Probing the zooarchaeological record across time and space for ancient pathogen DNA

Zoonoses are among the greatest threats to human health, with many zoonotic pathogens believed to have emerged following the Neolithic transition. Palaeomicrobiological investigations of the zooarchaeological record hold potential to uncover the reservoirs, host ranges, and host adaptations of zoonotic pathogens in the past, but face challenges in identifying promising specimens and pathogen DNA preservation. We perform palaeopathological and genetic examinations of 346 skeletal elements from domesticated and wild animals collected from 34 Eurasian sites dating across the last six millennia. We identify 116 signatures of 29 ancient (opportunistic) pathogens and find support that palaeopathological lesions provide guidance for specimen selection. For two pathogen species, Erysipelothrix rhusiopathiae and Streptococcus lutetiensis, we confirm their ancient authenticity using phylogenetics, showcasing an approach to explore the relationship between ancient low-coverage genomes and their modern-day relatives. Our work presents a pathway to understanding prehistoric zoonotic diseases by integrating zooarchaeological, palaeopathological, and genetic data.