The Stone Age Plague and Its Persistence in Eurasia

Abstract

Yersinia pestis, the etiologic agent of plague, is a bacterium associated with wild rodents and their fleas. Historically it was responsible for three pandemics: the Plague of Justinian in the 6 century AD, which persisted until the 8 century [1]; the renowned Black Death of the 14 century [2, 3], with recurrent outbreaks until the 18 century [4]; and the most recent 19 century pandemic, in which Y. pestis spread worldwide [5] and became endemic in several regions [6]. The discovery of molecular signatures of Y. pestis in prehistoric Eurasian individuals and two genomes from Southern Siberia suggest that Y. pestis caused some form of disease in humans prior to the first historically documented pandemic [7]. Here, we present six new European Y. pestis genomes spanning the Late Neolithic to the Bronze Age (LNBA; 4,800 to 3,700 calibrated years before present). This time period is characterized by major transformative cultural and social changes that led to cross-European networks of contact and exchange [8, 9]. We show that all known LNBA strains form a single putatively extinct clade in the Y. pestis phylogeny. Interpreting our data within the context of recent ancient human genomic evidence that suggests an increase in human mobility during the LNBA, we propose a possible scenario for the early spread of Y. pestis: the pathogen may have entered Europe from Central Eurasia following an expansion of people from the steppe, persisted within Europe until the mid-Bronze Age, and moved back toward Central Eurasia in parallel with human populations.

AncientYersinia pestisgenomes from across Western Europe reveal early diversification during the First Pandemic (541–750)

“…Although recent palaeogenetic analyses have been able to reconstruct an ancient form of Y. pestis that infected humans as early as in prehistoric times (2,800 to 1,700 BCE (3–5)) the First Pandemic (541–750) is the earliest historically recorded pandemic that has been clearly attributed to Y. pestis (6, 7), starting with the fulminant Justinianic Plague (541–544). It was later followed by the Second Pandemic, which started with the Black Death of 1347–1353 (8, 9) and persisted in Europe until the 18 th century (10–12).…”

A seventeenth-centuryMycobacterium tuberculosisgenome supports a Neolithic emergence of theMycobacterium tuberculosiscomplex

“…Innovations and improvements in ancient DNA retrieval and enrichment methods, however, have brought this expectation firmly into the realm of the possible (30,69). Ancient bacterial pathogen genomes have now been retrieved from remains from up to 5,000 years before present (70–72) and recent studies have reported the recovery of human genomes from up to 15,000 year-old remains from north Africa (73,74).…”

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

“…For the phylogenetic analyses, we used 166 previously published modern Y. pestis genomes (Cui et al, 2013; Eroshenko et al, 2017; Kislichkina et al, 2015; Zhgenti et al, 2015), a Y. pseudotuberculosis reference genome (IP32953; Chain et al, 2004) as an outgroup and the following ancient genomes: nine genomes from Neolithic/Bronze Age contexts (Andrades Valtueña et al, 2017; Rasmussen et al, 2015; Spyrou et al, 2018), one genome of the Justinianic Plague (Altenerding; Feldman et al, 2016), one genome representing Black Death (8291-11972-8124; (Bos et al, 2011), and six genomes of the subsequent second plague pandemic (Observance OBS116, OBS137, OBS110, OBS107, OBS124; Bos et al, 2016); Bolgar, (Spyrou et al, 2016)). A complete list of all Y. pestis genomes used is given in Table S1.…”

“…The recent sequencing of dozens of pathogen genomes reconstructed from ancient DNA enabled increased-resolution phylogeographic studies on the spread of infectious diseases in prehistoric and historic times, especially in the context of human migration, mobility and trade (Andrades Valtueña et al, 2017; Bos et al, 2016; Keller et al, 2019; Namouchi et al, 2018; Rascovan et al, 2019; Rasmussen et al, 2015; Spyrou et al, 2019, 2016; Vågene et al, 2018). This is especially true for plague with its long and richly documented history and the abundance of published ancient genomes of its causative agent, Yersinia pestis .…”

“…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.…”