Plague emerged earlier than thought and hit hunter-gatherers hard

Ancient genomes from Siberian graves reveal that plague was already lethal in small hunter-gatherer communities, reshaping ideas about when and how deadly epidemics first emerged.

Study: Lethal plague outbreaks in Lake Baikal hunter-gatherers 5,500 years ago. Image Credit: nobeastsofierce / Shutterstock

In a recent study published in the journal Nature, a group of researchers investigated the origins, transmission patterns, genetic characteristics, and mortality impact of early Yersinia pestis infections among prehistoric hunter-gatherer communities near Lake Baikal in Siberia.

Background

Could devastating plague outbreaks have occurred long before cities, agriculture, and dense human settlements emerged? Plague is one of the deadliest infectious diseases in human history and is best known for events such as the Black Death.

Previous ancient deoxyribonucleic acid (DNA) studies identified early plague strains in prehistoric Europe, but their ability to cause severe disease remained uncertain because they lacked some of the virulence genes associated with later bubonic plague. Understanding how the early strains of plague spread can help trace the evolution of plague transmission. 

About the study

The researchers examined ancient human remains found at four hunter-gatherer cemeteries near Lake Baikal in southeastern Siberia: Ust’-Ida I, Shumilikha, Bratskii Kamen, and Serovo. They used shotgun sequencing on DNA from 46 late Neolithic individuals spanning two modelled outbreak ranges, 5520-5265 and 5315-4235 calibrated years BP, with the highest-likelihood range for the later phase estimated at approximately 5050-4850 calibrated years BP to generate genetic data, which was then examined for the presence of infectious agents, focusing particularly on identifying Yersinia pestis (the bacterium that causes plague).

a, Locations of affected cemeteries on the Angara River northwest of Lake Baikal, and IBD sharing between the sampled occupants of cemeteries (pairwise sharing lines between sites; greyscale ramp indicates total IBD sharing in segments larger than 3 centimorgans (cM) totaling more than 10 cM in pairwise relationships between sites. Inset represent the sampled individuals at each site (31 Ust’-Ida I, 8 Bratskii Kamen, 2 Serovo and 5 Shumilkha), with plague detections indicated, and shared graves indicated by shaded areas around individuals. Maps created using Natural Earth Data. b, Kernel density estimates plotted within Bayesian models of the date ranges for the early (red) and late (dark yellow) phases of plague outbreaks at Baikal. Lighter shaded areas correspond to the summed probability distributions prior to modeling; dates used are from individuals identified with plague only. Inset, 95.4% confidence intervals for modeled date ranges at Baikal are shown compared with those from other pre-LNBA plague cases: RV2039 from Latvia, Warberg 1 and Warberg 2 from Germany, and FRA102 from Sweden. c, Kernel density estimate modeled radiocarbon date distributions for the four cemetery sites, for all radiocarbon-dated post-weaning age humans (or associated deer tooth pendants), irrespective of DNA sampling. Radiocarbon date modeling undertaken with OxCal v.4.4.4.

a, Locations of affected cemeteries on the Angara River northwest of Lake Baikal, and IBD sharing between the sampled occupants of cemeteries (pairwise sharing lines between sites; greyscale ramp indicates total IBD sharing in segments larger than 3 centimorgans (cM) totaling more than 10 cM in pairwise relationships between sites. Inset represent the sampled individuals at each site (31 Ust’-Ida I, 8 Bratskii Kamen, 2 Serovo and 5 Shumilkha), with plague detections indicated, and shared graves indicated by shaded areas around individuals. Maps created using Natural Earth Data. b, Kernel density estimates plotted within Bayesian models of the date ranges for the early (red) and late (dark yellow) phases of plague outbreaks at Baikal. Lighter shaded areas correspond to the summed probability distributions prior to modeling; dates used are from individuals identified with plague only. Inset, 95.4% confidence intervals for modeled date ranges at Baikal are shown compared with those from other pre-LNBA plague cases: RV2039 from Latvia, Warberg 1 and Warberg 2 from Germany, and FRA102 from Sweden. c, Kernel density estimate modeled radiocarbon date distributions for the four cemetery sites, for all radiocarbon-dated post-weaning age humans (or associated deer tooth pendants), irrespective of DNA sampling. Radiocarbon date modeling undertaken with OxCal v.4.4.4

Radiocarbon dating was performed to establish the chronology of burials and outbreak phases. Human genomic data were also examined to reconstruct biological relationships among individuals and identify family groups affected by infection. Identity-by-descent analysis was also performed on the individuals to evaluate kinship patterns, in addition to examining the demographic structure of the population using mortality profiles by age and sex.

Researchers studied the evolution of pathogens by reconstructing ancient genomic records from individuals infected with plague, then comparing the results to prehistoric and modern Yersinia genomes. They used phylogenetic analyses coupled with Bayesian dating methods and comparisons of genome sequences to identify evolutionary relationships and establish the timing of plague emergence. Other aspects of their investigation included examining classic plague virulence genes, plasmids, and pangenomic variation around the ypm locus, as well as utilizing pangenomic methods to explore the virulence of the ancient strains. The archaeological record, burial practices, and burial patterns were used to construct a picture of plague's epidemiological effect on hunter-gatherer societies.

