Comparing UT205 draft genome against H37Rv, CDC1551, F11 and KZN genomes, we also identify UT205 large indels (more than 30 bases) that affected either intergenic or coding regions (Table 2). To compare the differences within the protein coding, we undertook a complete orthologous genes comparison against the H37Rv predicted coding sequences using a global alignment

protocol of the fasta36 package, GGSEARCH. All predicted 3701 CDS AZD2281 mw of UT205 were translated into proteins and compared with the predicted 3998 proteome of H37Rv. For this analysis, all the PPE,vPE-PGRS and genes with sequence ambiguities or gaps (Ns) were excluded. Global protein identity analysis showed that 3271 (88.38%) of the UT205 display 100% identity with H37Rv. The remaining 430 (11.62%) proteins showed changes in at least one amino acid. From those, 388 proteins (10.48%) have an identity between 99.99% and 90%, 15 between 89.99% and 60% (0.41%) identity and 27 < 60% (0.73%) identity. Changes in protein-coding genes were owing to substitutions that introduced premature Etoposide cell line stop codons, or indels that changed the translation frame and generated either truncated or longer proteins owing to the modification of the original stop triplet. Compared to H37Rv, insertions that

modify CDS sequences ranged from 1 to 531 bases (Table 3). The most affected genes, with < 90% identity are listed in Table 3. A detailed analysis of the regulon DosR in the UT205 strain was carried out. Of the 48 genes that compose this regulon, eight genes present modifications. These modifications involve complete gene deletions (such as in the case of Rv1996), clonidine indels or SNPs in other seven genes (Table 4). The most interesting case involves the 3649 bp deletion, affecting the Rv1996/Rv1997 operon. This deletion eliminates Rv1996 genes and also the intergenic region upstream up to Rv1992c, where the DosR regulated promoter of this operon should be. This implies that both, Rv1996 and Rv1997, should not be expressed owing to a complete deletion and the

loss of the promoter region, respectively (Fig. 3). Pathogen adaptations to its human population hosts have been described in M. tuberculosis (Gagneux et al., 2006; Gagneux & Small, 2007), indicating that this species is more genetically diverse than originally believed. In-depth genomic analysis of Latin American species of M. tuberculosis has not been published so far, and some specific adaptation to this population should be expected, as observed in other human populations. Whole genome shotgun sequencing analysis of UT205 strain showed several differences with reference strains. IS6110 insertion elements were polymorphic compared to other LAM and no LAM reference strains, with novel insertions sites. Nucleotide large sequence polymorphisms showed insertions and deletions that could be specific for the Colombian strains.