In August, researchers provided definitive evidence that Yersinia pestis, which is still causing infections in humans, was the bacteria behind the Black Death, perhaps the most deadly disease outbreak in human history. They managed this by unearthing skeletons from a mass burial site in London and obtaining DNA sequences from the bacteria that killed those interred over 500 years ago. Now, some of the same people are back with a new publication in which they report a draft of the entire genome sequence of the bacteria behind the Black Death.

The new genome is not complete, but it clearly shows that the bacteria found in England are nearly identical to an ancestral species that did not infect humans, and shares common features with all modern strains. The authors conclude that the medieval plague almost certainly introduced Y. pestis to the world, and that some factor other than the bacteria themselves may have been the key to making the plague so deadly.

Their earlier work on samples from the grave site had allowed the authors to identify samples that had preserved relatively high amounts of DNA. To separate out the Y. pestis DNA, they constructed a DNA chip that contains sequences from the modern bacteria; the DNA from the plague bacteria base-paired with the DNA on the chip, allowing it to be separated out from all the other bacterial and human DNA present in the samples. This technique would miss any large insertions or deletions of DNA, but is enough to provide a good draft of the genome (which can allow follow up work to fill in any gaps).

With the DNA they isolated, the authors were able to put over 4.3 million bases (Megabases) into continuous stretches of DNA; only 10 areas showed signs of major rearrangements. Overall, the authors obtained sequence for 93 percent of the genome areas they targeted with their DNA chip. In all those millions of bases, there were only 97 differences between the plague bacteria and a modern strain. Each one of these differences was present in an ancestor, Y. pseudotuberculosis, that does not infect humans. Thus, the plague bacteria is at or very close to the root of the Y. pestis phylogenetic tree.

How close? Given they had a precise date on the use of their burial site (East Smithfield was put into use during the winter of 1348-49), the authors were able to calibrate the phylogenetic tree of the plague bacteria and provide it with a pretty exact timing. The East Smithfield samples were nearly at the root of all Y. pestis strains currently infecting humans. That root was dated as likely to be between 1282 and 1343, with the later date being just a few years before the first appearance of the Black Death in Asia. Thus, the authors conclude that, almost as soon as Y. pestis started to infect humans, it went global, causing a massive pandemic in Europe and the Near East.

This rules out this pathogen when it comes to explaining the cause of the Justinian Plague, which hit Europe about 800 years earlier. If that was Y. pestis as well, then it left no descendants. Alternately, it was a completely different bacteria, and we'll have to wait for someone to find some well-preserved victims.

The other thing that their analysis makes clear is that, in its 600-year history, the species has undergone very little change on the genetic level—most proteins, including ones involved in virulence, are very similar in the East Smithfield strain and modern equivalents. Thus, it's not obvious that anything about the pathogen itself is responsible for the change from a deadly pandemic to a localized hazard that doesn't tend to kill many people.

The authors aren't short of alternative possibilities, though, writing, "we posit that molecular changes in pathogens are but one component of a constellation of factors contributing to changing infectious disease prevalence and severity," with that constellation including, "genetics of the host population, climate, vector dynamics, social conditions, and synergistic interactions with concurrent diseases." Some combination of these, it seems helped turn Y. pestis into a killer.

Nature, 2011. DOI: 10.1038/nature10549 (About DOIs).