02954nas a2200481 4500000000100000008004100001100001800042700001300060700001900073700001200092700001300104700001300117700001400130700001300144700001200157700001600169700001400185700001200199700001500211700001800226700001500244700001400259700001400273700001300287700001500300700001100315700001700326700001400343700001200357700001100369700001500380700001700395700001300412700001400425700001100439700001300450245008800463856007800551300001300629490000700642520180900649022001402458 2018 d1 aSchuenemann V1 aAvanzi C1 aKrause-Kyora B1 aSeitz A1 aHerbig A1 aInskip S1 aBonazzi M1 aReiter E1 aUrban C1 aPedersen DD1 aTaylor MG1 aSingh P1 aStewart GR1 aVelemínsky P1 aLikovsky J1 aMarcsik A1 aMolnár E1 aPálfi G1 aMariotti V1 aRiga A1 aBelcastro GM1 aBoldsen J1 aNebel A1 aMays S1 aDonoghue H1 aZakrzewski S1 aBenjak A1 aNieselt K1 aCole S1 aKrause J00aAncient genomes reveal a high diversity of Mycobacterium leprae in medieval Europe. uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5944922/pdf/ppat.1006997.pdf ae10069970 v143 a

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.

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