A prehistoric East-Asian Yersinia pestis genome and a ~5.3 ka trans-Eurasian expansion of plague

Plague, caused by Yersinia pestis, has affected human societies for millennia, yet the timing, scale and biological shifts underlying its earliest spread remain unclear. Here, we screened 1,400 ancient human remains from eastern Eurasia (8,000-400 cal. BP) and recovered three prehistoric Y. pestis genomes, including one from East Asia. Integrating these data with 136 published ancient and modern Y. pestis genomes, we resolved a trans‑Eurasian polytomy dated to ~5.3 ka BP that links Scandinavia, Central Europe, and northern China. Low SNP distances and tip-dating indicate splits over century‑scale intervals across > 7,500 km (median lower-bound dispersal rate of 32.9 km yr⁻¹), consistent with rapid long-distance dispersal. Mapping variation onto the deep phylogeny showed that the basal stem of the LNBA⁺ lineage is the only one of the seven deep phases examined to show significant enrichment of disruptive genomic remodeling relative to the genome-wide background distribution of mutation categories, including acquisition of the ymt gene and multiple gene‑disrupting indels and gene losses. This phylogenetic concentration is consistent with an early episode of adaptation associated with later flea-adapted lineages. Our results extend the prehistoric record of plague into East Asia and refine the timing and scale of its earliest trans-Eurasian expansion. Plague, caused by the pathogen Yersinia pestis, has affected human societies for millennia. Here, the authors screened 1,400 ancient human remains from eastern Eurasia and recovered three prehistoric Y. pestis genomes, extending the prehistoric record of plague into East Asia and refining the timing and scale of its earliest trans-Eurasian expansion.