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

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.

Ancient pathogen genomics as an emerging tool for infectious disease research

“…Pathogen aDNA is thought to be preserved within the remnants of the pulp chamber, likely as part of desiccated blood 8,17 . Consequently, tooth sampling has proved successful in the retrieval of whole genomes or genome wide data (that is, low coverage genomes that have provided limited analytical resolution) from ancient bacteria such as Y. pestis 20,[30][31][32][33][34][35][36][37][38][39] , Borrelia recurrentis 40 and Salmonella enterica 41 ; ancient eukaryotic pathogens such as Plasmodium falciparum 42 ; and ancient viruses such as hepatitis B virus (HBV) 43,44 and human parvovirus B19 (B19V) 45 . Even M. leprae, which commonly manifests in the chronic form, has been retrieved from ancient teeth 27,28 .…”

“…This technique has contributed to the increased number of specimens from which human genome wide single nucleotide polymorphism (SNP) data could be retrieved 84,85 , even from climate zones that pose challenges to aDNA preservation (pre sented elsewhere [86][87][88] ). In addition, in solutionbased capture has recently become the preferred method for microbial pathogen genome recovery for both bacteria and DNA viruses (for examples, see reFs 34,37,41,43,45,49,50 ). Nevertheless, deep shotgun sequencing alone has also been used for human [89][90][91] and pathogen 28,33,48 high quality…”

“…Subsequently , the genomes are assessed for their coverage depth and gene content for evaluation of their quality , which is also relevant for the comparative identification of virulence genes over their evolutionary time frames. Here, we show an example of virulence factor presence-or-absence analysis in the form of a heat map, as done previously 33,34,37,41 . In addition, a comparison of the ancient genome or genomes with modern genomes can be carried out for single-nucleotide polymorphism (SNP) identification and for assessment of SNP effects (using SnpEff 186 ), which is particularly relevant for variants that seem to be unique to the ancient genome or genomes.…”

“…Its global distribution includes numerous rodent species 144,145 and encompasses regions in eastern Europe, Asia, Africa and the Americas (Fig. 4), where the bacterium persists in active foci, some of which have existed for centuries or even millennia 31,33,34,37,130 . Y. pestis transmission among hosts is facilitated by a flea vector (Fig.…”

AncientYersinia pestisgenomes provide no evidence for the origins or spread of the Justinianic Plague

“…Although the Justinianic Plague was previously thought to represent the first major onslaught of plague in humans (i.e., the First Pandemic), plentiful examples of human infections of Y. pestis are surfacing as far back as the Neolithic (Andrades Valtueña et al, 2017; Rascovan et al, 2019; Spyrou et al, 2018). Here, we present a reanalysis of both DA101 and DA147 genomes which does not seem to support the arguments made by Damgaard et al, 2018.…”