Genetic Profiling of the Isoprenoid and Sterol Biosynthesis Pathway Genes of Trypanosoma cruzi

Authors
Cosentino, Raúl Oscar; Agüero, Fernan Gonzalo
Publication Year
2014
Language
English
Format
article
Status
Published version
Description
InTrypanosoma cruzithe isoprenoid and sterol biosynthesis pathways are validated targets for chemotherapeuticintervention. In this work we present a study of the genetic diversity observed in genes from these pathways. Using anumber of bioinformatic strategies, we first identified genes that were missing and/or were truncated in theT. cruzigenome. Based on this analysis we obtained the complete sequence of the ortholog of the yeast ERG26 gene and identifieda non-orthologous homolog of the yeast ERG25 gene (sterol methyl oxidase, SMO), and we propose that the orthologs ofERG25 have been lost in trypanosomes (but not in Leishmanias). Next, starting from a set of 16T. cruzistrains representativeof all extant evolutionary lineages, we amplified and sequenced,24 Kbp from 22 genes, identifying a total of 975 SNPs orfixed differences, of which 28% represent non-synonymous changes. We observed genes with a density of substitutionsranging from those close to the average (,2.5/100 bp) to some showing a high number of changes (11.4/100 bp, for theputative lathosterol oxidase gene). All the genes of the pathway are under apparent purifying selection, but genes codingfor the sterol C14-demethylase, the HMG-CoA synthase, and the HMG-CoA reductase have the lowest density of missenseSNPs in the panel. Other genes (TcPMK, TcSMO-like) have a relatively high density of non-synonymous SNPs (2.5 and 1.9every 100 bp, respectively). However, none of the non-synonymous changes identified affect a catalytic or ligand bindingsite residue. A comparative analysis of the corresponding genes from African trypanosomes andLeishmaniashows similarlevels of apparent selection for each gene. This information will be essential for future drug development studies focused onthis pathway.
Fil: Cosentino, Raúl Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Agüero, Fernan Gonzalo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina
Subject
trypanosoma cruzi
sterol biosynthesis pathway
isoprenoid biosynthesis pathway
SNPs
Otras Ciencias Biológicas
Ciencias Biológicas
CIENCIAS NATURALES Y EXACTAS
Access level
Open access
License
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repository
CONICET Digital (CONICET)
Institution
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identifier
oai:ri.conicet.gov.ar:11336/32326