Stochastic gene expression and phenotypic variability in yeast adaptation
French National Research Agency (ANR)  
Funder: French National Research Agency (ANR)Project code: ANR-12-JSV6-0006
Funder Contribution: 119,995 EUR
This project aims at studying the role of gene expression variability (due to the stochastic fluctuations at the molecular level) in stress response and genetic instability. The impact of this variability on population dynamics is now well-studied, and increase of stochasticity (or noise) in gene expression is considered as a relevant evolutionary strategy in fluctuating environments. Here we want to determine if such an increase for some genes has been a way for technological yeast strains to adapt to the stressful fluctuating conditions they have to deal with. Indeed these strains are well-adapted to many environmental stress compared to laboratory strains. In the first part of this project, we will focus on the recently sequenced oenological strain of Saccharomyces cerevisiae EC1118 (NOVO et al. 2009) to detect promoters that are noisier in this strain compared to the standard non-adapted laboratory strain S288c. If such differences of noise are detected, we will study their impact on stress response and adaptation in stressful environments, especially in terms of fitness. This original stragety should enable the identification of new determinants of stress resistance and tolerance. At the moment no study has linked noise in gene expression to genetic variability. But, like any other phenotype, maintenance of genome integrity is under the influence of genes expressed with stochastic fluctuations. The rate of genetic-variant generation (RGVG) could be variable as a consequence of stochastic fluctuations in the expression of DNA repair and maintenance genes from cell-to-cell. High noise in the expression of genes involved in Double-Strand Break repair or DNA replication for instance, could confer a broad range RGVG from cell-to-cell in the population, and favour the emergence of sub-populations with higher genetic variability in times of stress, thanks to a second-order selection process (indirect selection of mutator strains along with favourable mutations they generate which counterbalance possible deleterious mutations) (CAPP, 2010). The aim of this project is to determine if industrial strains have evolved towards such a high noise in the expression of genes involved in DNA repair and maintenance. If this is the case, we will study the impact of different noise levels in the xepression of these genes on genetic variability under selective conditions. _x000D_ Capp, J. P. (2010). Noise-driven heterogeneity in the rate of genetic-variant generation as a basis for evolvability. Genetics 185, 395-404 _x000D_ Novo, M., et al. (2009). Eukaryote-to-eukaryote gene transfer events revealed by the genome sequence of the wine yeast Saccharomyces cerevisiae EC1118. Proc Natl Acad Sci U S A 106, 16333-16338.
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