Analysis of Mycobacterium leprae bacteria in leprosy-affected individuals from Anatolian Medieval-Late Ottoman period by using ancient DNA methods

Infectious diseases have historically caused pandemics or epidemics, leading to significant social and genetic changes in human populations. As a result, the history of infectious diseases has attracted the interest of researchers from various disciplines. Leprosy, caused by the bacteria Mycobacterium leprae and Mycobacterium lepromatosis, is a chronic infectious disease that results in various lesions in the peripheral nervous system, skeletal system, and skin surface. It has had a significant impact on populations throughout history, leaving deep traces in their past, especially since the Middle Ages. Although several hypotheses have been proposed, questions regarding the origin and routes of spread of the disease have not yet been fully resolved. This thesis analyzes skeletal samples exhibiting bone changes associated with leprosy, which were obtained from archaeological excavations in Anatolia, namely the İznik Roman Theater (n=1), Salattepe Höyük (n=2), Kovuklukaya (n=5), and Kadıkalesi (n=1). These human remains were examined through an interdisciplinary approach, incorporating both paleopathological and archaeogenomic perspectives. Paleopathological analyzes show that four individuals in the sample set had advanced lesions that are specific to leprosy. Of these, three samples yielded ancient M. leprae DNA, with the genome coverage ranging from 0.64x to 4.19x. Among them, two samples were archaeologically dated to the Byzantine period, and one to the Late Ottoman period. Phylogenetic analysis revealed that the Byzantine period samples clustered with the most ancestral strain type 3K-0, while the Late Ottoman period Salattepe sample was positioned in internal branches along with 2F strains. Considering that the ancient DNA sampling in the literature mostly focused on the European Medieval Era, this thesis provides the contemporary whole genome of M. leprae from outside Europe for the first time. Furthermore, the Salattepe sample from the Late Ottoman period contributes as a representative of Late Modern period samples which are limited in the literature.