Ancient Yersinia pestis genomes from across Western Europe reveal early diversification during the First Pandemic (541–750)

Abstract

60 The first historically documented pandemic caused by Yersinia pestis started as the Justinianic 61 Plague in 541 within the Roman Empire and continued as the so-called First Pandemic until 62 750. Although palaeogenomic studies have previously identified the causative agent as Y. 63 pestis, little is known about the bacterium’s spread, diversity and genetic history over the course 64 of the pandemic. 65 To elucidate the microevolution of the bacterium during this time period, we screened human 66 remains from 20 sites in Austria, Britain, Germany, France and Spain for Y. pestis DNA and 67 reconstructed six new genomes. We present a novel methodological approach assessing SNPs 68 in ancient bacterial genomes, facilitating qualitative analyses of low coverage genomes from a 69 metagenomic background. Phylogenetic analysis reveals the existence of previously 70 undocumented Y. pestis diversity during the 6th–7th centuries, and provides evidence for the 71 presence of multiple distinct Y. pestis strains in Europe. We offer genetic evidence for the 72 presence of the Justinianic Plague in the British Isles, previously only hypothesized from 73 ambiguous documentary accounts, as well as southern France and Spain, and that southern 74 Germany seems to have been affected by at least two distinct Y. pestis strains. Four of the 75 reported strains form a polytomy similar to others seen across the Y. pestis phylogeny, 76 associated with the Second and Third Pandemics. We identified a deletion of a 45 kb genomic 77 region in the most recent First Pandemic strain affecting two virulence factors, intriguingly 78 overlapping with a deletion found in 17th–18th-century genomes of the Second Pandemic. 79 80 Significance Statement 81 The first historically reported pandemic attributed to Yersinia pestis started with the Justinianic 82 Plague (541–544) and continued for around 200 years as the so-called First Pandemic. To date, 83 only one Y. pestis strain from this pandemic has been reconstructed using ancient DNA. In this 84 study, we present six new genomes from Britain, France, Germany and Spain, demonstrating 85 the geographic range of plague during the First pandemic and showing microdiversity in the 86 Early Medieval Period. Moreover, we detect similar genome decay during the First and Second 87 Pandemic (17th to 18th century) that includes the same two virulence factors, thus providing an 88 example of potential convergent evolution of Y. pestis during large scale epidemics. 89 90 Keywords 91 Justinianic Plague, Ancient DNA, Bacterial evolution, Anglo-Saxons, Merovingians, 92 Visigoths, multiple burials 3 bioRxiv preprint doi: https://doi.org/10.1101/481226; this version posted December 4, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license. 93