Lethal Plague Outbreaks in Lake Baikal Hunter-gatherers 5500 Years Ago

Abstract

The rise of zoonotic diseases in prehistory is often associated with the Neolithic agricultural transition1,2. In particular, plague has been linked to population declines in Late Neolithic Europe3,4. Although plague is amongst the most devastating diseases in human history, early strains of Yersinia pestis, the causal agent of plague, lack virulence factors required for the bubonic form5, and their severity remains unclear. Here, we describe the oldest strains of plague reported so far, associated with two early phases of outbreaks among prehistoric hunter-gatherers in the Lake Baikal region in East Siberia, beginning from [~]5600-5400 years ago (cal. BP). These outbreaks occur across four hunter-gatherer cemeteries; the largest of these (Ust-Ida I) has a 38.7% detection rate for plague infection (39% detection across all sites). By reconstructing kinship pedigrees, we show that small familial groups are affected, consistent with human-to-human spread of the disease, and the first outbreak occurred within a single generation. Intriguingly, the infections appear to have resulted in acute mortality events, especially among children. Zoonotic transmission is separately indicated by a Brucella infection in one of the children. Interestingly, we see differences in functional genomic variants in the prehistoric plague strains, including in the ypm superantigen known from Y. pseudotuberculosis today. The new strains diverge ancestrally to all known Y. pestis diversity and push back the Y. pestis divergence from Y. pseudotuberculosis by some 2000 years6. Our results show that plague outbreaks happen earlier than previously thought and that these early outbreaks were indeed lethal. The findings challenge the common notion that high population densities and lifestyle changes during the Neolithic transition were prerequisites for plague epidemics.