Summary Infectious diseases have had devastating impacts on human populations throughout history. Still, the origins and past dynamics of human pathogens remain poorly understood 1 . To create the first spatiotemporal map of diverse ancient human microorganisms and parasites, we screened shotgun sequencing data from 1,313 ancient human remains covering 35,000 years of Eurasian history for ancient DNA deriving from bacteria, viruses, and parasites. We demonstrate the widespread presence of ancient microbial DNA in human remains, identifying over 2,400 individual species hits in 896 samples. We report a wide range of pathogens detected for the first time in ancient human remains, including the food-borne pathogens Yersinia enterocolitica and Shigella spp., the animal-borne Leptospira interrogans , and the malaria-causing parasite Plasmodium vivax . Our findings extend the spatiotemporal range of previously described ancient pathogens such as Yersinia pestis , the causative agent of plague, Hepatitis B virus , and Borrelia recurrentis , the cause of louse-borne relapsing fever (LBRF). For LRBF we increase the known distribution from a single medieval genome to 31 cases across Eurasia covering 5,000 years. Grouping the ancient microbial species according to their type of transmission (zoonotic, anthroponotic, sapronotic, opportunistic, and other), we find that most categories are identified throughout the entire sample period, while zoonotic pathogens, which are transmitted from living animals to humans or which have made a host jump into humans from animals in the timeframe of this study, are only detected from ∼6,500 years ago. The incidence of zoonotic pathogens increased in our samples some 1,000 years later before reaching the highest detection rates ∼5,000 years ago, and was associated with a human genetic ancestry component characteristic of pastoralist populations from the Eurasian Steppe. Our results provide the first direct evidence for an epidemiological transition to an increased burden of zoonotic infectious diseases following the domestication of animals 2 . However, they also reveal that the spread of these pathogens first becomes frequent thousands of years after increased animal-human contact, likely coinciding with the pastoralist migrations from the Eurasian Steppe 3,4 . This study provides the first spatiotemporal map of past human pathogens using genomic paleoepidemiology, and the first direct evidence for an epidemiological transition of increased zoonotic infectious disease burden after the onset of agriculture, through historical times.

The landscape of ancient human pathogens in Eurasia from the Stone Age to historical times