Genome-Wide Comparison of Medieval and Modern Mycobacterium leprae
- Verena J. Schuenemann1,*,
- Pushpendra Singh2,*,
- Thomas A. Mendum3,*,
- Ben Krause-Kyora4,*,
- Günter Jäger5,*,
- Kirsten I. Bos1,
- Alexander Herbig5,
- Christos Economou6,
- Andrej Benjak2,
- Philippe Busso2,
- Almut Nebel4,
- Jesper L. Boldsen7,
- Anna Kjellström8,
- Huihai Wu3,
- Graham R. Stewart3,
- G. Michael Taylor3,
- Peter Bauer9,
- Oona Y.-C. Lee10,
- Houdini H.T. Wu10,
- David E. Minnikin10,
- Gurdyal S. Besra10,
- Katie Tucker11,
- Simon Roffey11,
- Samba O. Sow12,
- Stewart T. Cole2,†,
- Kay Nieselt5,†,
- Johannes Krause1,†
- 1Institute for Archaeological Sciences, University of Tübingen, 72070 Tübingen, Germany.
- 2Global Health Institute, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
- 3Department of Microbial and Cellular Sciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford, GU2 7XH Surrey, UK.
- 4Institute of Clinical Molecular Biology, Kiel University, 24105 Kiel, Germany.
- 5Center for Bioinformatics, University of Tübingen, 72076 Tübingen, Germany.
- 6Archaeological Research Laboratory, Stockholm University, SE-106 91 Stockholm, Sweden.
- 7Institute of Forensic, Antropologisk Afdelin, Medicine University of Southern Denmark, 5260 Odense S, Denmark.
- 8Osteoarchaeological Research Laboratory, Department of Archaeology and Classical Studies, Stockholm University, SE-106 91 Stockholm, Sweden.
- 9Institute for Medical Genetics and Applied Genomics, University of Tübingen, 72076 Tübingen, Germany.
- 10School of Biosciences, University of Birmingham, Edgbaston, B15 2TU Birmingham, UK.
- 11Department of Archaeology, University of Winchester, Sparkford Road, SO22 4NR Winchester, UK.
- 12Center for Vaccine Development-Mali, Ministry of Health, Centre National d’Appui à la lutte contre la Maladie–ex-Institut Marchoux, BP 251 Bamako, Mali.
- ↵†Corresponding author. E-mail: johannes.krause{at}uni-tuebingen.de (J.K.); kay.nieselt{at}uni-tuebingen.de (K.N.); stewart.cole{at}epfl.ch (S.T.C.)
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↵* These authors contributed equally to this work.
Leprosy: Ancient and Modern
In medieval Europe, leprosy was greatly feared: Sufferers had to wear bells and were shunned and kept isolated from society. Although leprosy largely disappeared from Europe in the 16th century, elsewhere in the world almost a quarter of a million cases are still reported annually, despite the availability of effective drugs. Schuenemann et al. (p. 179, published online 13 June; see the 14 June News story by Gibbons, p. 1278) probed the origins of leprosy bacilli by using a genomic capture-based approach on DNA obtained from skeletal remains from the 10th to 14th centuries. Because the unique mycolic acids of this mycobacterium protect its DNA, for one Danish sample over 100-fold, coverage of the genome was possible. Sequencing suggests a link between the middle-eastern and medieval European strains, which falls in line with social historical expectations that the returning expeditionary forces of antiquity originally spread the pathogen. Subsequently, Europeans took the bacterium westward to the Americas. Overall, ancient and modern strains remain remarkably similar, with no apparent loss of virulence genes, indicating it was most probably improvements in social conditions that led to leprosy's demise in Europe.
Abstract
Leprosy was endemic in Europe until the Middle Ages. Using DNA array capture, we have obtained genome sequences of Mycobacterium leprae from skeletons of five medieval leprosy cases from the United Kingdom, Sweden, and Denmark. In one case, the DNA was so well preserved that full de novo assembly of the ancient bacterial genome could be achieved through shotgun sequencing alone. The ancient M. leprae sequences were compared with those of 11 modern strains, representing diverse genotypes and geographic origins. The comparisons revealed remarkable genomic conservation during the past 1000 years, a European origin for leprosy in the Americas, and the presence of an M. leprae genotype in medieval Europe now commonly associated with the Middle East. The exceptional preservation of M. leprae biomarkers, both DNA and mycolic acids, in ancient skeletons has major implications for palaeomicrobiology and human pathogen evolution.
- Received for publication 25 March 2013.
- Accepted for publication 28 May 2013.
