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{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/1343551","sourcedb":"PMC","sourceid":"1343551","source_url":"http://www.ncbi.nlm.nih.gov/pmc/1343551","text":"Divergence of the in vivo-responsive genes in the three species\nTo distinguish diverged genes from those conserved between two compared genomes, we defined an arbitrary standard for significant divergence; i.e. when the % identity or the % length of the match are lower than the genome-wide means by more than two standard deviations (SDs). While a universal standard that applies to all genes equally does not exist, using this standard we tentatively organized the genes into sub-groups of relative divergence (Fig. 3A; a complete list is given in Additional file 4). When only the in vivo expression data was used, 60.5% (178 genes) of the group 1 and 3 genes (in vivo-up-expressed) and 86.5% (365 genes) of the group 2 (down-expressed) genes are conserved between Bm and Bt (Fig. 3B). In contrast, 89.4% (262 genes) of the genes in the groups 1 and 3 and 95.7% (404 genes) of the genes in the group 2 are conserved between Bm and Bp (Fig. 3B; Additional file 5).\nFigure 3 Comparison among B. mallei, B. pseudomallei, and B. thailandensis with a divergence cut-off of two-times of standard deviation from the mean values of identity and length match. Venn diagrams show the numbers of genes common or diverged or unique to each genome. Genes in the diagrams are shown in Additional files 4, 5 and 6. A. Comparisons generated based on the TBLASTN scores with the proteome of one genome to the nucleotide sequences of other genomes. Segments labeled 1, 2, 3, 4 are based on the Bm proteome, while segments 5 and 6 are based on the Bp proteome and segment 7 is based on the Bt proteome. B. Comparisons with in vivo-responsive group 1 and 3 genes and group 2 genes (see Figure 1). The data indicate that Bt also shares a number of the up-expressed genes (178), while there also are many that are diverged significantly or absent (116). The 178 up-expressed genes include a number of genes that may be involved in survival in the host (e.g., TTSS-2 genes, iron uptake genes, anaerobic respiration genes, LPS biosynthesis genes, degradative enzymes, etc.).\nThe 86 up-expressed genes that are conserved in Bm and Bp but not as well in Bt are of special interest because they may contain the genes that contribute to the distinction of Bp and Bm as animal pathogens from non-pathogenic Bt. Genes in this group include those encoding putative detoxification or resistance function for toxins (e.g., BMA1038 putative penicillin amidase and BMA0952 NodT family RND efflux system), secondary metabolite biosynthesis (e.g., BMA1123 peptide synthetase and BMAA1202 polyketide synthase), some TTSS genes (e.g., BMAA1617 putative hrp protein and BMAA1619 hypothetical protein), and cell envelope synthesis genes (e.g., BMAA0751 N-acetylmuramoyl-L-alanine amidase domain protein, BMAA1498 putative O-antigen acetylase, BMAA1986 ADP-heptose-LPS heptosyltransferase II, BMAA1987 glycosyl transferase).\nThere are 30 up-expressed genes that appear to have diverged in Bm even relative to their Bp ortholog. Twenty one of these have frame-shift mutations relative to their counterparts in Bp resulting in rather dramatic changes in the proteins that they code for, while eight have only subtle in-frame mutations and one is completely absent in Bp (Additional file 6). At least some of these possibly code for functional Bm-unique proteins. Seven of the eight genes with in-frame mutations do not have assigned predicted functions, but one (BMA0605) is weakly related to hemerythrin-coding gene in Ralstonia solanacearm, the product of which is involved in oxygen transfer and/or storage. One of the eight (BMAA1526) is related to the bapA gene in Borrelia burgdorferi. The bapA gene present in many B. burgdorferi isolates is linked to the virulence-involved erp locus and was shown to be co-expressed with the locus [19]. While the exact function is unknown, it is suspected that bapA may also perform an important function for B. furgdorferi virulence, based on its genetic pairing with the erp genes and immunological evidence [20]. BMAA0610, which codes for di-haem cytochrome C peroxidase family protein and is only present in Bm, is related to enzymes in Pseudomonas aeruginosa and Neisseria gonorrhoeae that are located in the periplasm where their likely function is to provide protection against toxic peroxides [21,22]. In N. gonorrhoeae, the gene was shown to be induced during oxygen-limiting growth.","divisions":[{"label":"Title","span":{"begin":0,"end":63}},{"label":"Figure caption","span":{"begin":967,"end":1682}}],"tracks":[]}