Human and mycobacterial coevolution: The role of genetic recombination in reconstructing the evolutionary history of these important human pathogens

Tuberculosis (TB) and leprosy are ancient human diseases, as demonstrated by an abundant osteoarchaeological record and by molecular analyses of prehistoric and historic human remains affected by the disease. Unfortunately, mycobacterial infections (which include TB and leprosy) are not diseases of the past. Today, mycobacteria are still an enormous burden to humans, with an estimated two billion individuals currently being affected by the disease (in a latent or active stage) worldwide. It has become clear that these successful human pathogens can rapidly adapt to their changing environment and host. Evolutionary theory provides an excellent framework to test hypotheses that aim to explain how these pathogens are able to sustain such changes. Understanding the evolutionary mechanisms of the genus Mycobacterium will improve our understanding, and perhaps our ability to control, the processes that yield to these pathogens' evolution and acquisition of drug resistance. Among these adaptive mechanisms, recombination is without doubt an effective way to acquire foreign genetic material into the mycobacterial genome. The scientific community has not reached a consensus on the occurrence of recombination in the genus Mycobacterium.This dissertation aimed to screen a data set comprising 2354 homologous genome sections from publicly available mycobacterial sequences representing 18 strains from 13 species for the occurrence of recombination. Homologous genomic sets were aligned and concatenated in the chromosomal order of one mycobacterial reference species. The concatenated sequence was screened for recombination using a variety of statistical methods, with each event being evaluated by comparing maximum likelihood phylogenies of each recombinant section with the non-recombining portion of the dataset. Incongruent phylogenies were identified by comparing the site-wise log-likelihoods of each tree using multiple tests. The analyses described here indicate that the hypothesis of recombination in mycobacterial homologues cannot be rejected. While an analysis of non-homologous mycobacterial regions will be required to assess the occurrence of non-homologous recombination, this study shows that we cannot assume mycobacterial clonality, even in homologous genomic sections.