such a scenario could have also spread LNBA plague in prehistory, linking human and sheep infections.

Warriner said: “The Sintashta-Petrovka culture is famous for their extensive herding over vast pastures aided by innovative horse technologies, and this provided plenty of opportunity for their livestock to come into contact with wild animals infected by Y. pestis.

“From then on it is just one more short hop into humans.”

Study senior author Dr. Felix Key, of the MPIIB, said: “The ancient sheep as well as human infections are likely isolated spillovers from the unknown reservoir, which remains at large.

"Finding that reservoir would be the next step.”

But, despite the new insights, the team says major questions still remain unsolved, such as how the pathogen spread so far and wide over short periods of time.

They believe sheep and humans are unlikely to have been the main agents spreading the disease since there are examples of nearly identical LNBA Y. pestis genomes at the same time but thousands of miles apart, too far for sick humans or terrestrial animals to travel.

The research team believes the search for pathogens in ancient animal remains is just beginnin,g as archaeological digs can yield tens of thousands of bones, and results from previous excavations are waiting to be studied further.

Dr. Key added: “I think there will be more and more interest in analysing these collections - they give us insights that no human sample can.”