Oldest strains of plague caused deadly outbreaks 5,500 years ago

Plague is commonly associated with rats, crowded medieval cities, and the epidemics that swept across Europe during and after the Middle Ages. 

But a new study published today in the journal Nature shows that the disease was already lethal 5,500 years ago, when it killed humans in small, mobile hunter-gatherer communities -  long before the rise of agriculture and cities created the conditions usually associated with plague epidemics.

An international group of researchers analysed ancient DNA from human remains found at four hunter-gatherer cemeteries in the Lake Baikal region of East Siberia. Using advanced DNA sequencing techniques, the researchers reconstructed ancient bacterial genomes preserved in teeth, revealing previously unknown early strains of plague. 

“Based on the plague DNA, the genetic relationships between the victims, the archaeological analysis and the radiocarbon dating, we’ve built a really clear, complete picture of what happened during these outbreaks,” said Dr Ruairidh Macleod, who conducted the research at the University of Cambridge and the University of Oxford, and is first author of the study.

The study combines genetic, archaeological and radiocarbon evidence to reconstruct how the outbreaks unfolded within the prehistoric groups.

“Whether the earliest forms of plague were mild or virulent has been a matter of debate, but our findings demonstrate that these ancient strains were already highly lethal,” said Professor Eske Willerslev, at the University of Cambridge's Department of Genetics and the University of Copenhagen, who led the research.

In total, DNA from Yersinia pestis - the bacterium that causes plague - was detected in 40 percent of individuals (18 of 46). This is higher than the detection rate reported from some medieval plague pits.

A more lethal disease than previously thought

Previous studies showed that early strains of Yersinia pestis lacked some of the genetic traits that later enabled bubonic plague to spread efficiently via fleas and rodent hosts. This led many researchers to believe that the earliest forms of plague were unlikely to have caused major outbreaks. However, the new study challenges that assumption. 

The mortality profiles at the two largest cemeteries show an exceptionally high number of children and young teenagers among the dead – something that has puzzled archaeologists working on the graves for decades. 

“The unusually high number of children and the short time-span was a real puzzle that we’ve been trying to solve since the 1990s. Finding out that plague was the cause is extraordinary, but it makes so much sense,” said archaeologist Andrzej Weber of the University of Alberta, Principal Investigator of the Baikal Archaeology Project.

Radiocarbon dating showed that many of the burials occurred within a very short time span. In several cases, siblings or parents and children appear to have died and been buried together.

Did extreme immune responses cause death? 

The ancient plague strains also carried a unique superantigen – a toxin-producing genetic factor not seen in historic plague strains. Superantigens can trigger extreme immune responses and are associated with severe inflammatory complications, likely increasing the severity of infection.

“This finding changes our understanding of the earliest plague outbreaks: even before the bacterium evolved efficient flea-borne transmission, these ancient strains appear to have carried a potent combination of virulence factors that could make infection highly lethal,” said senior author Martin Sikora, Associate Professor at the University of Copenhagen.

Together, the findings suggest that the earliest known plague outbreaks may already have been as deadly as later historical forms of the disease, especially for children, even without flea-borne transmission.

The study also supports the idea that plague may have originated in Central or North-East Asia before later spreading across Eurasia through wild rodent reservoirs. Archaeological evidence suggests these hunter-gatherers interacted closely with marmots – large burrowing rodents that still carry plague today – and researchers believe the outbreaks may have spread directly from infected marmots into humans.

Reference: Macleod, R. et al: ‘Lethal Plague Outbreaks in Lake Baikal Hunter-Gatherers 5500 Years Ago.’ Nature, June 2026. DOI: 10.1038/s41586-026-10540-5

Adapted from a press release by the Globe Institute, University of Copenhagen.