The complete genome sequence of Mycobacterium bovis has been determined and compared with those of Mycobacterium tuberculosis and Mycobacterium leprae. The M. bovis genome is >99.95% identical to that of M. tuberculosis, but has a reduced size due to deletions of genetic information. Comparison with M. leprae reveals common gene losses, suggesting the removal of functional redundancy. Cell wall components and secreted proteins show the greatest variation, indicating their potential role in host-bacillus interactions or immune evasion. There are no genes unique to M. bovis, implying that differential gene expression may be the key to the host tropisms of human and bovine bacilli. The genome sequence offers major insight into the evolution, host preference, and pathobiology of M. bovis. M. bovis is the causative agent of tuberculosis in a range of animal species and humans, with significant economic losses to agriculture. It is also the progenitor of the BCG vaccine strain. The genome sequence of M. bovis AF2122/97 is 4,345,492 bp in length, arranged in a single circular chromosome with an average G + C content of 65.63%. The genome contains 3,952 genes, including a prophage and 42 IS elements. The genome is >99.95% identical to that of M. tuberculosis at the nucleotide level, showing colinearity and no evidence of extensive translocations, duplications or inversions. The genome sequence reveals that M. bovis has undergone significant deletions, with only one locus, TbD1, unique to it. Comparison with M. tuberculosis shows 2,437 SNPs between M. bovis and M. tuberculosis H37Rv, and 2,423 SNPs with M. tuberculosis CDC1551. These SNPs are responsible for distinctive characteristics of the bovine bacillus, such as resistance to pyrazinamide. The genome sequence also shows variation in genes encoding cell wall and secreted proteins, which may play a role in host interactions or immune evasion. The genome sequence of M. bovis provides insights into the evolution, host preference, and pathobiology of the organism. It also highlights the importance of gene expression and cell envelope components in the adaptation of M. bovis to different hosts. The genome sequence has implications for the development of new control strategies for bovine tuberculosis, as well as for the understanding of the pathogenesis of tuberculosis in humans. The sequence also reveals that M. bovis has undergone significant genome downsizing, with many genes either deleted or inactivated, suggesting that the loss of genes may be a key factor in the adaptation of the organism to different hosts. The genome sequence of M. bovis is a valuable resource for understanding the biology ofThe complete genome sequence of Mycobacterium bovis has been determined and compared with those of Mycobacterium tuberculosis and Mycobacterium leprae. The M. bovis genome is >99.95% identical to that of M. tuberculosis, but has a reduced size due to deletions of genetic information. Comparison with M. leprae reveals common gene losses, suggesting the removal of functional redundancy. Cell wall components and secreted proteins show the greatest variation, indicating their potential role in host-bacillus interactions or immune evasion. There are no genes unique to M. bovis, implying that differential gene expression may be the key to the host tropisms of human and bovine bacilli. The genome sequence offers major insight into the evolution, host preference, and pathobiology of M. bovis. M. bovis is the causative agent of tuberculosis in a range of animal species and humans, with significant economic losses to agriculture. It is also the progenitor of the BCG vaccine strain. The genome sequence of M. bovis AF2122/97 is 4,345,492 bp in length, arranged in a single circular chromosome with an average G + C content of 65.63%. The genome contains 3,952 genes, including a prophage and 42 IS elements. The genome is >99.95% identical to that of M. tuberculosis at the nucleotide level, showing colinearity and no evidence of extensive translocations, duplications or inversions. The genome sequence reveals that M. bovis has undergone significant deletions, with only one locus, TbD1, unique to it. Comparison with M. tuberculosis shows 2,437 SNPs between M. bovis and M. tuberculosis H37Rv, and 2,423 SNPs with M. tuberculosis CDC1551. These SNPs are responsible for distinctive characteristics of the bovine bacillus, such as resistance to pyrazinamide. The genome sequence also shows variation in genes encoding cell wall and secreted proteins, which may play a role in host interactions or immune evasion. The genome sequence of M. bovis provides insights into the evolution, host preference, and pathobiology of the organism. It also highlights the importance of gene expression and cell envelope components in the adaptation of M. bovis to different hosts. The genome sequence has implications for the development of new control strategies for bovine tuberculosis, as well as for the understanding of the pathogenesis of tuberculosis in humans. The sequence also reveals that M. bovis has undergone significant genome downsizing, with many genes either deleted or inactivated, suggesting that the loss of genes may be a key factor in the adaptation of the organism to different hosts. The genome sequence of M. bovis is a valuable resource for understanding the biology of