Variation in the modality of a yeast signaling pathway is mediated by a single regulator

Bimodal gene expression by genetically identical cells is a pervasive feature of signaling networks, and has been suggested to allow organisms to hedge their "bets" in uncertain conditions. In the galactose-utilization (GAL) pathway of Saccharomyces cerevisiae, gene induction is unimodal or bimodal depending on natural genetic variation and pre-induction conditions. Here, we find that this variation in modality arises from regulation of two features of the pathway response: the fraction of cells that show induction, and their level of expression. GAL3, the galactose sensor, controls the fraction of induced cells, and titrating its expression is sufficient to control modality; moreover, all the observed differences in modality between different pre-induction conditions and amongst natural isolates can be explained by changes in GAL3's regulation and activity. The ability to switch modality by tuning the activity of a single protein may allow rapid adaptation of bet hedging to maximize fitness in complex environments.

A new genome-wide method to identify genes with bimodal gene expression

A new method is presented to detect bimodality in gene expression data using the Gaussian Mixture Models to cluster samples in each mode. We have used the method to search for bimodal genes in data from 25 tumor types available from The Cancer Genome Atlas. The method identified 554 genes with bimodal gene expression, of which 46 were identified in more than one cancer type. To further illustrate the impact of the method, we show that 96 out of the 554 genes with bimodal expression patterns presented different prognosis when patients belonging to the two expression peaks are compared. The software to execute the method and the corresponding documentation are available at https://github.com/LabBiosystemUFRN/Bimodality_Genes.

Variation in the modality of a yeast signaling pathway is mediated by a single regulator

Bimodal gene expression by genetically identical cells is a pervasive feature of signaling networks. In the galactose-utilization (GAL) pathway ofSaccharomyces cerevisiae, induction can be unimodal or bimodal depending on natural genetic variation and pre-induction conditions. Here, we find that this variation of modality is regulated by an interplay between two features of the pathway response, the fraction of cells that are in the induced subpopulation and their expression level. Combined, the variations in these features are sufficient to explain the observed effects of natural variation and pre-induction conditions on the modality of induction in both mechanistic and phenomenological models. Both natural variation and pre-induction conditions act by modulating the expression and function of the galactose sensorGAL3. The ability to alter modality may allow organisms to adapt their level of “bet hedging” to the conditions they experience, and thus help optimize fitness in complex, fluctuating natural environments.