Complete Genome Sequencing of Mycobacterium bovis SP38 and Comparative Genomics of Mycobacterium bovis and M. tuberculosis Strains

causes bovine tuberculosis and is the main organism responsible for zoonotic tuberculosis in humans. We performed the sequencing, assembly and annotation of a Brazilian strain of named SP38, and performed comparative genomics of genomes deposited in GenBank. SP38 has a traditional tuberculous mycobacterium genome of 4,347,648 bp, with 65.5% GC, and 4,216 genes. The majority of CDSs (2,805, 69.3%) have predictive function, while 1,206 (30.07%) are hypothetical. For comparative analysis, 31 , 32 BCG, and 23 genomes available in GenBank were selected. RDs (regions of difference) and Clonal Complexes (CC) were identified . Genome dynamics of bacterial groups were analyzed by gene orthology and polymorphic sites identification. polymorphic sites were used to construct a phylogenetic tree. Our RD analyses resulted in the exclusion of three genomes, mistakenly annotated as virulent . SP38 along with strain 35 represent the first report of CC European 2 in Brazil, whereas two other strains failed to be classified within current CC. Results of orthologous genes analysis suggest a process of genome remodeling through genomic decay and gene duplication. Quantification, pairwise comparisons and distribution analyses of polymorphic sites demonstrate greater genetic variability of when compared to and BCG ( ≤ 0.05), indicating that currently defined lineages are more genetically diverse than CC and animal-adapted MTC ( Complex) species. As expected, polymorphic sites annotation shows that BCG are subjected to different evolutionary pressures when compared to virulent mycobacteria. Lastly, phylogeny indicates that polymorphic sites may be used as markers of lineages in association with CC. Our findings highlight the need to better understand host-pathogen co-evolution in genetically homogeneous and/or diverse host populations, considering the fact that has a broader host range when compared to . Also, the identification of genomes not classified within CC indicates that the diversity of lineages may be larger than previously thought or that current classification should be reviewed.