The next generation of genetic investigations into the Black Death.

T he study of ancient pathogens from human remains is as fascinating as it is essential for our understanding of past epidemics and human health through the centuries. However, ancient pathogens, such as Yersinia pestis (plague, Black Death) or Mycobacterium tuberculosis (tuberculosis), often do not leave unambiguous pathological lesions in the skeletal remains of their victims. Thus, it is not always straightforward to decide whether or not a long-dead individual was affected by a particular pathogen (1). For this reason, researchers have used ancient DNA (aDNA) techniques to search for genetic signatures of pathogens in human remains. In PNAS, Schuenemann et al. (2) turn this approach upside down. In their analysis of 99 human remains from a London burial site known to be associated with the Black Death epidemic of the mid-14th century (and of 10 control individuals not associated with the epidemic), they do not merely attempt to identify the etiological agent in these human remains but, rather, to reconstruct parts of its genetic code. Their aim is to identify whether changes in the genetic code of the Y. pestis-specific pPCP1 plasmid could be responsible for epidemiological differences between ancient and modern forms of Y. pestis infections. Such differences include symptoms, epidemiology, and time of year of peak mortality (2). Using high-throughput sequencing along with the latest DNA hybridization capture techniques, Schuenemann et al. (2) sequence the complete genome of the pPCP1 plasmid of Y. pestis along with some chromosomal markers and markers associated with the pMT plasmid. They find that the pPCP1 plasmid sequence in the ancient remains are consistent with previously sequenced modern variants and conclude that changes in the genetic code of the plasmid are therefore unlikely to be the cause of the known epidemiological differences between ancient and modern forms of the disease.