Lethal plague outbreaks in Lake Baikal hunter-gatherers 5,500 years ago

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The analysis of ancient pathogen genomes has significantly expanded our understanding of the evolutionary history of human infectious diseases (for example, Salmonella enterica 4 and hepatitis B 5 ), although this has principally been in the context of farming or pastoralist communities. Y. pestis , the aetiological agent of plague, is perhaps the most studied in this regard, and has had devastating consequences on human populations for millennia. Historical outbreaks of plague account for some of the most fatal events in human history 1 . The recovery of ancient DNA from plague victims has afforded extraordinary insights into the origins and evolution of plague at the time of these events 6 , 7 , and, remarkably, revealed infections in prehistoric individuals across Europe 8 . Historically and today, plague is associated with transmission via fleas from rodents, which successfully adapted to a human commensal niche in the Neolithic 9 . Genomic analysis of prehistoric plague indicates that in early diverging strains, key genetic adaptations required for flea-mediated transmission of the disease and bubonic infection are absent 2 , 3 , leading to uncertainty over the transmission route and severity of these strains.

The detection of early plague cases across multiple generations of Late Neolithic farmers has been used to link outbreaks of the disease to a prolonged demographic decline between about 5,300–4,900 calibrated years before the present (cal  bp ) 10 , 11 , although an alternative explanation attributes the decline to agricultural crisis 12 , 13 . The former interpretation has been controversial, with others suggesting infections as more closely resembling benign foodborne enteritis 14 . The similarity or otherwise of these early strains to Y. pseudotuberculosis —the closest relative of Y. pestis —has been an important point of interest through such discussions, and based on existing ancient genomes, Y. pestis has been estimated to have diverged from Y. pseudotuberculosis some time in the past 50,000 years (refs. 8 , 11 , 15 ).

Studies of prehistoric plague genomes from Late Neolithic and Bronze Age (LNBA) strains predominantly date to between 4700–2400 cal  bp (refs. 3 , 8 , 16 ), and are typically defined as one of two lineages, depending on the presence (LNBA+) or absence (LNBA−) of the ymt gene 3 . ymt encodes Yersinia murine toxin, which enhances bacterial survival in the flea digestive tract during the transition period between rodent and human hosts, and thereby the flea bite-transmitted bubonic form of plague in humans 17 . Lineages of Y. pestis that diverged prior to these LNBA clades have also been identified in a handful of Neolithic Swedish individuals (5200-4850 cal  bp ) 10 , 11 and a Latvian individual with western hunter-gatherer ancestry (5300–5050 cal  bp ) 15 . These genomes lack classic virulence genes ( YpfΦ prophage and ymt ), although pangenomic analysis revealed the presence of the locus encoding for Y. pseudotuberculosis -derived mitogen (YPM), a superantigenic toxin associated with Y. pseudotuberculosis (but not later Y. pestis strains). This raises intriguing questions about the possible severity of early strains of plague; subsequent LNBA− strains show substantial gene loss, although the virulence potential of these are unknown 3 . Evidence regarding the demographic impact of plague infection on prehistoric populations has so far been lacking in these studies.

Middle Holocene hunter-gatherers around Lake Baikal, southeast Siberia, have been the focus of intensive archaeological study by the Baikal Archaeology Project, yielding important datasets for framing prehistoric hunter-gatherer lifeways 18 , 19 . These groups demonstrate remarkable continuity of hunter-gatherer lifeways and subsistence, evidenced by an extensive archaeological record of mortuary sites from between about 8500–3500 cal  bp (ref. 20 ). The genomes of sampled hunter-gatherers indicate a long-term continuum of Ancient North Eurasian and North East Asian ancestry until c. 4500–4000 cal bp (refs. 21 , 22 ) (Extended Data Figs. 1 and 2 ). By this period, cases of plague from human remains corresponding to the LNBA− strain are documented sporadically among Early Bronze Age burials 22 , 23 . Zoonotic spillover events causing plague infections in this region remain a major health concern to this day 24 . These are principally associated with marmots, the primary zoonotic reservoir of plague in the region 25 , 26 . To explore health and community structure in prehistoric hunter-gatherer groups, we analysed ancient human and pathogen DNA from four cemetery sites in Cis-Baikal (the lake’s western and northern region) across two separate outbreaks dated to 5520–5265 cal  bp and 5315–4235 cal  bp (95.4% confidence intervals for modelled date ranges based on individuals with detected plague cases, corrected for freshwater reservoir effects; Supplementary Note  4 ). The long tail for the second outbreak date ra…