Institute of Evolutionary Medicine, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland.
Institute for Archaeological Sciences, University of Tübingen, Rümelinstrasse 19-23, 72070, Tübingen, Germany.
BMC Biol. 2021 Oct 5;19(1):220. doi: 10.1186/s12915-021-01120-2.
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.
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.
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.
麻风病（汉森病）在中世纪的欧洲广泛流行，如今主要在热带和亚热带地区流行，每年报告约 20 万例新病例。尽管它有着悠久的历史和在历史记录中的出现，但它的起源和过去的传播模式仍然知之甚少。应用古代 DNA 方法研究其主要病原体麻风分枝杆菌，可以显著提高我们对这种疾病复杂历史的认识。以前的研究已经确定了在过去的 1500 年里，病原体的遗传连续性很高，并且自中世纪早期以来，至少有四个麻风分枝杆菌谱系存在于欧洲的一些地区。
在这里，我们重建了 19 个古代麻风分枝杆菌基因组，以进一步研究欧洲麻风分枝杆菌的遗传变异，专门关注以前未研究过的地区（白俄罗斯、伊比利亚半岛、俄罗斯、苏格兰）、同一地区的多个地点（英格兰剑桥郡）和两个伊比利亚麻风病院的细菌基因组。总体而言，我们的数据证实了欧洲各地存在相似的系统地理学模式，包括麻风病院的高多样性。此外，我们在白俄罗斯发现了一个新的基因型。通过将完整的古代麻风分枝杆菌基因组数量增加一倍，我们的结果提高了我们对过去麻风分枝杆菌系统地理学的认识，并揭示了欧洲中世纪麻风病院中特别高的麻风分枝杆菌多样性。
我们的发现使我们能够在整个欧洲检测到类似的菌株多样性模式，其中分支 3 是最常见的分支，而麻风病院是多样性高的中心。我们的系统发育树的分辨率更高，也使我们更好地了解了红松鼠和人类之间的种间转移，指出了晚古/中世纪的传播。此外，根据我们对过去麻风分枝杆菌种群多样性的新估计，我们首次了解了这种疾病与罗马扩张或定期跨大西洋长途贸易开始等重大历史事件相关的全球历史。总之，我们的研究结果强调了在全球范围内研究古代麻风分枝杆菌基因组如何提高我们对麻风病全球历史的认识，并有助于当前麻风分枝杆菌全球传播模型的建立，包括种间传播。
