Genome adaptation to chemical stress: clues from comparative transcriptomics in Saccharomyces cerevisiae and Candida glabrata. Genome Biol 9:R164

Equipe de Bioinformatique Génomique et Moléculaire, INSERM UMR S726, Université Paris 7, INTS, 6 rue Alexandre Cabanel, 75015 Paris, France.
Genome biology (Impact Factor: 10.81). 12/2008; 9(11):R164. DOI: 10.1186/gb-2008-9-11-r164
Source: PubMed


Recent technical and methodological advances have placed microbial models at the forefront of evolutionary and environmental genomics. To better understand the logic of genetic network evolution, we combined comparative transcriptomics, a differential clustering algorithm and promoter analyses in a study of the evolution of transcriptional networks responding to an antifungal agent in two yeast species: the free-living model organism Saccharomyces cerevisiae and the human pathogen Candida glabrata.
We found that although the gene expression patterns characterizing the response to drugs were remarkably conserved between the two species, part of the underlying regulatory networks differed. In particular, the roles of the oxidative stress response transcription factors ScYap1p (in S. cerevisiae) and Cgap1p (in C. glabrata) had diverged. The sets of genes whose benomyl response depends on these factors are significantly different. Also, the DNA motifs targeted by ScYap1p and Cgap1p are differently represented in the promoters of these genes, suggesting that the DNA binding properties of the two proteins are slightly different. Experimental assays of ScYap1p and Cgap1p activities in vivo were in accordance with this last observation.
Based on these results and recently published data, we suggest that the robustness of environmental stress responses among related species contrasts with the rapid evolution of regulatory sequences, and depends on both the coevolution of transcription factor binding properties and the versatility of regulatory associations within transcriptional networks.

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    • "In contrast to S. cerevisiae (DeRisi et al., 2000), however, no remarkable overexpression of CgPDR16 has been observed in transcriptome analyses using strains either containing gain-of-function CgPDR1 alleles (Vermitsky et al., 2006; Tsai et al., 2010; Caudle et al., 2011; Ferrari et al., 2011) or exposed to drugs (Lelandais et al., 2008). "
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    ABSTRACT: The PDR16 gene encodes the homologue of Sec14p participating in protein secretion, regulation of lipid synthesis and turnover in vivo, and acting as a phosphatidylinositol transfer protein in vitro. This gene is also involved in regulation of multidrug resistance in Saccharomyces cerevisiae and pathogenic yeasts. Here, we report the results of functional analysis of the CgPDR16 gene whose mutation has been previously shown to enhance the fluconazole sensitivity in Candida glabrata mutant cells. We have cloned the CgPDR16 gene which was able to complement the pdr16Δ mutation in both C. glabrata and S. cerevisiae. Along with fluconazole, the pdr16Δ mutation resulted in the increased susceptibility of mutant cells to several azole antifungals without changes in the sensitivity to polyene antibiotics, cycloheximide, NQO, 5-fluorocytosine and the oxidants inducing intracellular formation of reactive oxygen species. The susceptibility of the pdr16Δ mutant strain to itraconazole and 5-fluorocytosine was enhanced by CTBT (7-chlorotetrazolo[5,1-c]benzo[1,2,4]triazine) inducing oxidative stress. The pdr16Δ mutation increased the accumulation of rhodamine 6G in mutant cells, decreased the level of itraconazole resistance caused by gain-of-function mutations in the CgPDR1 gene, and reduced the cell surface hydrophobicity and biofilm production. These results point to the pleiotropic phenotype of the pdr16Δ mutant and support the role of the CgPDR16 gene in the control of drug susceptibility and virulence in the pathogenic C. glabrata. This article is protected by copyright. All rights reserved.
    Full-text · Article · Aug 2013 · Yeast
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    • "Due to the S. cerevisiae arrays used, they were unable to examine more divergent species. In order to broaden these studies to more divergent yeasts, species-specific arrays must be used, as has been done, for example, for Candida glabrata[27]. Most importantly, due to the limited condition space of just a small number of treatments in these studies, conclusions about evolution of gene function and regulation have been difficult to generalize. "
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    ABSTRACT: Background Comparative genomics brings insight into sequence evolution, but even more may be learned by coupling sequence analyses with experimental tests of gene function and regulation. However, the reliability of such comparisons is often limited by biased sampling of expression conditions and incomplete knowledge of gene functions across species. To address these challenges, we previously systematically generated expression profiles in Saccharomyces bayanus to maximize functional coverage as compared to an existing Saccharomyces cerevisiae data repository. Results In this paper, we take advantage of these two data repositories to compare patterns of ortholog expression in a wide variety of conditions. First, we developed a scalable metric for expression divergence that enabled us to detect a significant correlation between sequence and expression conservation on the global level, which previous smaller-scale expression studies failed to detect. Despite this global conservation trend, between-species gene expression neighborhoods were less well-conserved than within-species comparisons across different environmental perturbations, and approximately 4% of orthologs exhibited a significant change in co-expression partners. Furthermore, our analysis of matched perturbations collected in both species (such as diauxic shift and cell cycle synchrony) demonstrated that approximately a quarter of orthologs exhibit condition-specific expression pattern differences. Conclusions Taken together, these analyses provide a global view of gene expression patterns between two species, both in terms of the conditions and timing of a gene's expression as well as co-expression partners. Our results provide testable hypotheses that will direct future experiments to determine how these changes may be specified in the genome.
    Full-text · Article · Jan 2013 · BMC Genomics
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    • "The resulting gene expression profiles are then compared with various information, including orthology links, functional annotations from the gene ontology (GO) and the conservation of known cisregulatory elements in orthologous promoters. To do so, several methodologies have been published, including the direct comparison of gene expression profiles from orthologous genes [12] [13] [14] [15], the quantification of the coexpression conservation of clusters of genes [16] [17] or multispecies fuzzy clustering using orthology links as a constraint to optimize GO enrichment in the final clusters [18]. To our knowledge, the most impressive work of this kind has been performed by the laboratory of Aviv Regev and her collaborators (Dawn Anne Thompson, personal communication ). "
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    ABSTRACT: Gene regulation is a major source of phenotypic diversity between and within species. This aspect of evolution has long been addressed from the sole point of view of the genome sequence. The incredible development of transcriptomics approaches now allows one to actually study the topology and the properties of regulatory networks on an evolutionary perspective. This new discipline is called comparative functional genomics or comparative transcriptomics. This article reviews some of the main advances made in this field, using yeast species, and especially the species sequenced in the frame of the Genolevures program, as a model.
    Full-text · Article · Aug 2011 · Comptes rendus biologies
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