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Repertoire, genealogy and genomic organization of cruzipain and homologous genes in Trypanosoma cruzi, T. cruzi-like and other trypanosome species.

Lima L, Ortiz PA, da Silva FM, Alves JM, Serrano MG, Cortez AP, Alfieri SC, Buck GA, Teixeira MM - PLoS ONE (2012)

Bottom Line: In this study, we compared 80 sequences of genes encoding cruzipain from 25 T. cruzi isolates representative of all discrete typing units (DTUs TcI-TcVI) and the new genotype Tcbat and 10 sequences of homologous genes from other species.Relatively homogeneous sequences are found within and among isolates of the same DTU except TcV and TcVI, which displayed sequences unique or identical to those of TcII and TcIII, supporting their origin from the hybridization between these two DTUs.Our findings corroborate cruzipain as valuable target for drugs, vaccine, diagnostic and genotyping approaches.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Parasitologia, ICB, Universidade de São Paulo, São Paulo, São Paulo, Brasil.

ABSTRACT
Trypanosoma cruzi, the agent of Chagas disease, is a complex of genetically diverse isolates highly phylogenetically related to T. cruzi-like species, Trypanosoma cruzi marinkellei and Trypanosoma dionisii, all sharing morphology of blood and culture forms and development within cells. However, they differ in hosts, vectors and pathogenicity: T. cruzi is a human pathogen infective to virtually all mammals whilst the other two species are non-pathogenic and bat restricted. Previous studies suggest that variations in expression levels and genetic diversity of cruzipain, the major isoform of cathepsin L-like (CATL) enzymes of T. cruzi, correlate with levels of cellular invasion, differentiation, virulence and pathogenicity of distinct strains. In this study, we compared 80 sequences of genes encoding cruzipain from 25 T. cruzi isolates representative of all discrete typing units (DTUs TcI-TcVI) and the new genotype Tcbat and 10 sequences of homologous genes from other species. The catalytic domain repertoires diverged according to DTUs and trypanosome species. Relatively homogeneous sequences are found within and among isolates of the same DTU except TcV and TcVI, which displayed sequences unique or identical to those of TcII and TcIII, supporting their origin from the hybridization between these two DTUs. In network genealogies, sequences from T. cruzi clustered tightly together and closer to T. c. marinkellei than to T. dionisii and largely differed from homologues of T. rangeli and T. b. brucei. Here, analysis of isolates representative of the overall biological and genetic diversity of T. cruzi and closest T. cruzi-like species evidenced DTU- and species-specific polymorphisms corroborating phylogenetic relationships inferred with other genes. Comparison of both phylogenetically close and distant trypanosomes is valuable to understand host-parasite interactions, virulence and pathogenicity. Our findings corroborate cruzipain as valuable target for drugs, vaccine, diagnostic and genotyping approaches.

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Synteny of a locus containing cruzipain genes in T. cruzi, T. dionisii and T. b. brucei.Segments from the chromosome 6 of T. cruzi CL Brener non-Esmeraldo-like and Esmeraldo-like haplotypes, corresponding to TcIII and TcII, respectively, showing 3 to 4 cruzipain gene copies (entire or partial) flanked by orthologous genes marked with different colors according to the legend. Data from the draft assembly of T. cruzi G, M6241 cl6 and T. dionisii allowed to place one, three or two cruzipain gene copies, respectively, within the same syntenic region (figure do not reflect their actual position on chromosomes). Syntenic region from the chromosome 6 of T. b. brucei comprising 11 copies in tandem of brucipain genes was included in the alignment. The shades of vertical gray bars indicate the variable degrees of divergence between sequences according to the legend. The accession codes of all contigs/scaffolds and GenBank accession numbers (in bold) are presented below the corresponding sequences.
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pone-0038385-g005: Synteny of a locus containing cruzipain genes in T. cruzi, T. dionisii and T. b. brucei.Segments from the chromosome 6 of T. cruzi CL Brener non-Esmeraldo-like and Esmeraldo-like haplotypes, corresponding to TcIII and TcII, respectively, showing 3 to 4 cruzipain gene copies (entire or partial) flanked by orthologous genes marked with different colors according to the legend. Data from the draft assembly of T. cruzi G, M6241 cl6 and T. dionisii allowed to place one, three or two cruzipain gene copies, respectively, within the same syntenic region (figure do not reflect their actual position on chromosomes). Syntenic region from the chromosome 6 of T. b. brucei comprising 11 copies in tandem of brucipain genes was included in the alignment. The shades of vertical gray bars indicate the variable degrees of divergence between sequences according to the legend. The accession codes of all contigs/scaffolds and GenBank accession numbers (in bold) are presented below the corresponding sequences.

