Plague swept through groups of hunter-gatherers in southeastern Siberia 5,500 years ago, leaving dozens dead in its wake—with DNA from Yersinia pestis bacteria still trapped inside their teeth.
University of Oxford ancient DNA researcher Ruairidh Macleod and his colleagues recently sequenced the telltale bacterial DNA in teeth from plague victims at four ancient cemeteries in the area around Russia’s Lake Baikal. The tragedy that befell these communities is now the earliest known plague outbreak, courtesy of the oldest strain of Y. pestis ever sequenced.
Unearthing a new backstory for the plague
Until recently, scientists who study the evolution of diseases have held two fairly solid ideas about the origins of plague, the disease caused by Yersinia pestis bacteria. It's a scourge so awful that it has gone down in history as not just a plague but the plague. The first idea is that the earliest strains didn't have the right genetic traits to be really lethal. And the second is that the plague first began menacing humans when the first farmers settled in densely packed towns alongside rats and domestic animals.
But the dead of Ust'-Ida I cemetery, near Lake Baikal, tell a very different story.
"Our findings demonstrate that the earliest known outbreaks of plague occurred in prehistoric hunter-gatherers centuries before infections are observed in Neolithic farmers," wrote Macleod and his colleagues in their recent paper.
That challenges our previous assumption that plague spillover was a side effect of people taking up farming and settling in permanent villages and towns, living closer to each other and to an assortment of animals (and their fleas).
"Much of the accepted theory around epidemiology of disease in the past is that this kind of thing shouldn't occur in hunter-gatherers because hunter-gatherers are constantly moving around the landscape because they're in such small groups all the time," said Macleod in a press conference. "The theory, at least, is that infectious disease can't really take hold and devastate entire communities in this way.”
So much for that theory.
Welcome to the world’s first plague cemetery
The Angara River flows from the depths of Lake Baikal. The people who lived along it thousands of years ago survived by hunting, foraging, and fishing. They would have lived in relatively small groups, but they seem to have stayed connected across hundreds of kilometers through marriage and family ties. Although their lifestyle would have been one of constant movement, they buried their dead in cemeteries such as Ust'-Ida, interring them with offerings of clay pots, stone tools, and bone and antler points.

This map shows the location of Ust'-Ida I and Shumilikha cemeteries near Lake Baikal and the Angara River
Credit:
By Tara Young, taray@ualberta.ca and NASA https://wist.echo.nasa.gov/api/ - NASA's freely offered GDEM https://wist.echo.nasa.gov/api/, Public Domain, https://commons.wikimedia.org/w/index.php?curid=21156871
At Ust'-Ida, archaeologists with the Baikal Archaeology Project unearthed a grim mystery: an unusually high number of dead children, a cluster of radiocarbon dates suggesting that many of the cemetery's occupants died at around the same time, and no evidence of violence. Something tragic happened to this ancient hunter-gatherer community, but what? Archaeologists thought ancient DNA might shed some light on the mystery.
Macleod and his colleagues started with shotgun sequencing, a technique used to identify the DNA sequences in a sample when scientists don't know exactly which organisms they're looking for. They used samples from the roots of 46 ancient people's teeth from four different cemeteries along the Angara River.
And to their complete surprise, they found plague.
Fun fact: Because dental roots are fed by lots of blood vessels, anything in your bloodstream is likely to pass through your teeth at some point, which means if you die with the plague, it may leave its DNA behind in your teeth. “This is really cool evidence that the plague was in the bloodstream, which is lethal,” said co-author Frederik Seersholm, a University of Copenhagen ancient DNA researcher who clearly knows a fun fact when he sees one, in a press conference.
About 11 of the 31 people Macleod and his colleagues tested at Ust'-Ida had Y. pestis DNA in their teeth, and Macleod says that's "consistent with pretty much everybody [in the cemetery] having died of plague," not just those 11. That's because the detection rate for plague DNA in the remains at Ust'-Ida matches that at Smithfield's, a known mass grave specifically for plague victims in London. It's safe to assume everyone buried there had the plague.
"We really didn't know what to expect going into this, so it was a complete surprise that we discovered this really, really early evidence for large-scale lethal outbreaks of plague amongst these hunter-gatherer communities at this point in time," said Macleod in the press conference.
Ancient DNA and future outbreaks
Macleod and his colleagues managed to sequence a full Yersinia pestis genome from at least one of the samples, and it turns out to be the oldest strain of Y. pestis ever sequenced. According to the research, it's very close to the base of the plague family tree, emerging just a few hundred years after Y. pestis last shared a common ancestor with another bacterium called Yersinia pseudotuberculosis. This ancient plague isn't quite the one we're familiar with today or the version that devastated medieval Europe.
