Mycobacterium leprae diversity and population dynamics in medieval Europe from novel ancient genomes

Abstract

Background Hansen’s disease (leprosy), widespread in medieval Europe, is today mainly prevalent in tropical and subtropical regions with around 200,000 new cases reported annually. Despite its long history and appearance in historical records, its origins and past dissemination patterns are still widely unknown. Applying ancient DNA approaches to its major causative agent, Mycobacterium leprae, can significantly improve our understanding of the disease’s complex history. Previous studies have identified a high genetic continuity of the pathogen over the last 1500 years and the existence of at least four M. leprae lineages in some parts of Europe since the Early Medieval period. Results Here, we reconstructed 19 ancient M. leprae genomes to further investigate M. leprae’s genetic variation in Europe, with a dedicated focus on bacterial genomes from previously unstudied regions (Belarus, Iberia, Russia, Scotland), from multiple sites in a single region (Cambridgeshire, England), and from two Iberian leprosaria. Overall, our data confirm the existence of similar phylogeographic patterns across Europe, including high diversity in leprosaria. Further, we identified a new genotype in Belarus. By doubling the number of complete ancient M. leprae genomes, our results improve our knowledge of the past phylogeography of M. leprae and reveal a particularly high M. leprae diversity in European medieval leprosaria. Conclusions Our findings allow us to detect similar patterns of strain diversity across Europe with branch 3 as the most common branch and the leprosaria as centers for high diversity. The higher resolution of our phylogeny tree also refined our understanding of the interspecies transfer between red squirrels and humans pointing to a late antique/early medieval transmission. Furthermore, with our new estimates on the past population diversity of M. leprae, we gained first insights into the disease’s global history in relation to major historic events such as the Roman expansion or the beginning of the regular transatlantic long distance trade. In summary, our findings highlight how studying ancient M. leprae genomes worldwide improves our understanding of leprosy’s global history and can contribute to current models of M. leprae’s worldwide dissemination, including interspecies transmissions.

Historic and Prehistoric Epidemics: An Overview of Sources Available for the Study of Ancient Pathogens

“…It runs a chronic, slow course, leaving sufficient time to bury the dead peacefully in cemeteries within the institution. Ancient DNA analysis of remains from medieval European leprosaria, resulted in retrieval of partial and complete genomes of M. leprae, with surprisingly high genetic diversity [55][56][57]. Complete M. leprae genomes had likewise been retrieved from bones collected from a 10th-12 th century British leprosarium [58], confirming that dedicated hospital sites are fertile hunting grounds for research on pathogen evolution.…”

Pathogen genomics study of an early medieval community in Germany reveals extensive co-infections

“…Two British strains dating to a similar time period were included in the phylogenetic analysis (GC96, fifth–sixth century and EDI006, sixth–seventh century CE). The Lauchheim strain groups in branch 3 together with both British strains, suggesting low diversity of M. leprae in the Early Medieval Period [ 23 ]. Based on the observed variation (Fig.…”

“…S7), we can hypothesize an early appearance of branch 3 strains in Europe. The spread may have been facilitated by the expanding Roman Empire [ 22 , 23 ].…”

“…5 ), which were to dominate the later epidemic (Additional file 1 : Fig. S7) [ 23 ]. Taken together, we would like to hypothesize that LALIA may have created an ecological context in which persistent outbreaks set the stage for severe epidemics hundreds of years later.…”

The immunogenetic impact of European colonization in the Americas

“…Ancient sequences of M. leprae have revealed high strain conservation, low mutation rate, and no discernible reduction in virulence compared to modern strains, observed across Europe. From this, it has been hypothesized that the 16th-century decline in European leprosy cases may be explained by selective changes in European host immunity, possibly allowing more recent populations to better combat the detrimental effects of M. leprae infection (Schuenemann et al, 2018;Pfrengle et al, 2021). However, the specific mechanisms through which selection putatively acted remain unknown, with the perceived reduction in European incidence/lethality possibly caused by non-selective, random evolutionary forces.…”