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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

Observed nonsynonymous differences per site (dN) and synonymous differences per site (dS) in pairwise comparisons for three different partitions of genes.A. Putative Virulence factors. B. Randomly selected controls. C. Both groups of genes analyzed altogether.
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pntd-0000296-g002: Observed nonsynonymous differences per site (dN) and synonymous differences per site (dS) in pairwise comparisons for three different partitions of genes.A. Putative Virulence factors. B. Randomly selected controls. C. Both groups of genes analyzed altogether.

Mentions: To examine the relative degree of mutational saturation in non-synonymous and synonymous substitutions in our dataset, we plotted the number of non-synonymous nucleotide differences between the two P. brasiliensis groups and the common ancestor against the number of synonymous nucleotide differences for both sets of genes (housekeeping and virulence factors) (Figure 2). Additionally, we fitted a linear model (with functional form dN = A(dS)+B) and a model involving a square term dN = (A(dS)2+BdS+C) to the data by the method of least squares [41]. All the statistical analyses were performed with R.


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)

Observed nonsynonymous differences per site (dN) and synonymous differences per site (dS) in pairwise comparisons for three different partitions of genes.A. Putative Virulence factors. B. Randomly selected controls. C. Both groups of genes analyzed altogether.
© Copyright Policy
Related In: Results  -  Collection

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

pntd-0000296-g002: Observed nonsynonymous differences per site (dN) and synonymous differences per site (dS) in pairwise comparisons for three different partitions of genes.A. Putative Virulence factors. B. Randomly selected controls. C. Both groups of genes analyzed altogether.
Mentions: To examine the relative degree of mutational saturation in non-synonymous and synonymous substitutions in our dataset, we plotted the number of non-synonymous nucleotide differences between the two P. brasiliensis groups and the common ancestor against the number of synonymous nucleotide differences for both sets of genes (housekeeping and virulence factors) (Figure 2). Additionally, we fitted a linear model (with functional form dN = A(dS)+B) and a model involving a square term dN = (A(dS)2+BdS+C) to the data by the method of least squares [41]. All the statistical analyses were performed with R.

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