A draft genome of Yersinia pestis from victims of the Black Death

Journal name: Nature
Year published: (2011)
DOI: doi:10.1038/nature10549
Received 25 July 2011
Accepted 09 September 2011
Published online 12 October 2011

Technological advances in DNA recovery and sequencing have drastically expanded the scope of genetic analyses of ancient specimens to the extent that full genomic investigations are now feasible and are quickly becoming standard¹. This trend has important implications for infectious disease research because genomic data from ancient microbes may help to elucidate mechanisms of pathogen evolution and adaptation for emerging and re-emerging infections. Here we report a reconstructed ancient genome of Yersinia pestis at 30-fold average coverage from Black Death victims securely dated to episodes of pestilence-associated mortality in London, England, 1348–1350. Genetic architecture and phylogenetic analysis indicate that the ancient organism is ancestral to most extant strains and sits very close to the ancestral node of all Y. pestis commonly associated with human infection. Temporal estimates suggest that the Black Death of 1347–1351 was the main historical event responsible for the introduction and widespread dissemination of the ancestor to all currently circulating Y. pestis strains pathogenic to humans, and further indicates that contemporary Y. pestis epidemics have their origins in the medieval era. Comparisons against modern genomes reveal no unique derived positions in the medieval organism, indicating that the perceived increased virulence of the disease during the Black Death may not have been due to bacterial phenotype. These findings support the notion that factors other than microbial genetics, such as environment, vector dynamics and host susceptibility, should be at the forefront of epidemiological discussions regarding emerging Y. pestis infections.

Figures at a glance

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Figure 1: Coverage plots for genomic regions sequenced.

a, c–e, Coverage plots for the chromosome (a) and the plasmids pMT1 (c), pCD1 (d) and pPCP (e). Coverage in blue, GC content in green. Scale lines indicate 10-, 20-, 30-, 40- and 50-fold coverage and 10%, 20%, 30%, 40% and 50% GC content. For plasmids, red corresponds to coding regions, yellow to mobile elements. Chromosome shows median coverage per gene. Plasmids show each site plotted. Coverage distributions for the plasmids are shown in Supplementary Fig. 5. b, Distributions show chromosomal coverage of array 1 (blue) and array 2 (red), indicating that deeper sequencing increases the number of reads per site, but does not substantially influence overall coverage.
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Figure 2: Alignment of mapped reconstructed contigs against CO92 and Microtus genomes.

Reads mapped at positions A (blue) and B (green) are 231 kb apart in the linearized CO92 genome. Adjacent sequence is high coverage although only 18× and 20× is shown due to space constraints (black) for A and B, respectively. The structural variant was assembled using reads that did not map to CO92 (red). Its position is shown on the linearized Microtus 91001 chromosome where the 9,096 bp contig maps with 100% identity.
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Figure 3: Phylogenetic placement and historical context for the East Smithfield strain.

a, Median network of ancient and modern Y. pestis based on 1,694 variant positions in modern genomes¹⁴. Coloured circles represent different clades as defined in ref. 13. Gray circles represent hypothetical nodes. b, Phylogenetic tree using 1,694 variable positions. Divergence time intervals are shown in calendar years, with neighbour-joining bootstrap support (blue italic) and Bayesian posterior probability (blue). Grey box indicates known human pathogenic strains. A, NZ ACNQ01000; Nepal516, NC 008149; KIM10, NC 004088; B, NZ AAYT01000; C, NZ ABAT01000; D, NZ ACNS01000; E, NZ AAYS01000; F, NZ AAOS02000; CO92, NC 003143; G, NZ ABCD01000; H, NZ AAYV01000; I, NC 014029; J, NZ AAYR01000; Antiqua, NC 008150. c, Geographical origin of genome sequences used in a and b. d, Geographical spread of the Black Death from infection routes reported in ref. 4.
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