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. 2018 Jun 8;9(1):2234.
doi: 10.1038/s41467-018-04550-9.

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

Maria A Spyrou  1   2 , Rezeda I Tukhbatova  3   4 , Chuan-Chao Wang  3   5 , Aida Andrades Valtueña  3 , Aditya K Lankapalli  3 , Vitaly V Kondrashin  6 , Victor A Tsybin  7 , Aleksandr Khokhlov  8 , Denise Kühnert  3   9 , Alexander Herbig  3 , Kirsten I Bos  10 , Johannes Krause  11   12
Affiliations

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

Maria A Spyrou et al. Nat Commun. .

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.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Population genetic analysis to infer the ancestry of RT5. a Geographic location (map purchased from vectormaps.de) and picture of RT5 burial in the Mikhailovsky II site (picture credits to V.V. Kondrashin and V.A. Tsybin). b Principal component analysis (PCA) of modern-day western Eurasian populations (not shown) and projected ancient populations (n = 82, see population labels), including the newly sequenced RT5 individual from Samara and c estimation of ancestral admixture components using ADMIXTURE analysis (K = 12) (see Supplementary Methods)
Fig. 2
Fig. 2
Y. pestis genomic characterisation and maximum likelihood phylogeny. a pMT1 coverage plots made with the Circos software. The plots were constructed to a maximum coverage of three-fold, and average coverage was calculated over 100-bp windows. The presented strains are in the following order starting from the outmost: CO92 pMT1 (reference) in grey, the oldest (RISE509) and youngest (RISE505) isolates from the LNBA lineage are shown in purple, RT5 and RT6 are shown in green, the Iron Age RISE397 isolate is shown in brown, a Justinianic isolate from Altenerding (Germany) is shown in blue and a London Black Death isolate is shown in red. The position of the ymt gene within the pMT1 plasmid is indicated on the plot. b A worldwide dataset of Y. pestis ancient and present-day chromosomal genomes (n = 179) was used to reconstruct the phylogenetic tree, considering 1054 SNP positions (see Supplementary Fig. 3 for a phylogeny using all sites). The main branches were collapsed to enhance the clarity of the phylogeny, and branch lengths are shown as number of substitutions per site. The newly sequenced RT5 strain (green) was included in the phylogeny alongside eight Bronze Age strains belonging to the LNBA lineage (purple), a single Justinianic strain (blue), and nine second pandemic strains (red). Asterisks denote bootstrap values >95 (1000 bootstrap iterations carried out). The two-sigma (95.4%) radiocarbon or archaeological dates of Bronze Age and historical strains are shown. Country or geographical region abbreviations are as follows: CHN (China), USA (United States of America), MDG (Madagascar), IND (India), IRN (Iran), MNM (Myanmar), RUS (Russia), GB (Great Britain), DE (Germany), FRA (France), MNG (Mongolia), NPL (Nepal), FSU (Former Soviet Union), CGO (Congo), UGA (Uganda), LTU (Lithuania), EST (Estonia) and CRO (Croatia). See also Supplementary Fig. 4 for the inferred phylogenetic positioning of RISE397. c Timeline spanning radiocarbon and archaeological dates, from which Y. pestis genomic data have been included in this study. Points on the timeline indicate median dates
Fig. 3
Fig. 3
Heat map of coverage across virulence-associated genes. The virulence potential of RT5 shotgun-sequenced and captured genomes is compared to representative strains from the LNBA lineage, namely, RISE509 (whose virulence profile is identical to that of isolates RK1.001, GEN72, Gyvakarai1 and Kunila2) and 1343UnTal85 (whose virulence profile is identical to 6Postillionstrasse and RISE505). In addition it is compared to modern-isolate representatives 0.PE4-Microtus91001, 0.PE2-PestoidesF and 1.OR1-CO92, and to Y. pseudotuberculosis (strain IP32953). The virulence factors inspected were located on the Y. pestis chromosome, as well as on the pMT1, pPCP1 and pCD1 plasmids. The percentage of each gene covered (scale bar) was computed and plotted in the form of a heatmap using the ggplot2 package in R
See this image and copyright information in PMC

References

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