This very early version of Yersinia pestis doesn't have some of the genes that made its descendants so virulent; it's missing, for example, a gene that produces Yersinia murine toxin, which helps the bacteria survive passing through a flea's digestive tract on its way from a wild prairie dog to an unlucky hiker. It also lacks the right genes to form buboes (the painful swelling and darkening of the lymph nodes that gives bubonic plague its name). But its genome, not to mention the bodies it left in its wake, reveals that this early strain of Y. pestis was still horrifically deadly and probably deeply unpleasant to have.
"There are really a kind of perfect cocktail of other types of virulence genes that cause it to be so deadly—particularly, unfortunately, for children," said University of Copenhagen evolutionary geneticist Eske Willerslev during the press conference.
Understanding that perfect cocktail could be useful for battling modern epidemics, despite this strain of Y. pestis being so different from the ones circulating now in North America and Asia.
“What it gives you is an idea of which mutations in combination {...} are something that survives in nature,” said Willerslev. Because any combinations of features that work well tend to reappear (in the same microbe or in a different species), he said, studying ancient bacterial DNA “actually gives you some information on how these pathogens, including the plague, will develop.”
Why did the plague kill so many children?
Bubonic plague spreads through flea bites, but pneumonic plague is a respiratory disease, which spreads in a similar way to the flu or COVID-19, and that seems to be how this early version would have passed from person to person. So we can assume it would have come with respiratory symptoms like cough and difficulty breathing, along with fever. But for children, it probably would have been even worse.
When archaeologists plotted the ages of the dead on a graph, they noticed a sharp peak in children between 7 and 11 years old. Adults older than 20, on the other hand, had the lowest death rate. That lines up with data from plague outbreaks thousands of years later in London, when parish records document local children bearing the brunt of the plague's death toll.
The Y. pestis genomes that Macleod and his colleagues sequenced offer a clue about why. According to Iversen, the 5,500-year-old strain carries a gene that makes what’s called a superantigenic toxin: a chemical that triggers a dramatic, disorganized overreaction by the immune system. Children are especially vulnerable to this kind of reaction, said Oxford University immunologist Astrid Iversen during the press conference, because their immune systems are still learning how to respond to pathogens.
Telling the story of an ancient outbreak
The outbreak probably started when the bacteria made the leap from an infected marmot (a type of ground squirrel that's still a common plague carrier in the area) to a single person and then spread like wildfire through several interconnected hunter-gatherer groups along the river. For millennia, people around Lake Baikal have hunted marmots for food and for their fur, and close contact with a plague-ridden marmot can spread the infection. This is how it goes: accidentally inhale a few droplets of blood while skinning your latest kill or eat an undercooked marmot stew, and you’ve just doomed your whole band. And the neighbors.

Why are all the plague reservoirs also things I want to pick up and hug?
Credit:
By Stéphane Magnenat - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=7566004
That scenario is supported by the fact that people at Ust'-Ida carried the same strain of plague as those buried 37 kilometers away at another cemetery, Shumilikha, which is what epidemiologists would expect to see if they were part of the same outbreak. The burial customs at the two cemeteries suggest they belonged to different subcultures within the wider Isakovo tradition, but DNA from the plague victims reveals threads of kinship connecting them—and the plague may have made those threads deadly.
Macleod and his colleagues sequenced the DNA of the plague victims, piecing together how they were related and (through radiocarbon dating) when each member of the family died. That data revealed that the plague seemed to have spread among family members, often killing several at close enough to the same time that siblings often share graves.
"The incidence of detected infections among co-buried kin... would be consistent with the transmission of plague among humans, particularly via pneumonic transmission in the scenario of concurrent deaths," wrote Macleod and his colleagues.
Or as Macleod put it during the press conference, direct spread between people makes a lot more sense than "an outlandish scenario that absolutely everybody got together at the same time and ate the same infected marmot."
At Ust'-Ida, a young boy shares a grave with his aunt; both had Yersinia pestis in their bloodstreams when they died. The aunt also has a teenage niece buried nearby in a grave alongside a teenage boy who isn't biologically related to her (it's hard to tell if they were adopted siblings or cousins, a couple, or just close friends). And the boy's father is buried nearby in yet another grave.
“It's so obvious from the way people are buried… that somebody was around to bury the dead that knew who these people were when they were alive,” said Macleod. “And that adds a really really human element to the scientific work that we've done, seeing the impact on communities and how these communities responded to this very tragic set of events.”
Nature, 2026 DOI: 10.1038/s41586-026-10540-5 (About DOIs).
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