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Abstract
Mycobacterium bovis is an intracellular pathogen that causes bovine tuberculosis. The bacterium has been shown to infect a wide host range of mammalian species including domestic animals, wild animals, and even humans. M. bovis researchers have utilized genotyping techniques to discriminate isolates found during outbreaks, but the advent of Next Generation Sequencing has now led to the ability to gain high level resolution on transmission through the use of single nucleotide polymorphism (SNP) sites. While SNP identification helps elucidates transmission routes, the genomic signatures and variations that promote adaptation of M. bovis across different environments and organizational scales, alongside the role of other genomic factors in the M. bovis transmission process are understudied problems. My work presented here looks to utilize computational approaches to elucidate the genomic variations that could prove useful in discrimination of M. bovis across organizational scales. First, I developed a bioinformatic platform titled mbovpan to compute and visualize M. bovis genomic variation. Using mbovpan, I was able to analyze M. bovis data sequenced from Woodchester Park, United Kingdom to investigate the difference between M. bovis accessory genes in isolates extracted from cattle and badgers. Next, I used M. bovis sequences collected from 700 hosts across three countries (United Kingdom, United States, and New Zealand) to investigate the relationship between high SNP density and/or selective sweep sites and different environments (e.g., at the host-species, geographical, and/or sub-population levels). Finally, I inferred the M. bovis pangenome of a global dataset of isolates in order to determine the genome diversity across different organization scales such as host species, geographical location and genomic population clusters. My results showcased that the accessory genome evolved independently of geographic or host separation, and that the clustering of the accessory genes was dependent on a small number of genes that had pathogenic functions or were impacted by sequence altering indel mutations. As for the core genome, M. bovis lineage and genomic population clustering remained intact when overlaid on maximum likelihood phylogenies, but the amount of genomic similarity present within the M. bovis lineages appears to be imbalanced.