Mentions: Chromosome segments from the genome of T. cruzi CL Brener (TcVI) containing three and four tandem copies of cruzipain in Esmeraldo and non-Esmeraldo haplotypes, respectively, were compared with data from the genome drafts of T. cruzi G (TcI), M6241 cl6 (TcIII) and T. dionisii. Homologous segments of chromosome 6 from T. cruzi CL Brener containing cruzipain repeats were found in the genomes of other T. cruzi strains: one cruzipain gene copy from T. cruzi G (of three copies detected in the genome) and three from M6241 cl6 (6 copies in the genome). In the genomes of these strains, cruzipain and homologous genes were flanked by five orthologous genes thus constituting a syntenic block (Fig. 5). Homologous cruzipain genes arranged in the same order were detected in the genomes of T. dionisii (two out of three copies found in the genome draft) and T. b. brucei (an array of 11 identical copies of brucipain in the chromosome 1) (Fig. 5). This syntenic block was selected for this study considering the positioning of cruzipain gene copies from distinct T. cruzi strains and the synteny shared with T. dionisii, T. b. brucei (Fig. 5) and other trypanosome species as showed with T. vivax and T. congolense genome drafts (data not shown).


Repertoire, genealogy and genomic organization of cruzipain and homologous genes in Trypanosoma cruzi, T. cruzi-like and other trypanosome species.

Lima L, Ortiz PA, da Silva FM, Alves JM, Serrano MG, Cortez AP, Alfieri SC, Buck GA, Teixeira MM - PLoS ONE (2012)

Synteny of a locus containing cruzipain genes in T. cruzi, T. dionisii and T. b. brucei.Segments from the chromosome 6 of T. cruzi CL Brener non-Esmeraldo-like and Esmeraldo-like haplotypes, corresponding to TcIII and TcII, respectively, showing 3 to 4 cruzipain gene copies (entire or partial) flanked by orthologous genes marked with different colors according to the legend. Data from the draft assembly of T. cruzi G, M6241 cl6 and T. dionisii allowed to place one, three or two cruzipain gene copies, respectively, within the same syntenic region (figure do not reflect their actual position on chromosomes). Syntenic region from the chromosome 6 of T. b. brucei comprising 11 copies in tandem of brucipain genes was included in the alignment. The shades of vertical gray bars indicate the variable degrees of divergence between sequences according to the legend. The accession codes of all contigs/scaffolds and GenBank accession numbers (in bold) are presented below the corresponding sequences.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3369871&req=5

