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1.
Elife ; 112022 11 09.
Article in English | MEDLINE | ID: mdl-36350693

ABSTRACT

Stress defense and cell growth are inversely related in bulk culture analyses; however, these studies miss substantial cell-to-cell heterogeneity, thus obscuring true phenotypic relationships. Here, we devised a microfluidics system to characterize multiple phenotypes in single yeast cells over time before, during, and after salt stress. The system measured cell and colony size, growth rate, and cell-cycle phase along with nuclear trans-localization of two transcription factors: stress-activated Msn2 that regulates defense genes and Dot6 that represses ribosome biogenesis genes during an active stress response. By tracking cells dynamically, we discovered unexpected discordance between Msn2 and Dot6 behavior that revealed subpopulations of cells with distinct growth properties. Surprisingly, post-stress growth recovery was positively corelated with activation of the Dot6 repressor. In contrast, cells lacking Dot6 displayed slower growth acclimation, even though they grow normally in the absence of stress. We show that wild-type cells with a larger Dot6 response display faster production of Msn2-regulated Ctt1 protein, separable from the contribution of Msn2. These results are consistent with the model that transcriptional repression during acute stress in yeast provides a protective response, likely by redirecting translational capacity to induced transcripts.


Subject(s)
Saccharomyces cerevisiae Proteins , Saccharomyces cerevisiae , Saccharomyces cerevisiae/metabolism , Saccharomyces cerevisiae Proteins/genetics , Saccharomyces cerevisiae Proteins/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Acclimatization , Phenotype , Gene Expression Regulation, Fungal , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Repressor Proteins/genetics , Repressor Proteins/metabolism
2.
Mol Biol Evol ; 33(5): 1270-9, 2016 05.
Article in English | MEDLINE | ID: mdl-26782997

ABSTRACT

Qualitative patterns of gene activation and repression are often conserved despite an abundance of quantitative variation in expression levels within and between species. A major challenge to interpreting patterns of expression divergence is knowing which changes in gene expression affect fitness. To characterize the fitness effects of gene expression divergence, we placed orthologous promoters from eight yeast species upstream of malate synthase (MLS1) in Saccharomyces cerevisiae As expected, we found these promoters varied in their expression level under activated and repressed conditions as well as in their dynamic response following loss of glucose repression. Despite these differences, only a single promoter driving near basal levels of expression caused a detectable loss of fitness. We conclude that the MLS1 promoter lies on a fitness plateau whereby even large changes in gene expression can be tolerated without a substantial loss of fitness.


Subject(s)
Gene Expression Regulation, Fungal , Genetic Fitness , Malate Synthase/genetics , Saccharomyces cerevisiae/genetics , DNA, Fungal/genetics , Evolution, Molecular , Genes, Fungal , Malate Synthase/biosynthesis , Promoter Regions, Genetic , Saccharomyces cerevisiae/enzymology , Saccharomyces cerevisiae/metabolism , Saccharomyces cerevisiae Proteins/biosynthesis , Saccharomyces cerevisiae Proteins/genetics , Transcription Factors/genetics , Transcriptional Activation
3.
Genet Res (Camb) ; 97: e2, 2015 Feb 23.
Article in English | MEDLINE | ID: mdl-26788801

ABSTRACT

Under the traditional mutation load model based on multiplicative fitness effects, the load in a population is 1-e-U , where U is the genomic deleterious mutation rate. Because this load becomes high under large U, synergistic epistasis has been proposed as one possible means of reducing the load. However, experiments on model organisms attempting to detect synergistic epistasis have often focused on a quadratic fitness model, with the resulting general conclusion being that epistasis is neither common nor strong. Here, I present a model of additive fitness effects and show that, unlike multiplicative effects, the equilibrium frequency of an allele under additivity is dependent on the average absolute fitness of the population. The additive model then results in a load of U/(U +1), which is much lower than 1-e-U for large U. Numerical iterations demonstrate that this analytic derivation holds as a good approximation under biologically relevant values of selection coefficients and U. Additionally, regressions onto Drosophila mutation accumulation data suggest that the common method of inferring epistasis by detecting large quadratic terms from regressions is not always necessary, as the additive model fits the data well and results in synergistic epistasis. Furthermore, the additive model gives a much larger reduction in load than the quadratic model when predicted from the same data, indicating that it is important to consider this additive model in addition to the quadratic model when inferring epistasis from mutation accumulation data.


Subject(s)
Drosophila melanogaster/genetics , Genetic Load , Models, Genetic , Models, Statistical , Mutation/genetics , Animals , Biological Evolution , Epistasis, Genetic
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