The bacteria behind the Black Death has a very unusual history. Its ancestor is an unassuming soil bacterium and the current strains of Yersinia pestis still infects thousands of people annually, but no longer cause the suite of horrifying symptoms associated with the medieval plagues. The radical differences between the two versions, in fact, led some to suggest that we have been blaming the wrong bacteria. Now, researchers have obtained DNA from some of London's plague victims and confirmed that Y. pestis appears to be to blame. But the sequences also suggest that the strains of bacteria we see today may be different from the ones that rampaged through Europe.

What transformed soil bacteria into a human pathogen? One key event seems to have been the fact that it picked up a plasmid, a short, circular piece of DNA that can be copied separately from the rest of the organism's DNA. In the case of Y. pestis, that plasmid contained three key genes: two that helped it kill off competing bacteria, and a third that helped it manipulate the human blood clotting system. So, when presented with the opportunity to obtain the DNA of plague victims, this is the DNA the authors decided to target.

The DNA came from 53 bones and 46 teeth from the East Smithfield, a mass burial site in London that dates to the first appearance of the Black Death in Europe, from 1347-1351. This is a key resource, since the different waves of plague that swept through Europe had somewhat different behavior, suggesting that Y. pestis was already adapting to its human hosts. To serve as controls, the authors obtained bones from a set of 10 human remains that predate the appearance of the plague.

To figure out the degree of contamination, each of the sets of bones were used to search for the DNA of human mitochondria, which should provide a degree of information about the levels of damage and contamination. Some of the samples contained no DNA, but a significant number did. Contamination levels were manageable, and the sequence had the sorts of changes that are typical for older, damaged DNA. With the samples looking good, the authors turned to sequencing the Y. pestis plasmid DNA.

As an added layer of precaution, they sent their samples to two different sequencing facilities, neither of which had previously handled Y. pestis DNA. It was relatively easy to pick up plasmid DNA from the tooth samples, which the authors explain as being derived from the pulp, which is rich in the blood vessels that the bacteria prefer to inhabit. The DNA they obtained also showed indications of the same changes seen in the human sequence, indicating it was also likely to be old and have suffered the same damage over time. With sufficient sequences (they got as many as 37,000 from a single sample), they were able to reconstruct the sequence of the plasmid.

For the most part, the sequence is similar to that found in modern strains of the bacteria. In contrast, some of the DNA they obtained from the bacteria's chromosome showed some distinct differences, none of which are present in modern strains. Nevertheless, the sequence was clearly still from Y. pestis.

The authors conclude that this provides a clear indication that a single type of bacteria has been responsible for the Black Death and several other plague outbreaks, and is still causing modern diseases. For some of the parties involved, this is a bit of an about-face, one that was handled with a degree of candor that's rare in scientific publications.

"Two of the authors (SW and JM) have previously argued that the epidemiology, virulence, and population dynamics of the Black Death were too different from those factors of modern yersinial plague to have been caused by Y. pestis," said the paper. "Given the growing body of evidence implicating this bacterium as responsible for the pandemic, we believe scientific debates should now shift to addressing the genetic basis of the epidemic’s unique characteristics."

This work is actually an important step in that shift, even though it's a negative result. The fact that this plasmid is not significantly different from the one carried by modern strains indicates the differences must reside elsewhere, and the initial sequencing of the bacteria's chromosome suggests that more work should be devoted to that. Chromosomes are quite a bit larger than a plasmid, though, and are likely to have many changes scattered across the DNA. Identifying which ones influence the bacteria's lethality could prove a serious challenge even if we can obtain the entire sequence.

PNAS, 2011. DOI: 10.1073/pnas.1105107108 (About DOIs).