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Evidence for positive selection in putative virulence factors within the Paracoccidioides brasiliensis species complex.

Matute DR, Quesada-Ocampo LM, Rauscher JT, McEwen JG - PLoS Negl Trop Dis (2008)

Bottom Line: Here, we present evidence indicating that several replacement mutations in gp43 are under positive balancing selection.The other three genes (fks, cdc42 and p27) show very little variation among the P. brasiliensis lineages and appear to be under positive directional selection.We present our results within an evolutionary framework that may be applicable for studying adaptation and pathogenesis in P. brasiliensis and other pathogenic fungi.

View Article: PubMed Central - PubMed

Affiliation: Department of Ecology and Evolution, University of Chicago, Chicago, Illinois, USA. danielricardomatute@gmail.com

ABSTRACT
Paracoccidioides brasiliensis is a dimorphic fungus that is the causative agent of paracoccidioidomycosis, the most important prevalent systemic mycosis in Latin America. Recently, the existence of three genetically isolated groups in P. brasiliensis was demonstrated, enabling comparative studies of molecular evolution among P. brasiliensis lineages. Thirty-two gene sequences coding for putative virulence factors were analyzed to determine whether they were under positive selection. Our maximum likelihood-based approach yielded evidence for selection in 12 genes that are involved in different cellular processes. An in-depth analysis of four of these genes showed them to be either antigenic or involved in pathogenesis. Here, we present evidence indicating that several replacement mutations in gp43 are under positive balancing selection. The other three genes (fks, cdc42 and p27) show very little variation among the P. brasiliensis lineages and appear to be under positive directional selection. Our results are consistent with the more general observations that selective constraints are variable across the genome, and that even in the genes under positive selection, only a few sites are altered. We present our results within an evolutionary framework that may be applicable for studying adaptation and pathogenesis in P. brasiliensis and other pathogenic fungi.

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Related in: MedlinePlus

Posterior probabilities showed by each site in the exon 2 of the PBGP43 gene belonging to site classes with different selective pressures (of 18.20 [black], 1.58 [gray], and 0.00 [white bars]) under the free-ratio model.The gp43 amino acid sequence is shown to the left. Sites with a posterior probability higher than 95% have a greater than 1 and are indicated by an asterisk (*). The underlined parts correspond to the regions that according to SYFPEITHI prediction are potential epitopes.
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pntd-0000296-g003: Posterior probabilities showed by each site in the exon 2 of the PBGP43 gene belonging to site classes with different selective pressures (of 18.20 [black], 1.58 [gray], and 0.00 [white bars]) under the free-ratio model.The gp43 amino acid sequence is shown to the left. Sites with a posterior probability higher than 95% have a greater than 1 and are indicated by an asterisk (*). The underlined parts correspond to the regions that according to SYFPEITHI prediction are potential epitopes.

Mentions: Models of positive selection (discrete, selection, beta and ω models) that allow for sites with ω greater than 1 fit the gp43 data significantly better than the corresponding neutral models (one-ratio, neutral and beta models) (Table 5). Posterior probabilities, as revealed by the discrete model, indicate that the gp43 codons belong to one of the three classes with different selective pressures, as indicated by the beta and ω model (Figure 3). Using the Bayesian Empirical Bayes (BEB) analysis, 19 sites with a posterior probability greater than 95% of having a greater than 1 value were identified. In order to predict potential antigenic determinants for HLA recognition, we used the program SYPFETHI [44]. As illustrated in Figure 3, seven of the sites under positive selection were located as potential epitopes as predicted with SYFPEITHI.


Evidence for positive selection in putative virulence factors within the Paracoccidioides brasiliensis species complex.

Matute DR, Quesada-Ocampo LM, Rauscher JT, McEwen JG - PLoS Negl Trop Dis (2008)

Posterior probabilities showed by each site in the exon 2 of the PBGP43 gene belonging to site classes with different selective pressures (of 18.20 [black], 1.58 [gray], and 0.00 [white bars]) under the free-ratio model.The gp43 amino acid sequence is shown to the left. Sites with a posterior probability higher than 95% have a greater than 1 and are indicated by an asterisk (*). The underlined parts correspond to the regions that according to SYFPEITHI prediction are potential epitopes.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2553485&req=5

pntd-0000296-g003: Posterior probabilities showed by each site in the exon 2 of the PBGP43 gene belonging to site classes with different selective pressures (of 18.20 [black], 1.58 [gray], and 0.00 [white bars]) under the free-ratio model.The gp43 amino acid sequence is shown to the left. Sites with a posterior probability higher than 95% have a greater than 1 and are indicated by an asterisk (*). The underlined parts correspond to the regions that according to SYFPEITHI prediction are potential epitopes.
Mentions: Models of positive selection (discrete, selection, beta and ω models) that allow for sites with ω greater than 1 fit the gp43 data significantly better than the corresponding neutral models (one-ratio, neutral and beta models) (Table 5). Posterior probabilities, as revealed by the discrete model, indicate that the gp43 codons belong to one of the three classes with different selective pressures, as indicated by the beta and ω model (Figure 3). Using the Bayesian Empirical Bayes (BEB) analysis, 19 sites with a posterior probability greater than 95% of having a greater than 1 value were identified. In order to predict potential antigenic determinants for HLA recognition, we used the program SYPFETHI [44]. As illustrated in Figure 3, seven of the sites under positive selection were located as potential epitopes as predicted with SYFPEITHI.

Bottom Line: Here, we present evidence indicating that several replacement mutations in gp43 are under positive balancing selection.The other three genes (fks, cdc42 and p27) show very little variation among the P. brasiliensis lineages and appear to be under positive directional selection.We present our results within an evolutionary framework that may be applicable for studying adaptation and pathogenesis in P. brasiliensis and other pathogenic fungi.

View Article: PubMed Central - PubMed

Affiliation: Department of Ecology and Evolution, University of Chicago, Chicago, Illinois, USA. danielricardomatute@gmail.com

ABSTRACT
Paracoccidioides brasiliensis is a dimorphic fungus that is the causative agent of paracoccidioidomycosis, the most important prevalent systemic mycosis in Latin America. Recently, the existence of three genetically isolated groups in P. brasiliensis was demonstrated, enabling comparative studies of molecular evolution among P. brasiliensis lineages. Thirty-two gene sequences coding for putative virulence factors were analyzed to determine whether they were under positive selection. Our maximum likelihood-based approach yielded evidence for selection in 12 genes that are involved in different cellular processes. An in-depth analysis of four of these genes showed them to be either antigenic or involved in pathogenesis. Here, we present evidence indicating that several replacement mutations in gp43 are under positive balancing selection. The other three genes (fks, cdc42 and p27) show very little variation among the P. brasiliensis lineages and appear to be under positive directional selection. Our results are consistent with the more general observations that selective constraints are variable across the genome, and that even in the genes under positive selection, only a few sites are altered. We present our results within an evolutionary framework that may be applicable for studying adaptation and pathogenesis in P. brasiliensis and other pathogenic fungi.

Show MeSH
Related in: MedlinePlus