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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,<jats:italic>Mycobacterium leprae<\/jats:italic>, can significantly improve our understanding of the disease\u2019s complex history. Previous studies have identified a high genetic continuity of the pathogen over the last 1500\u2009years and the existence of at least four<jats:italic>M. leprae<\/jats:italic>lineages in some parts of Europe since the Early Medieval period.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Here, we reconstructed 19 ancient<jats:italic>M. leprae<\/jats:italic>genomes to further investigate<jats:italic>M. leprae\u2019s<\/jats:italic>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<jats:italic>M. leprae<\/jats:italic>genomes, our results improve our knowledge of the past phylogeography of<jats:italic>M. leprae<\/jats:italic>and reveal a particularly high<jats:italic>M. leprae<\/jats:italic>diversity in European medieval leprosaria.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>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<jats:italic>M. leprae<\/jats:italic>, we gained first insights into the disease\u2019s 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<jats:italic>M. leprae<\/jats:italic>genomes worldwide improves our understanding of leprosy\u2019s global history and can contribute to current models of<jats:italic>M. leprae<\/jats:italic>\u2019s worldwide dissemination, including interspecies transmissions.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s12915-021-01120-2","type":"journal-article","created":{"date-parts":[[2021,10,5]],"date-time":"2021-10-05T13:16:30Z","timestamp":1633439790000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Mycobacterium leprae diversity and population dynamics in medieval Europe from novel ancient genomes"],"prefix":"10.1186","volume":"19","author":[{"given":"Saskia","family":"Pfrengle","sequence":"first","affiliation":[]},{"given":"Judith","family":"Neukamm","sequence":"additional","affiliation":[]},{"given":"Meriam","family":"Guellil","sequence":"additional","affiliation":[]},{"given":"Marcel","family":"Keller","sequence":"additional","affiliation":[]},{"given":"Martyna","family":"Molak","sequence":"additional","affiliation":[]},{"given":"Charlotte","family":"Avanzi","sequence":"additional","affiliation":[]},{"given":"Alena","family":"Kushniarevich","sequence":"additional","affiliation":[]},{"given":"N\u00faria","family":"Montes","sequence":"additional","affiliation":[]},{"given":"Gunnar U.","family":"Neumann","sequence":"additional","affiliation":[]},{"given":"Ella","family":"Reiter","sequence":"additional","affiliation":[]},{"given":"Rezeda I.","family":"Tukhbatova","sequence":"additional","affiliation":[]},{"given":"Nataliya Y.","family":"Berezina","sequence":"additional","affiliation":[]},{"given":"Alexandra P.","family":"Buzhilova","sequence":"additional","affiliation":[]},{"given":"Dmitry S.","family":"Korobov","sequence":"additional","affiliation":[]},{"given":"Stian","family":"Suppersberger Hamre","sequence":"additional","affiliation":[]},{"given":"Vitor M. 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In addition, for the samples processed in Cambridge (UK), all are over 100\u2009years of age and therefore are not subject to the Human Tissue Act (2004). The samples were provided under agreements on scientific collaboration with relevant people linked to the following skeletal collections, who all fully support this study and are listed in the acknowledgments: Edix Hill (Barrington A), Cambridgeshire; Church End, Cherry Hinton, Cambridgeshire; The Hospital of St John the Evangelist, Cambridge; The Nonneseter site, Bergen, Norway; St Mary\u2019s Church, Kirk Hill, Scotland; Valle da Gafaria, Lagos, Portugal leprosarium; Cordi\u00f1anes de Valde\u00f3n, Le\u00f3n, Spain; Studenka necropolis, Mahileu region, Belarus; The Hospital of Sant Ll\u00e0tzer, Barcelona, Spain; Blokhuizen, The Netherlands; Santar\u00e9m, Portugal; Beja leprosarium, Beja, Ermida de Santo Andr\u00e9; D.G. Rokhlin Collection, Moscow, Russia. We also followed guidance for the ethical treatment of human remains following BABAO ().","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"220"}}