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

 

Autores
Cosentino, Raúl Oscar; Agüero, Fernan Gonzalo
Tipo de recurso
artículo
Estado
Versión publicada
Año de publicación
2014
País
Argentina
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio
CONICET Digital (CONICET)
Descripción
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.
Idioma
inglés
OAI Identifier
oai:ri.conicet.gov.ar:11336/32326
Enlace del recurso
http://hdl.handle.net/11336/32326
Nivel de acceso
Acceso abierto
Materia
trypanosoma cruzi
sterol biosynthesis pathway
isoprenoid biosynthesis pathway
SNPs
Otras Ciencias Biológicas
Ciencias Biológicas
CIENCIAS NATURALES Y EXACTAS