Ancient Yersinia pestis genomes lack the virulence-associated YpfΦ prophage present in modern pandemic strains.

Yersinia pestis is the causative agent of at least three major plague pandemics (Justinianic, Medieval and Modern). Previous studies on ancient Y. pestis genomes revealed that several genomic alterations had occurred approximately 5000-3000 years ago and contributed to the remarkable virulence of this pathogen. How a subset of strains evolved to cause the Modern pandemic is less well-understood. Here, we examined the virulence-associated prophage (YpfΦ), which had been postulated to be exclusively present in the genomes of strains associated with the Modern pandemic. The analysis of two new Y. pestis genomes from medieval/early modern Denmark confirmed that the phage is absent from the genome of strains dating to this time period. An extended comparative genome analysis of over 300 strains spanning more than 5000 years showed that the prophage is found in the genomes of modern strains only and suggests an integration into the genome during recent Y. pestis evolution. The phage-encoded Zot protein showed structural homology to a virulence factor of Vibrio cholerae. Similar to modern Y. pestis, we observed phages with a common origin to YpfΦ in individual strains of other bacterial species. Our findings present an updated view on the prevalence of YpfΦ, which might contribute to our understanding of the host spectrum, geographical spread and virulence of Y. pestis responsible for the Modern pandemic.

A millennium of population change in pre-modern Danish Ribe.

Denmark experienced major socioeconomic changes, including overall population growth, during the Viking, medieval and post-medieval periods from ca. AD 800 to 1800. Archaeological skeletons provide a unique perspective on the population structure of Ribe, a Danish town in Jutland, during the millennium that immediately precedes the industrialization of northern Europe. This skeletal study adds temporal depth to our understanding of an overall trend toward longer life as seen from historical records and in modern studies. Adult male and female mean age at death and mortality profiles during three time periods are based on 943 adult skeletons from three urban cemeteries that collectively represent a cross-section of this urban community. For both males and females, the mean age at death decreased slightly from the Viking (males 38.5 years, females 38.6 years) to the medieval (males 37.4 years, females 36.9 years) periods. This decline was followed by an increase in mean age at death for both sexes from the medieval to post-medieval (males 40.4 years, females 43.2 years) periods, a notable gain of 3.0 and 6.3 years for men and women, respectively.

The association between skeletal lesions and tuberculosis diagnosis using a probabilistic approach.

Sensitivity and specificity estimates for 18 skeletal lesions were generated from modern skeletons for future paleoepidemiological analyses of tuberculosis prevalence in archaeological samples. A case-control study was conducted using 480 skeletons from 20th century American skeletal collections. One-half of the skeletons were documented tuberculosis cases (Terry Collection). The remaining age and sex-matched skeletons were controls (Bass Collection). The association between 18 candidate skeletal lesions and tuberculosis was established by comparing lesion distributions in case and control groups. Lesion indicators at six locations - visceral surface of ribs, ventral vertebral bodies, lateral part of ilium, acetabular fossa, iliac auricular surface, and ulna olecranon process - occurred significantly more often among cases than in controls, and were associated with one another. The most useful indicator proved to be a bony reaction on ventral thoracic and lumbar vertebral bodies. Its presence means a 53.3% probability of a true tuberculosis diagnosis. Because of the nature of the reference sample - 20th century American cases - sensitivity and specificity estimates will better estimate disease prevalence in archaeological samples from cultural settings where pulmonary tuberculosis predominated. The general approach of this proof-of-concept study is applicable to other diseases that occur commonly and affect bone.

Tuberculosis in medieval and early modern Denmark: A paleoepidemiological perspective.

Millions of people worldwide have sickened and died from tuberculosis in recent centuries. Yet for most of human existence, the impact of tuberculosis on society is largely unknown. It is, indeed, unknowable without methods suitable for estimating disease prevalence in skeletal samples. Here such a procedure is applied to medieval and early modern Danish skeletons, and it shows how disease prevalence varied with differences in socioeconomic conditions. The approach is based on sensitivity and specificity estimates from modern skeletons. To augment our understanding of tuberculosis in Danish history, 713 adult skeletons were examined, all from Ribe. Tuberculosis increased from 17% to 40% in the medieval to early modern periods in Ribe. Low status (29%) people were more likely to contract the disease than those of high status (10%). The general model, derived from the modern expression of tuberculosis, fits the early modern sample better than it does the medieval skeletons. Differences in the model's fit indicate the skeletal expression changed over time. Notably, rib lesions increased in frequency from the medieval to early modern periods. The approach developed here can provide insights into host-pathogen relationships and disease expression in future work with tuberculosis and other diseases that affect the skeleton.

Ancient genomes reveal a high diversity of Mycobacterium leprae in medieval Europe.

Studying ancient DNA allows us to retrace the evolutionary history of human pathogens, such as Mycobacterium leprae, the main causative agent of leprosy. Leprosy is one of the oldest recorded and most stigmatizing diseases in human history. The disease was prevalent in Europe until the 16th century and is still endemic in many countries with over 200,000 new cases reported annually. Previous worldwide studies on modern and European medieval M. leprae genomes revealed that they cluster into several distinct branches of which two were present in medieval Northwestern Europe. In this study, we analyzed 10 new medieval M. leprae genomes including the so far oldest M. leprae genome from one of the earliest known cases of leprosy in the United Kingdom-a skeleton from the Great Chesterford cemetery with a calibrated age of 415-545 C.E. This dataset provides a genetic time transect of M. leprae diversity in Europe over the past 1500 years. We find M. leprae strains from four distinct branches to be present in the Early Medieval Period, and strains from three different branches were detected within a single cemetery from the High Medieval Period. Altogether these findings suggest a higher genetic diversity of M. leprae strains in medieval Europe at various time points than previously assumed. The resulting more complex picture of the past phylogeography of leprosy in Europe impacts current phylogeographical models of M. leprae dissemination. It suggests alternative models for the past spread of leprosy such as a wide spread prevalence of strains from different branches in Eurasia already in Antiquity or maybe even an origin in Western Eurasia. Furthermore, these results highlight how studying ancient M. leprae strains improves understanding the history of leprosy worldwide.