Evolutionary Genomics of Mycobacterium bovis in Nigerian Cattle and Spillover Host Populations: Reconstructing Transmission and Identifying Intervention Targets

This dissertation reconstructs the evolutionary genomics and transmission history of Mycobacterium bovis in Nigerian cattle and spillover host populations, including humans, goats, and wildlife, using whole genome sequencing and Bayesian phylogenetics to identify the drivers of bovine tuberculosis persistence and rational targets for elimination. Bovine tuberculosis remains uncontrolled in Nigeria despite decades of test-and-slaughter policy, and the genomic basis for M. bovis diversity, transmission networks, and host spillover in Nigeria is entirely uncharacterised, representing a foundational knowledge gap. The dissertation employs a cross-sectional sampling design with longitudinal herd-level follow-up, collecting M. bovis isolates from SICTT-positive cattle, goats, and suspected human contacts across 60 farms in the North Central, North West, and South South geopolitical zones over three years. Whole genome sequencing using Illumina and long-read nanopore platforms is performed on 250 isolates. Bayesian phylodynamic reconstruction using BEAST2 estimates divergence dates, geographic spread patterns, and host-switching events. Drug resistance mutations are catalogued against all first and second-line anti-tuberculosis drugs. The dissertation proposes the Nigerian M. bovis Genomic Lineage Classification (NMGLC) as an original taxonomic contribution, identifying four phylogenetically distinct lineages with different geographic ranges and host breadths. Original contributions include the M. bovis WGS reference panel, the NMGLC, and a rational intervention target analysis prioritising the three principal transmission bottlenecks identified by network analysis. Keywords: Mycobacterium bovis, whole genome sequencing, phylodynamics, bovine tuberculosis, Nigeria.