The complete genome sequence of Mycobacterium bovis

Abstract

Mycobacterium bovis is the causative agent of tuberculosis in a range of animal species and man, with worldwide annual losses to agriculture of $3 billion. The human burden of tuberculosis caused by the bovine tubercle bacillus is still largely unknown. M. bovis was also the progenitor for the M. bovis bacillus Calmette-Guérin vaccine strain, the most widely used human vaccine. Here we describe the 4,345,492-bp genome sequence of M. bovis AF2122/97 and its comparison with the genomes of Mycobacterium tuberculosis and Mycobacterium leprae. Strikingly, the genome sequence of M. bovis is >99.95% identical to that of M. tuberculosis, but deletion of genetic information has led to a reduced genome size. Comparison with M. leprae reveals a number of 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. Furthermore, 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 therefore offers major insight on the evolution, host preference, and pathobiology of M. bovis.

Fig. 1.

Circular representation of the M. bovis genome. The scale is shown in megabases by the outer black circle. Moving in from the outside, the next two circles show forward and reverse strand CDS, respectively, with colors representing the functional classification. Comparisons with the M. tuberculosis H37Rv sequence are then shown, with transitions (yellow) and transversions (green), then insertions (red, 1 bp; black >1 bp) and deletions (dark blue, 1 bp; light blue >1 bp); sequence replacements by novel regions in M. bovis are then shown (purple). IS elements and phage (cyan) are displayed in the following circle, with G+C content and then finally GC bias (G-C)/(G+C) shown by using a 20-kb window.

Fig. 2.

Tripartite comparison of 2,504 CDS of M. bovis, M. tuberculosis H37Rv, and M. tuberculosis CDC1551. The colors represent the M. bovis–M. tuberculosis H37Rv comparison (red), M. bovis–M. tuberculosis CDC1551 (yellow), and M. tuberculosis H37Rv–M. tuberculosis CDC1551 (blue). The y axis shows numbers of CDS, with the x axis displaying the numbers of SNPs (both synonymous and nonsynonymous).

Fig. 3.

Schematic of the major differences between M. bovis AF2122/97 and M. tuberculosis H37Rv. The blue and red lines represent the cell wall, with blue showing M. tuberculosis and red showing M. bovis. Surface-exposed and transport molecules particular to each bacillus are shown embedded in the wall. Because the large number of differences in the PE-PGRS and PPE are beyond the scope of this diagram, they are merely represented by surface-exposed molecules. Differentially secreted proteins (orange arrows) are shown in each half. The interior of the diagram shows the key steps in carbohydrate metabolism, with the red crosses showing where lesions occur in M. bovis. Proteins that interact with DNA which are inactivated in M. bovis are shown in blue. PGL, phenolic glycolipid; G3P, glycerol 3-phosphate; DHAP, dihydroxyacetone phosphate; PEP, phosphoenolpyruvate; Ald, alanine dehydrogenase.