pone-0038385-g005: Synteny of a locus containing cruzipain genes in T. cruzi, T. dionisii and T. b. brucei.Segments from the chromosome 6 of T. cruzi CL Brener non-Esmeraldo-like and Esmeraldo-like haplotypes, corresponding to TcIII and TcII, respectively, showing 3 to 4 cruzipain gene copies (entire or partial) flanked by orthologous genes marked with different colors according to the legend. Data from the draft assembly of T. cruzi G, M6241 cl6 and T. dionisii allowed to place one, three or two cruzipain gene copies, respectively, within the same syntenic region (figure do not reflect their actual position on chromosomes). Syntenic region from the chromosome 6 of T. b. brucei comprising 11 copies in tandem of brucipain genes was included in the alignment. The shades of vertical gray bars indicate the variable degrees of divergence between sequences according to the legend. The accession codes of all contigs/scaffolds and GenBank accession numbers (in bold) are presented below the corresponding sequences.
Mentions: Chromosome segments from the genome of T. cruzi CL Brener (TcVI) containing three and four tandem copies of cruzipain in Esmeraldo and non-Esmeraldo haplotypes, respectively, were compared with data from the genome drafts of T. cruzi G (TcI), M6241 cl6 (TcIII) and T. dionisii. Homologous segments of chromosome 6 from T. cruzi CL Brener containing cruzipain repeats were found in the genomes of other T. cruzi strains: one cruzipain gene copy from T. cruzi G (of three copies detected in the genome) and three from M6241 cl6 (6 copies in the genome). In the genomes of these strains, cruzipain and homologous genes were flanked by five orthologous genes thus constituting a syntenic block (Fig. 5). Homologous cruzipain genes arranged in the same order were detected in the genomes of T. dionisii (two out of three copies found in the genome draft) and T. b. brucei (an array of 11 identical copies of brucipain in the chromosome 1) (Fig. 5). This syntenic block was selected for this study considering the positioning of cruzipain gene copies from distinct T. cruzi strains and the synteny shared with T. dionisii, T. b. brucei (Fig. 5) and other trypanosome species as showed with T. vivax and T. congolense genome drafts (data not shown).

Bottom Line: In this study, we compared 80 sequences of genes encoding cruzipain from 25 T. cruzi isolates representative of all discrete typing units (DTUs TcI-TcVI) and the new genotype Tcbat and 10 sequences of homologous genes from other species.Relatively homogeneous sequences are found within and among isolates of the same DTU except TcV and TcVI, which displayed sequences unique or identical to those of TcII and TcIII, supporting their origin from the hybridization between these two DTUs.Our findings corroborate cruzipain as valuable target for drugs, vaccine, diagnostic and genotyping approaches.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Parasitologia, ICB, Universidade de São Paulo, São Paulo, São Paulo, Brasil.

ABSTRACT
Trypanosoma cruzi, the agent of Chagas disease, is a complex of genetically diverse isolates highly phylogenetically related to T. cruzi-like species, Trypanosoma cruzi marinkellei and Trypanosoma dionisii, all sharing morphology of blood and culture forms and development within cells. However, they differ in hosts, vectors and pathogenicity: T. cruzi is a human pathogen infective to virtually all mammals whilst the other two species are non-pathogenic and bat restricted. Previous studies suggest that variations in expression levels and genetic diversity of cruzipain, the major isoform of cathepsin L-like (CATL) enzymes of T. cruzi, correlate with levels of cellular invasion, differentiation, virulence and pathogenicity of distinct strains. In this study, we compared 80 sequences of genes encoding cruzipain from 25 T. cruzi isolates representative of all discrete typing units (DTUs TcI-TcVI) and the new genotype Tcbat and 10 sequences of homologous genes from other species. The catalytic domain repertoires diverged according to DTUs and trypanosome species. Relatively homogeneous sequences are found within and among isolates of the same DTU except TcV and TcVI, which displayed sequences unique or identical to those of TcII and TcIII, supporting their origin from the hybridization between these two DTUs. In network genealogies, sequences from T. cruzi clustered tightly together and closer to T. c. marinkellei than to T. dionisii and largely differed from homologues of T. rangeli and T. b. brucei. Here, analysis of isolates representative of the overall biological and genetic diversity of T. cruzi and closest T. cruzi-like species evidenced DTU- and species-specific polymorphisms corroborating phylogenetic relationships inferred with other genes. Comparison of both phylogenetically close and distant trypanosomes is valuable to understand host-parasite interactions, virulence and pathogenicity. Our findings corroborate cruzipain as valuable target for drugs, vaccine, diagnostic and genotyping approaches.

Show MeSH
Related in: MedlinePlus