Phylogenetic tree of selected ERG3/ERG25 orthologs.

<p>Seleced orthologs from kinetoplastids, plants, vertebrates, invertebrates and fungi were aligned with t_coffee. A phylogenetic reconstruction was calculated using PhyML (LG model, bootstrap resampling with N = 1000). For clarity, highly similar genes/alleles were not included in the final tree. Organism abbreviations are: lbra  =  <i>L. braziliensis</i>; lmex  =  <i>L. mexicana</i>; linf  =  <i>L. infantum</i>; lmaj  =  <i>L. major</i>; tcru  =  <i>T. cruzi</i>; tviv  =  <i>T. vivax</i>; tcon  =  <i>T. congolense</i>; tbru  =  <i>T. brucei</i>; agam  =  <i>Anopheles gambiae</i>; aaeg  =  <i>Aedes aegypti</i>; cpip  =  <i>Culex pipiens</i>; hsap  =  <i>Homo sapiens</i>; calb  =  <i>Candida albicans</i>; scer  =  <i>S. cerevisiae</i>; spom  =  <i>Schizosaccharomyces pombe</i>; atha  =  <i>A. thaliana</i>; drer  =  <i>Danio rerio</i>; trub  =  <i>Takifugu rubripes</i>; tnig  =  <i>Tetraodon nigroviridis</i>.</p

Comparative analysis of the quantity, density and type of SNPs identified in the sterol biosynthesis pathway of <i>Trypanosoma cruzi</i>.

<p>SNP counts marked with * indicate totals that do not result from the sum of synonymous + non-synonymous substitutions, in some cases because of the presence of two substitutions in the same codon, and in other cases, because some SNPs fall in the non-coding region of the gene.</p

The <i>T. cruzi</i> sterol biosynthesis pathway.

<p>The figure shows the metabolic steps leading from farnesyl-diphosphate to ergosterol (in yeast, and in <i>T. cruzi</i> epimastigotes) or to different 24-alkylsterols (in <i>T. cruzi</i> amastigotes <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0096762#pone.0096762-Liendo1" target="_blank">[64]</a>), and the corresponding yeast and <i>T. cruzi</i> enzymes that catalyze these steps. The two methyl groups at C4 are removed in two rounds of successive C4-oxidation, C4-decarboxylation and C3-ketoreduction (<b>*</b>). Gene names used are those in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0096762#pone-0096762-t001" target="_blank">Tables 1</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0096762#pone-0096762-t002" target="_blank">2</a>. Unknown/hypothetical assignments are shown with question marks.</p

Alignment of <i>T. cruzi</i>, <i>T. brucei</i>, <i>M. tuberculosis</i> and human Lanosterol 14-<i>α</i> demethylases, showing the non-synonymous changes identified in this work (red arrows).

<p>Important residues either in Tc14DM or in the CYP51 family are noted <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0096762#pone.0096762-Lepesheva4" target="_blank">[100]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0096762#pone.0096762-Lepesheva5" target="_blank">[101]</a>, as well as residues associated with resistance to azoles in <i>C. albicans</i> and <i>U. necator </i><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0096762#pone.0096762-Kelly1" target="_blank">[56]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0096762#pone.0096762-Dlye1" target="_blank">[57]</a>. PS00086 is the Prosite Cytochrome 450 motif (cysteine heme-iron ligand signature).</p

The <i>T. cruzi</i> isoprenoid biosynthesis pathway.

<p>The figure shows the metabolic steps leading to farnesyl-diphosphate, from acetyl-CoA, and the corresponding yeast and <i>T. cruzi</i> enzymes that catalyze these steps. Gene names used are those in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0096762#pone-0096762-t001" target="_blank">Tables 1</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0096762#pone-0096762-t002" target="_blank">2</a>.</p

Genes in the <i>Trypanosoma cruzi</i> sterol biosynthesis pathway.

<p>The table lists <i>T. cruzi</i> genes mapped to either the corresponding KEGG maps, or the yeast SBPs (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0096762#pone-0096762-t001" target="_blank">Table 1</a>). OrthoMCL identifiers are from the OrthoMCL Database version 4. <i>T. cruzi</i> gene identifiers are those currently available at the TriTrypDB resource. The fifth column shows whether the gene was mapped to the corresponding KEGG metabolic map at the time of this writing. The last column shows the nomenclature used in this work. Some of these gene names were previously used in the literature, and others are used here for the first time, based on the gene names of relevant orthologs. In the case of the TcIDI gene, the two listed alleles are truncated copies of the gene. The full-length gene is deposited in GenBank as AJ866772. While in the case of the TcNSDHL gene, the copy annotated by the genome project is truncated due to genome assembly problems. The full-length gene is deposited in GenBank as JN050853 (this work).</p

Comparative analysis of the genetic diversity present in the sterol biosynthesis pathway of different kinetoplastids.

<p>The table shows the dN/dS (<i>ω</i>) ratio observed in the african trypanosome lineage (Af Tryps) (<i>T. brucei brucei</i>, <i>T. brucei gambiense</i>, <i>T. evansi</i>, <i>T. congolense</i>, <i>T. vivax</i>), in the <i>Leishmania</i> lineage (Leish) (<i>L. major</i>, <i>L. infantum</i>, <i>L. braziliensis</i>, and <i>L. mexicana</i>), and in the <i>T. cruzi</i> lineage (Tcr, sequences from TcI{TcVI DTUs). The values that are above (†) or under (*) a standard deviation from the average of each column are marked.</p