Unravelling the ecology and virulence of prehistoric plague

The rise of zoonotic diseases in prehistory is often associated with the Neolithic agricultural transition; with plague specifically linked to population declines in Late Neolithic Europe. Although plague is amongst the most devastating diseases in human history, early strains of Yersinia pestis (prior to ~3800 years ago), the causal agent of plague, lack virulence factors required for the bubonic form, and their severity remains unclear. I identified strains of plague associated with early outbreaks among prehistoric hunter–gatherers in the Lake Baikal region in East Siberia, beginning from ∼5500 years ago (cal. BP), with a 39% detection rate for plague across all sites (unexpectedly high, given the very high false negative rate of detection using ancient DNA). Based on kinship pedigrees of the human victims, small familial groups are shown to be 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. Using pangenomic approaches, differences in functional genomic variants in the prehistoric plague strains are observed, including, intriguingly, in the ypm superantigen known from Y. pseudotuberculosis today. These results show that plague outbreaks happen earlier than previously thought and were indeed lethal, challenging the common notion that high population densities and lifestyle changes during the Neolithic transition were prerequisites for plague epidemics. Marmots are the primary zoonotic reservoir for plague in this region, and the ecological context for these outbreaks is considered with regard to a seperate ancient environmental DNA archive of ecosystem evolution I worked on during my PhD for Lake Baikal as well.

Bio Sketch:
Ruairidh Macleod undertook an undergraduate in Biological Anthropology and then a PhD at Cambridge, the latter supervised by professors Eske Willerslev and Matthew Collins. This research focused primarily on north Eurasian hunter-gatherers, particularly from Lake Baikal, but also a large ongoing study of Zvejnieki, Latvia. His interests gradually shifted from conventional popgen to metagenomics, and has also worked on generating environmental DNA records of ecosystem change, with the aim of linking these to changes in human demography and society. Following less than a year as a postdoc in Department of Genetics, Evolution and Environment at University College London, since October 2025, Ruairidh has been a Post-Doctoral Research Fellow at All Souls College, Oxford, where his research focuses on how humans have disrupted ecosystems through time in the past, with a particular focus on human disruption and zoonotic disease outbreaks, using the analysis of ancient DNA. www.asc.ox.ac.uk/person/dr-ruairidh-macleod