Stochastic gene expression and phenotypic variability in yeast adaptation – NOISYEAST

We used a genome wide approach to identify sequences conferring high level of noise in the sequenced oenological Saccharomyces cerevisiae strain EC1118. A Green Fluorescent Protein (GFP)-fused genomic library has been created. The yeast population containing this library were enriched for sequences conferring high level of noise in gene expression by several rounds of fluctuating selection for GFP expression using cell sorting (7 rounds of sorting of cells with alternatively the highest or the lowest fluorescence level that are kept). Analysis of individual clones revealed such an enrichment and 98 genomic fragments giving high noise in expression have been sequenced.

Most of the sequenced genomic fragments correspond to genes involved in stress response or related to other environmental factors. Analysis of these fragments reveals many genetic variations compared to their counterpart in the sequenced laboratory strain S288c. We selected some of these fragments for further investigations because we hypothesize that these variations could possibly generate differences of noise levels. Indeed such variations in gene expression profiles between S. cerevisiae strains could have been selected thanks to the benefit conferred by expression heterogeneity in the stressful and fluctuating conditions frequently experimented by technological strains. We have shown that at least for one gene, the genetic variations indeed generate more noise.

This work identifies for the first time natural genetic variations in yeast conferring different levels of noise in gene expression. This result reinforces the hypothesis of a possible adaptation through modulation of noise. Now we aim at determining if increase noise in the expression of the gene we identified confers better resistance and adatation in stressful conditions. This could lead to noise-based genetic engineering to improve the behaviour of yeast in industrial processes.

Oral conference : «Promoter-mediated transcriptional noise, phenotypic variability and budding yeast adaptation to environmental stresses«, Gordon Research Conference “Biological Mechanisms in Evolution”, Stonehill College, Juin 2013.

No article or patent for the moment.

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.
Capp, J. P. (2010). Noise-driven heterogeneity in the rate of genetic-variant generation as a basis for evolvability. Genetics 185, 395-404
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.