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

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 mi...

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Detalles Bibliográficos
Autores: Cosentino, Raúl Oscar, Agüero, Fernan Gonzalo
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2014
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/32326
Acceso en línea:http://hdl.handle.net/11336/32326
Access Level:acceso abierto
Palabra clave:trypanosoma cruzi
sterol biosynthesis pathway
isoprenoid biosynthesis pathway
SNPs
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
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spelling Genetic Profiling of the Isoprenoid and Sterol Biosynthesis Pathway Genes of Trypanosoma cruziCosentino, Raúl OscarAgüero, Fernan Gonzalotrypanosoma cruzisterol biosynthesis pathwayisoprenoid biosynthesis pathwaySNPshttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1InTrypanosoma 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; ArgentinaFil: 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; ArgentinaPublic Library of Science2014-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/32326Agüero, Fernan Gonzalo; Cosentino, Raúl Oscar; Genetic Profiling of the Isoprenoid and Sterol Biosynthesis Pathway Genes of Trypanosoma cruzi; Public Library of Science; Plos One; 9; 5; 5-2014; 1-161932-6203CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0096762info:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0096762info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2024-05-08T13:50:42Zoai:ri.conicet.gov.ar:11336/32326instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982024-05-08 13:50:43.151CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Genetic Profiling of the Isoprenoid and Sterol Biosynthesis Pathway Genes of Trypanosoma cruzi
title Genetic Profiling of the Isoprenoid and Sterol Biosynthesis Pathway Genes of Trypanosoma cruzi
spellingShingle Genetic Profiling of the Isoprenoid and Sterol Biosynthesis Pathway Genes of Trypanosoma cruzi
Cosentino, Raúl Oscar
trypanosoma cruzi
sterol biosynthesis pathway
isoprenoid biosynthesis pathway
SNPs
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
title_short Genetic Profiling of the Isoprenoid and Sterol Biosynthesis Pathway Genes of Trypanosoma cruzi
title_full Genetic Profiling of the Isoprenoid and Sterol Biosynthesis Pathway Genes of Trypanosoma cruzi
title_fullStr Genetic Profiling of the Isoprenoid and Sterol Biosynthesis Pathway Genes of Trypanosoma cruzi
title_full_unstemmed Genetic Profiling of the Isoprenoid and Sterol Biosynthesis Pathway Genes of Trypanosoma cruzi
title_sort Genetic Profiling of the Isoprenoid and Sterol Biosynthesis Pathway Genes of Trypanosoma cruzi
dc.creator.none.fl_str_mv Cosentino, Raúl Oscar
Agüero, Fernan Gonzalo
author Cosentino, Raúl Oscar
author_facet Cosentino, Raúl Oscar
Agüero, Fernan Gonzalo
author_role author
author2 Agüero, Fernan Gonzalo
author2_role author
dc.subject.none.fl_str_mv trypanosoma cruzi
sterol biosynthesis pathway
isoprenoid biosynthesis pathway
SNPs
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
topic trypanosoma cruzi
sterol biosynthesis pathway
isoprenoid biosynthesis pathway
SNPs
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
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.
publishDate 2014
dc.date.none.fl_str_mv 2014-05
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/32326
Agüero, Fernan Gonzalo; Cosentino, Raúl Oscar; Genetic Profiling of the Isoprenoid and Sterol Biosynthesis Pathway Genes of Trypanosoma cruzi; Public Library of Science; Plos One; 9; 5; 5-2014; 1-16
1932-6203
CONICET Digital
CONICET
url http://hdl.handle.net/11336/32326
identifier_str_mv Agüero, Fernan Gonzalo; Cosentino, Raúl Oscar; Genetic Profiling of the Isoprenoid and Sterol Biosynthesis Pathway Genes of Trypanosoma cruzi; Public Library of Science; Plos One; 9; 5; 5-2014; 1-16
1932-6203
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0096762
info:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0096762
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 15,812429

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