Genetic profiling of the isoprenoid and sterol biosynthesis pathway genes of Trypanosoma cruzi

Autor: Raul O Cosentino, Fernán Agüero
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Protozoan Proteins
lcsh:Medicine
Biochemistry
Genome
Mixed Function Oxygenases
purl.org/becyt/ford/1 [https]
Drug Discovery
Medicine and Health Sciences
lcsh:Science
Leishmania
Protozoans
Genetics
Multidisciplinary
via de biosintesis de isoprenoides
Bioquímica y Biología Molecular
Sterols
Metabolic Pathways
Metabolic Networks and Pathways
CIENCIAS NATURALES Y EXACTAS
SNPs
Research Article
Neglected Tropical Diseases
Trypanosoma
3-Hydroxysteroid Dehydrogenases
Saccharomyces cerevisiae Proteins
Drug Research and Development
Otras Ciencias Biológicas
Trypanosoma cruzi
Molecular Sequence Data
Single-nucleotide polymorphism
Saccharomyces cerevisiae
Biology
Polymorphism
Single Nucleotide
sterol biosynthesis pathway
Ciencias Biológicas
Molecular Biology Techniques
Sequencing Techniques
purl.org/becyt/ford/1.6 [https]
Molecular Biology
Gene
Drug Discovery for Neglected Diseases
Pharmacology
Comparative genomics
Evolutionary Biology
Sequence Homology
Amino Acid
via de biosintesis de esteroles
Terpenes
Gene Expression Profiling
lcsh:R
Organisms
Genetic Variation
Membrane Proteins
Biology and Life Sciences
Computational Biology
diversidad genetica
Molecular Sequence Annotation
Comparative Genomics
Lathosterol oxidase
Tropical Diseases
biology.organism_classification
Parasitic Protozoans
Direct Sequencing
Gene expression profiling
Metabolism
Gene Expression Regulation
Genetic Polymorphism
Parasitology
lcsh:Q
isoprenoid biosynthesis pathway
Genome
Protozoan
Population Genetics
Zdroj: PLoS ONE, Vol 9, Iss 5, p e96762 (2014)
CONICET Digital (CONICET)
Consejo Nacional de Investigaciones Científicas y Técnicas
instacron:CONICET
PLoS ONE
ISSN: 1932-6203
Popis: In Trypanosoma cruzi the isoprenoid and sterol biosynthesis pathways are validated targets for chemotherapeutic intervention. In this work we present a study of the genetic diversity observed in genes from these pathways. Using a number of bioinformatic strategies, we first identified genes that were missing and/or were truncated in the T. cruzi genome. Based on this analysis we obtained the complete sequence of the ortholog of the yeast ERG26 gene and identified a non-orthologous homolog of the yeast ERG25 gene (sterol methyl oxidase, SMO), and we propose that the orthologs of ERG25 have been lost in trypanosomes (but not in Leishmanias). Next, starting from a set of 16 T. cruzi strains representative of all extant evolutionary lineages, we amplified and sequenced ∼24 Kbp from 22 genes, identifying a total of 975 SNPs or fixed differences, of which 28% represent non-synonymous changes. We observed genes with a density of substitutions ranging from those close to the average (∼2.5/100 bp) to some showing a high number of changes (11.4/100 bp, for the putative lathosterol oxidase gene). All the genes of the pathway are under apparent purifying selection, but genes coding for the sterol C14-demethylase, the HMG-CoA synthase, and the HMG-CoA reductase have the lowest density of missense SNPs in the panel. Other genes (TcPMK, TcSMO-like) have a relatively high density of non-synonymous SNPs (2.5 and 1.9 every 100 bp, respectively). However, none of the non-synonymous changes identified affect a catalytic or ligand binding site residue. A comparative analysis of the corresponding genes from African trypanosomes and Leishmania shows similar levels of apparent selection for each gene. This information will be essential for future drug development studies focused on this 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
Databáze: OpenAIRE
Externí odkaz: