Dataset Information

Glucose Repression Signaling 2009

ABSTRACT: Background In the yeast Saccharomyces cerevisiae, the presence of high levels of glucose leads to an array of down-regulatory effects known as glucose repression. This process is complex due to the presence of feedback loops and crosstalk between different pathways, complicating the use of intuitive approaches to analyze the system. Results We established a logical model of yeast glucose repression, formalized as a hypergraph. The model was constructed based on verified regulatory interactions and it includes 50 gene transcripts, 22 proteins, 5 metabolites and 118 hyperedges. We computed the logical steady states of all nodes in the network in order to simulate wildtype and deletion mutant responses to different sugar availabilities. Evaluation of the model predictive power was achieved by comparing changes in the logical state of gene nodes with transcriptome data. Overall, we observed 71% true predictions, and analyzed sources of errors and discrepancies for the remaining. Conclusion Though the binary nature of logical (Boolean) models entails inherent limitations, our model constitutes a primary tool for storing regulatory knowledge, searching for incoherencies in hypotheses and evaluating the effect of deleting regulatory elements involved in glucose repression.

SUBMITTER: Tomas Helikar

PROVIDER: 3511 | Cell Collective |

REPOSITORIES: Cell Collective

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Publications

Reconstruction and logical modeling of glucose repression signaling pathways in Saccharomyces cerevisiae.

Christensen Tobias S TS Oliveira Ana Paula AP Nielsen Jens J

BMC systems biology 20090114

<h4>Background</h4>In the yeast Saccharomyces cerevisiae, the presence of high levels of glucose leads to an array of down-regulatory effects known as glucose repression. This process is complex due to the presence of feedback loops and crosstalk between different pathways, complicating the use of intuitive approaches to analyze the system.<h4>Results</h4>We established a logical model of yeast glucose repression, formalized as a hypergraph. The model was constructed based on verified regulatory ...[more]

PMID: 19144179

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Project description:The yeast Saccharomyces cerevisiae is a model for biology and is also one of the most important microorganisms for food and drink production. Surprisingly, only a few genes involved in the adaptation to anthropic niches have been described until now. Wine fermentation and flor aging, which are performed by strains from two closely related groups of yeast, are two technologies that have opposite approaches toward oxygen, which results in contrasting lifestyles for yeast: fermentation growth on grape for wine yeast, and biofilm aerobic growth on ethanol and glycerol contained in wine for flor strains. This pair of environments and the associated yeast populations can be a model for studying adaptation to anthropic environments. In this project, we have obtained high-quality genome sequences of 20 yeast strains from 9 flor yeast, 9 wine yeast as well as EC1118 and haploid derivative 59A. Phylogeny and population structure analysis, based on GATK genotyping, enable us to characterize a group of flor yeast that is clearly different from wine yeast. A comparison of the genomes of wine and flor yeasts using various methods (PCA, nucleotidic diversity, McDonald Kreitman test, potentially impacted genes according to SIFT) enabled us to note divergent regions, or genes, with potential non-neutral evolution, and highly variant genes. The results of these genomic comparisons are echoed by the comparison of a wine and a flor yeast transcriptome. These methods, as expected, highlight key genes that are involved in FLO11 regulation as well as in biofilm growth, but they also revealed the presence of many allelic variations in genes that are involved in the sensing and regulation of osmotic pressure (such as SLN1, HKR1, SSK22, AQY2) and specific metabolic traits, such as the fructophily of flor yeast, which carry a fructophile allele of HXT3. More remarkable is the accumulation of mutations in multiple genes, which creates a pattern of convergent mutations in regulatory networks, as seen in FLO11 regulation or the HOG MAP kinase pathway. The rewiring of these regulatory networks is clearly one of the hallmarks of domestication for the flor yeast genome. Data presented here correspond to the comparison of Flor yeast P3-D5 and wine yeast K1-280-2B transcriptomes under conditions potentially enabling the production of a biofilm.

Dataset Information

Glucose Repression Signaling 2009

Publications

Reconstruction and logical modeling of glucose repression signaling pathways in Saccharomyces cerevisiae.

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