Figure 1.
Phylogenetic reconstruction of the evolutionary relationships between the members of the pe and ppe protein families.
A. Phylogeny of the ppe protein family. The phylogenetic tree was constructed from the phylogenetic analysis done on the 180 aa N-terminal domains of the ppe proteins. The tree was rooted to the outgroup Rv3873 (ppe68), shown to be the first ppe insertion into the ESAT-6 (esx) gene clusters [8]. Figure reproduced from reference 8 with permission of the authors. B. Phylogeny of the pe protein family. The phylogenetic tree was constructed from the phylogenetic analysis done on the 110 aa N-terminal domains of the pe proteins. The tree was rooted to the outgroup Rv3872 (pe35), shown to be the first pe insertion into the ESAT-6 (esx) gene clusters [8]. Figure reproduced from reference 8 with permission of the authors.
Figure 2.
Sequence variation levels in ppe and pe genes.
A. Calculations of sequence variation in 64 ppe genes. Synonymous variations have been ignored. The Y axis shows the proportion of sequences that show variation predicted to result in amino acid changes. A value of 1 indicates that all analysed sequences were unique. Average number of genomes analysed per gene = 15.2. Genes have been grouped together according to their subfamily [8] by colour and subfamilies are also separated by dotted lines. Each vertical bar is subdivided into micromutations (nsSNP's, frameshifts, small in-frame indels) in dark shading and macromutations (homologous recombination, IS6110 integration, partial and whole gene deletions) in light shading. Ppe38 and ppe50 were not included due to hypervariability at the macromutational level [26], [30] and the difficulty in establishing a consensus sequence. For details of all variations detected see Tables S1 and S2. B. Calculations of sequence variation in 33 pe (excluding pgrs) genes. Synonymous variations have been ignored. Average number of isolates analysed per gene = 16.5. The genes from subfamily V (pgrs subfamily, yellow) are those which are classified as members of this subfamily by their N-terminal amino acid sequences [8] but that do not include the long PGRS C-terminal region. For details of all variations detected see Tables S1 and S3.
Table 1.
Details of 18 whole genome sequence isolates used for in silico comparative gene analysis.
Table 2.
Details of clinical isolates used in this study.
Table 3.
Details of the pe and ppe genes examined by whole gene sequencing.