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. 2019 Jun 18;116(25):12363-12372.
doi: 10.1073/pnas.1820447116. Epub 2019 Jun 4.

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

Marcel Keller  1   2 , Maria A Spyrou  3 , Christiana L Scheib  4   5 , Gunnar U Neumann  3 , Andreas Kröpelin  3   6 , Brigitte Haas-Gebhard  7 , Bernd Päffgen  8 , Jochen Haberstroh  9 , Albert Ribera I Lacomba  10 , Claude Raynaud  11 , Craig Cessford  4 , Raphaël Durand  12 , Peter Stadler  13 , Kathrin Nägele  3 , Jessica S Bates  4 , Bernd Trautmann  2 , Sarah A Inskip  14 , Joris Peters  2   15   16 , John E Robb  4 , Toomas Kivisild  4   17 , Dominique Castex  18 , Michael McCormick  19   20 , Kirsten I Bos  3 , Michaela Harbeck  21 , Alexander Herbig  1 , Johannes Krause  1   20
Affiliations

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

Marcel Keller et al. Proc Natl Acad Sci U S A. .

Abstract

The first historically documented pandemic caused by Yersinia pestis began as the Justinianic Plague in 541 within the Roman Empire and continued as the so-called First Pandemic until 750. Although paleogenomic studies have previously identified the causative agent as Y. pestis, little is known about the bacterium's spread, diversity, and genetic history over the course of the pandemic. To elucidate the microevolution of the bacterium during this time period, we screened human remains from 21 sites in Austria, Britain, Germany, France, and Spain for Y. pestis DNA and reconstructed eight genomes. We present a methodological approach assessing single-nucleotide polymorphisms (SNPs) in ancient bacterial genomes, facilitating qualitative analyses of low coverage genomes from a metagenomic background. Phylogenetic analysis on the eight reconstructed genomes reveals the existence of previously undocumented Y. pestis diversity during the sixth to eighth centuries, and provides evidence for the presence of multiple distinct Y. pestis strains in Europe. We offer genetic evidence for the presence of the Justinianic Plague in the British Isles, previously only hypothesized from ambiguous documentary accounts, as well as the parallel occurrence of multiple derived strains in central and southern France, Spain, and southern Germany. Four of the reported strains form a polytomy similar to others seen across the Y. pestis phylogeny, associated with the Second and Third Pandemics. We identified a deletion of a 45-kb genomic region in the most recent First Pandemic strains affecting two virulence factors, intriguingly overlapping with a deletion found in 17th- to 18th-century genomes of the Second Pandemic.

Keywords: Anglo-Saxons; Justinianic Plague; Merovingians; ancient DNA; bacterial evolution.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.
Fig. 1.
Geographic extent of the First Pandemic and sampled sites. (A) Map of historically documented occurrences of plague (regions shaded, cities depicted by circles, both with respective years of occurrence) between 541 and 750 in Europe and the Mediterranean basin. All sources are given in SI Appendix. Sites with genomic evidence for Y. pestis are shown as pink (previously published) and yellow squares (presented here). (B) Enlarged rectangular space of A (Right) showing all sites in Germany and Austria that were included in this study. Sites tested negative are depicted in black upward-pointing triangles (burials dating before 541), squares (dating around 541–544), and downward-pointing triangles (dating after 544). (C) Enlarged Inset of A (Left) shows reported occurrences in France and main rivers.
Fig. 2.
Fig. 2.
Phylogenetic tree. (A) Maximum-likelihood tree with full SNP alignment (6,580 positions) of 233 modern Y. pestis and one Y. pseudotuberculosis genome, 10 published (second- to third-century Tian Shan in orange; Altenerding in blue; Second Pandemic in red) and eight genomes presented here (green) with country given in brackets (DEU = Germany, ESP = Spain, FRA = France, GBR = Great Britain, RUS = Russia). Numbers and origins of modern genomes are given in brackets (CHN = China, COG = Congo, FSU = Former Soviet Union, IND = India, IRN = Iran, MDG = Madagascar, MMR = Myanmar, MNG = Mongolia, NPL = Nepal, UGA = Uganda). Numbers on nodes are showing bootstrap values (1,000 iterations). (B) Detailed, manually drawn tree of the First Pandemic genomes showing all remaining SNP positions after SNP evaluation (number of SNPs given in italics). (C) Detailed tree of the 1.ORI clade within branch 1, showing the polytomy.
Fig. 3.
Fig. 3.
Heatmap showing the percentage of coverage of chromosomal virulence factors. First Pandemic genomes (blue and green) and Second Pandemic genomes (red) are shown in combination with selected strains of main clades of modern Y. pestis diversity on branch 0 as well as the reference genomes of Y. pseudotuberculosis and Y. pestis (CO92).
See this image and copyright information in PMC

References

    1. Yang R., Anisimov A., Yersinia pestis: Retrospective and Perspective (Springer, Dordrecht, 2016).
    1. Burki T., Plague in Madagascar. Lancet Infect. Dis. 17, 1241 (2017). - PubMed
    1. Andrades Valtueña A., et al. , The Stone Age plague and its persistence in Eurasia. Curr. Biol. 27, 3683–3691.e8 (2017). - PubMed
    1. Rasmussen S., et al. , Early divergent strains of Yersinia pestis in Eurasia 5,000 years ago. Cell 163, 571–582 (2015). - PMC - PubMed
    1. Spyrou M. A., et al. , Analysis of 3800-year-old Yersinia pestis genomes suggests Bronze Age origin for bubonic plague. Nat. Commun. 9, 2234 (2018). - PMC - PubMed

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