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

PLoS Pathog. 2018 May 10;14(5):e1006997. doi: 10.1371/journal.ppat.1006997. eCollection 2018 May.

Abstract

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.

Publication types

  • Historical Article
  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA, Bacterial / genetics
  • DNA, Bacterial / history
  • Europe / epidemiology
  • Evolution, Molecular
  • Genetic Variation
  • Genome, Bacterial
  • History, Medieval
  • Host-Pathogen Interactions / genetics
  • Humans
  • Leprosy / epidemiology
  • Leprosy / history*
  • Leprosy / microbiology
  • Mycobacterium leprae / classification
  • Mycobacterium leprae / genetics*
  • Mycobacterium leprae / pathogenicity
  • Phylogeny
  • Phylogeography
  • Polymorphism, Single Nucleotide

Substances

  • DNA, Bacterial

Grants and funding

This work is supported by the Fondation Raoul Follereau (S.TC.), the Swiss National Science Foundation grant IZRJZ3_164174 (S.T.C), the EMBO short-term fellowship (C.A), and the DFG Graduate School Human Development in Landscapes at Kiel University (B.K.-K., M.B., A.N.), the European Research Council (J.K.), the Max Planck Society (J.K.) and the Hungarian NKFIH Grant K125561(G.P., E.M.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.