Study results

The investigation revealed an unexpectedly high detection rate of plague infection among the sampled individuals. Evidence of Yersinia pestis was detected in 18 of 46 individuals, representing a detection rate of approximately 39%. The infected individuals were distributed across four cemeteries and belonged to two distinct outbreak phases separated by roughly four to six centuries. The data suggest that two documented outbreak phases impacted the hunter-gatherer populations around Lake Baikal, rather than isolated events.

According to genomic studies, the strains from Lake Baikal diverged ancestrally from the known clade of ancient and modern Yersinia pestis lineages. These strains diverged before all previously identified ancient and modern plague lineages, helping to constrain the origin of plague to a time before approximately 5,700 years ago and indicating that the bacterium emerged before then.

By examining genetic relationships among humans, researchers determined that many of the infected belonged to closely related families. Several of the graves that contained infected relatives, including siblings, cousins, a nephew and aunt, and groups of young children, were spatially close to one another, and the modeled radiocarbon dates associated with those individuals were similar. This clustering of family infections and clustering by radiocarbon date are consistent with the hypothesis that plague spread rapidly within communities over a short period of time. The data were consistent with possible person-to-person transmission, potentially through pneumonic transmission, rather than proving a specific route.

The mortality patterns provided strong but indirect evidence that these outbreaks were lethal. The two cemeteries with multiple plague detections displayed unusually high childhood mortality compared with other regional hunter-gatherer burial sites. Mortality peaked among children aged approximately 7.5 to 11 years, while deaths among young adults were relatively uncommon. The demographic profiles differed significantly from expected mortality patterns in comparable prehistoric populations.

Genetic examination of the pathogen revealed that the ancient strains lacked the Yersinia murine toxin (ymt) gene and the YpfΦ prophage, both of which are important for classical flea-borne bubonic plague transmission. However, the strains possessed the Yersinia pseudotuberculosis-derived mitogen (ypm) gene, which encodes a potent superantigen capable of triggering excessive immune responses. The detected ypm variant was closest in sequence similarity to the modern ypmA form, regarded as the most virulent known ypm variant, although the ancient sequence differed at three positions. This finding could partly help explain the disproportionately high mortality observed among younger individuals, but the authors note that functional studies are needed to assess the variant’s actual impact.

The researchers also identified ancestral genetic features that disappeared from later plague lineages, suggesting that early plague possessed a unique combination of characteristics during its transition from Yersinia pseudotuberculosis to Yersinia pestis. Together, the archaeological, demographic, and genetic evidence provided strong support for the conclusion that these early plague strains were capable of causing severe disease and death despite lacking the genetic adaptations associated with classical bubonic plague.

Conclusion

The study shows that lethal plague outbreaks affected hunter-gatherer communities around Lake Baikal approximately 5,500 years ago, making them the earliest known plague outbreaks identified to date. This suggests that dense agricultural societies and their larger populations were not necessary precursors to the spread of plague and other infectious illnesses.

The epidemiological, ecological, and genetic evidence also indicates that the populations affected by these two outbreak phases across four cemeteries showed mortality patterns consistent with acute, plague-associated mortality, particularly among children, and probably reflected zoonotic spillover from wild rodent reservoirs, while also showing evidence consistent with human-to-human transmission.

The results provide important insights into the early evolution of Yersinia pestis and highlight the enduring significance of zoonotic diseases in shaping human history. Further study is required to determine whether the earlier strains of plague caused significant death and how they spread within prehistoric human populations.

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Journal reference:
  • Macleod, R., Seersholm, F. V., De Sanctis, B., Lieverse, A., Timpson, A., Schulting, R., Stenderup, J. T., Gaunitz, C., Vinner, L., Goriunova, O. I., Bazaliiskii, V. I., Vasilyev, S. V., Jessup, E., Wang, Y., Bronk Ramsey, C., Thomas, M. G., Corbett-Detig, R., Iversen, A. K. N., Weber, A. W., Sikora, M., & Willerslev, E. (2026). Lethal plague outbreaks in Lake Baikal hunter-gatherers 5,500 years ago. Nature. 654. 697-705. DOI: 10.1038/s41586-026-10540-5, https://www.nature.com/articles/s41586-026-10540-5
Vijay Kumar Malesu

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Vijay Kumar Malesu

Vijay holds a Ph.D. in Biotechnology and possesses a deep passion for microbiology. His academic journey has allowed him to delve deeper into understanding the intricate world of microorganisms. Through his research and studies, he has gained expertise in various aspects of microbiology, which includes microbial genetics, microbial physiology, and microbial ecology. Vijay has six years of scientific research experience at renowned research institutes such as the Indian Council for Agricultural Research and KIIT University. He has worked on diverse projects in microbiology, biopolymers, and drug delivery. His contributions to these areas have provided him with a comprehensive understanding of the subject matter and the ability to tackle complex research challenges.    

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