PT  - JOURNAL ARTICLE
AU  - Jue Wang
AU  - Julius Palme
AU  - Kayla B. Lee
AU  - Michael Springer
TI  - Natural Genetic Variation Can Independently Tune the Induced Fraction and Induction Level of a Bimodal Signaling Response
AID  - 10.1101/131938
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 131938
4099  - http://biorxiv.org/content/early/2017/04/28/131938.short
4100  - http://biorxiv.org/content/early/2017/04/28/131938.full
AB  - Bimodal gene expression by genetically identical cells is a pervasive feature of signaling networks, but the mechanisms modulating bimodality are poorly understood. We found that natural yeast strains induce the galactose-utilization (GAL) pathway with a variety of bimodal phenotypes in mixtures of glucose and galactose. The phenotypic variation can be described in terms of two uncorrelated features representing the fraction of cells that are induced and the expression level of the induced subpopulation. We mapped genomic loci underlying these two traits using bulk-segregant analysis, identified causal genes in 3 loci, and phenotyped allele-replacement strains containing all allelic combinations of these genes. One gene affected only the induced fraction of the GAL response, another affected only the level of induction, and a third gene affected both traits. Additionally, the genetic effect on induced fraction could be phenocopied by varying the growth conditions prior to galactose induction. Our results show that different quantitative features of a bimodal signaling response can be tuned independently by genetic and environmental perturbations, and that this tuning can change the response from unimodal to bimodal. This modularity may help cells adapt to complex natural environments on physiological as well as evolutionary timescales.