Fishing just isn’t what it used to be, and neither is DNA sequencing. Reconstructing the ancient plague genome required the development of new technology that was able to enrich the sequencing sample by concentrating the Y. pestis sequence fragments from the brew of human DNA and contaminants in all aDNA extracts.
Using an Agilent Capture Array (above), a large international group led by Johannas Krause and Hendrik Poinar [1] fished ancient, degraded fragments of Yersinia pestis out of bone and teeth extracts from the East Smithfield Black Death cemetery using lures (probes) composed of short fragments of a modern Y. pestis strain. These lures (probes) are attached to the slide and the extracts are washed over the slide. Complementary ancient fragments in the extract will hybridize with the single stranded probes while the remainder of the extract is washed away. (The match does not have to be exact for these probes to hang on to the extract fragment allowing them to pull out fragments with minor sequence variants.) The fragments can then be released from the slide and sequenced. Using two of these slides (one in Canada and one in Germany?) they captured over two million unique fragments. Overlapping regions of sequence were lined up to reconstruct “93.48% of the targeted regions” (complementary to the modern CO92 strain of Yersinia pestis). All genes of the modern Y. pestis strains appear to be accounted for, although the existence of any part of the ancient genome that is completely foreign to modern strains can not be ruled out.
When they analyzed the ancient sequence they found that it is surprisingly similar to modern Y. pestis strains. It differed from modern strains at only 97 positions all of which matched the ancestral genes from Yersinia psuedotuberculosis. The most important information in this paper is that the genes of the Black Death clones do not have significant genetic differences that would make the ancient clone(s) more virulent than modern strains.
They also went on to place their reconstructed genome on the phylogenetic tree of Y. pestis relative to public sequences of modern Y. pestis strains. They placed the East Smithfield Black Death clone at the node where modern Y. pestis strains branch from the ancestral stem leading to Yersinia pseudotuberculosis, its parent species. Actually it is the primary East Smithfield clone because they also found another derivative clone in the extracts from only four people at East Smithfield. Placing the Black Death strain at the branch point is basically the same finding as Haenesh et al, 2010 [2] that I’ve discussed in a previous post. Apart from having much more sequence to compare, the finding really isn’t new. It also doesn’t really tell us anything new about the earlier, first pandemic known as the Plague of Justinian. Despite their assertion that the Plague of Justianian was “distinct from all currently circulating strains commonly associated with human infections, or it was another disease all together” [1], they can not rule out that the Black Death strain itself is not identical to or a descendant of the Justinian strain. I see no reason to think that it was another disease. Two previous groups, Drancourt’s group in Marseille [3] and Wiechmann and Grupe in Bavaria [4], have found Yersinia pestis in 6th century remains. Further, the speed, virulence, and signs and symptoms of the Plague of Justinian match descriptions of the Black Death.
The similarity of the Black Death strain with modern Yersinia pestis strains validates modern public health and biosecurity concerns over the plague. Although this ancient strain would be susceptible to modern antibiotics — if they are administered in time, we will need all the information we can get for a potential arms race with the plague.
[1] Bos, K., Schuenemann, V., Golding, G., Burbano, H., Waglechner, N., Coombes, B., McPhee, J., DeWitte, S., Meyer, M., Schmedes, S., Wood, J., Earn, D., Herring, D., Bauer, P., Poinar, H., & Krause, J. (2011). A draft genome of Yersinia pestis from victims of the Black Death Nature DOI: 10.1038/nature10549
[2] Haensch, S., Bianucci, R., Signoli, M., Rajerison, M., Schultz, M., Kacki, S., Vermunt, M., Weston, D., Hurst, D., Achtman, M., Carniel, E., and Bramanti, B. (2010). Distinct clones of Yersinia pestis caused the Black Death. PLoS Pathogens, 6 (10)
[3] Drancourt M, Signoli M, Vu Dang L, Bizot B, Roux V, Tzortzis S, et al. Yersinia pestis Orientalis in remains of ancient plague patients. Emerg Infect Dis [serial on the Internet]. 2007 Feb [date cited]. Available from http://wwwnc.cdc.gov/eid/article/13/2/06-0197.htm
[4] Wiechmann I, & Grupe G (2005). Detection of Yersinia pestis DNA in two early medieval skeletal finds from Aschheim (Upper Bavaria, 6th century A.D.). American journal of physical anthropology, 126 (1), 48-55 PMID: 15386257
Contagions 