Analysis of 3800-year-old Yersinia pestis genomes suggests Bronze Age origin for bubonic plague

Maria A Spyrou,Aditya K Lankapalli,Johannes Krause,Alexander Herbig,Aida Andrades Valtueña,Victor A Tsybin,Aleksandr Khokhlov,Vitaly V Kondrashin,Kirsten I Bos,Denise Kühnert,Rezeda I Tukhbatova,Chuan-Chao Wang

doi:10.1038/s41467-018-04550-9

Abstract

The origin of Yersinia pestis and the early stages of its evolution are fundamental subjects of investigation given its high virulence and mortality that resulted from past pandemics. Although the earliest evidence of Y. pestis infections in humans has been identified in Late Neolithic/Bronze Age Eurasia (LNBA 5000–3500y BP), these strains lack key genetic components required for flea adaptation, thus making their mode of transmission and disease presentation in humans unclear. Here, we reconstruct ancient Y. pestis genomes from individuals associated with the Late Bronze Age period (~3800 BP) in the Samara region of modern-day Russia. We show clear distinctions between our new strains and the LNBA lineage, and suggest that the full ability for flea-mediated transmission causing bubonic plague evolved more than 1000 years earlier than previously suggested. Finally, we propose that several Y. pestis lineages were established during the Bronze Age, some of which persist to the present day.

Highlights

The origin of Yersinia pestis and the early stages of its evolution are fundamental subjects of investigation given its high virulence and mortality that resulted from past pandemics
We screened a total of 64 million shotgun next-generation sequencing (NGS) reads (Supplementary Table 1) from nine teeth of nine individuals recovered from kurgan burials in the Samara region to assess the endogenous human DNA content and the possible presence of Y. pestis
As Megan ALignment Tool (MALT) has previously proven to be an efficient tool in binning reads from complex metagenomic datasets into their respective bacterial taxa and has been successfully used for identifying pathogen DNA in archaeological material[27], we considered individuals as putatively positive only when reads were assigned to Y. pestis by both conventional read-mapping and MALT

Summary

Introduction

The origin of Yersinia pestis and the early stages of its evolution are fundamental subjects of investigation given its high virulence and mortality that resulted from past pandemics. Plague has a near-worldwide distribution and is maintained within sylvatic rodent populations[9] Several of these rodent reservoirs were established during the third plague pandemic that began in 19th century China[10,11], many of those identified in Central and East Asia and most notably those of the Caspian Sea region harbour Y. pestis strains that occupy basal positions in the global phylogeny (i.e., 0.PE2)[12]. Recent ancient genomic investigations of Y. pestis have identified its earliest known variants in Eurasia during the Late Neolithic/Bronze Age period (LNBA) that show genetic characteristics incompatible with arthropod adaptation These strains, have been considered incapable of an efficient flea-based transmission[2]; the alternative early-phase transmission could have provided an independent means of arthropod dissemination[2,3,21]. The mechanism by which the LNBA lineage caused human disease is unclear, its frequency in Eurasia during the Bronze Age[2,3] and its phylogeographic pattern that mimics contemporaneous human migrations are noteworthy[3]

Methods

Results

Conclusion