Navegando por Palavras-chave "Intragenic recombination"

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    ABCG-like transporter of Trypanosoma cruzi involved in benznidazole resistance: Gene polymorphisms disclose inter-strain intragenic recombination in hybrid isolates
    (Elsevier B.V., 2015-04-01) Franco, Jaques; Ferreira, Renata C. [UNIFESP]; Ienne, Susan; Zingales, Bianca; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP)
    Benznidazole (BZ) is one of the two drugs for Chagas disease treatment. in a previous study we showed that the Trypanosoma cruzi ABCG-like transporter gene, named TcABCG1, is over-expressed in parasite strains naturally resistant to BZ and that the gene of TcI BZ-resistant strains exhibited several single nucleotide polymorphisms (SNPs) as compared to the gene of CL Brener BZ-susceptible strain. Here we report the sequence of TcABCG1 gene of fourteen Trypanosoma cruzi strains, with diverse degrees of BZ sensitivity and belonging to different discrete typing units (DTUs) and Tcbat group. Although DTU-specific SNPs and amino acid changes were identified, no direct correlation with BZ-resistance phenotype was found. Thus, it is plausible that the transporter abundance is a determinant factor for drug resistance, as pointed out above. Sequence data were used for Bayesian phylogenies and network genealogy analysis. the network showed a high degree of reticulation suggesting genetic exchange between the parasites. TcI and TcII clades were clearly separated. Tcbat sequences were close to TcI. A fourth clade clustered TcABCG1 haplotypes of TcV, TcVI and TcIII strains, with closer proximity to TcI. Analysis of the recombination patterns indicated that hybrid strains contain haplotypes that are mosaics most likely derived by intragenic recombination of parental sequences. the data confirm that TcII and Mill as the parentals of TcV and TcVI DTUs. Since genetic fingerprint of TcI was found in TcIII, we sustain the previously proposed Two Hybridization model for the origin of hybrid strains. Among the twenty best BLASTP hits in databases, orthologues of TcABCG1 transporter were found in Leishmania spp. and African trypanosomes, though their function remains undescribed. (C) 2015 Elsevier B.V. All rights reserved.
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    Phylogenetic evidence based on Trypanosoma cruzi nuclear gene sequences and information entropy suggest that inter-strain intragenic recombination is a basic mechanism underlying the allele diversity of hybrid strains
    (Elsevier B.V., 2012-07-01) Ferreira, Renata Carmona [UNIFESP]; Briones, Marcelo Ribeiro da Silva [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    The diversity of Trypanosoma cruzi is categorized into six discrete typing units (DTUs) T. cruzi I to VI. Several studies indicate that T. cruzi I and II are ancestors of T. cruzi which are considered products of independent hybridization events. the individual haplotypes or alleles of these hybrids cluster in three groups, either closer to T. cruzi I or T. cruzi II or forming a midpoint clade between T. cruzi I and II in network phylogenies. To understand the origins of these different sets of haplotypes and test the hypothesis of a direct correlation between high entropy and positive selection, we analyzed four nuclear protein coding genes. We show that hybrid strains contain haplotypes that are mosaics probably originated by intragenic recombination. Accordingly, in phylogenies, the hybrid haplotypes are closer to one or both parentals (T. cruzi I and II) depending on the proportion of parental sequences composing the mosaics. in addition, Shannon entropy, used to measure sequence diversity, is highly correlated with positive selection in the four genes here analyzed. Our data on recombination patterns also support the hypothesis of two hybridization events in the hybrid structures of T. cruzi Data presented and discussed here are consistent with a scenario where TcI and TcII are phylogenetically divergent forming a hybrid zone in between (T. cruzi III-VI). We predict that because of the quasi-random nature of T. cruzi I and II hybridization more DTUs, with different haplotype combinations, will be discovered in the hybrid zone. (C) 2012 Elsevier B.V. All rights reserved.