Project description:Genetic interaction network has a very limited impact on the evolutionary trajectories in continuous culture-grown populations of yeast
Project description:Transcriptional profiling of Saccharomyces cerevisiae cells comparing the W303-1A wildtype with the W303-1A double mutant for MSN2 and MSN4 during zinc deficient conditions Keywords: Genetic modification with zinc limitation Two condition experiment, W303-1A vs W303-1A delta MSN2, MSN4. Biological replicates: 2 wildtype, 2 knock-out, independently grown and harvested.
Project description:Background: The impact of genetic interaction networks on evolution is a fundamental issue. Previous studies have demonstrated that the topology of the network is determined by the properties of the cellular machinery. Functionally related genes frequently interact with one another, and they establish modules, e.g., modules of protein complexes and biochemical pathways. In this study, we experimentally tested the hypothesis that compensatory evolutionary modifications, such as mutations and transcriptional changes, occur frequently in genes from perturbed modules of genetically interacting genes. Results: Using haploid strains of Saccharomyces cerevisiae deletion mutants as a model, we investigated two modules lacking COG7 or NUP133, which are evolutionarily conserved genes with many compensatory interactions. We performed laboratory evolution experiments with strains bearing these mutations in two genetic backgrounds (with or without additional deletion of MSH2), subjecting them to continuous culture in a non-limiting minimal medium. Next, the evolved yeast populations were characterized through whole-genome sequencing and transcriptome analyses. No obvious compensatory changes resulting from inactivation of genes already included in modules were identified. The supposedly compensatory inactivation of genes in the evolved strains was only rarely observed to be in accordance with the established fitness effect of the genetic interaction network. In fact, a substantial majority of the gene inactivations were predicted to be neutral. Similarly, transcriptome changes during continuous culture mostly signified adaptation to growth conditions rather than compensation of the absence of COG7, NUP133 or MSH2 genes. Conclusions: Our findings demonstrate that the genetic interactions and modular structure of the network described in other studies have very limited effects on the evolutionary trajectory observed on the genomic and transcriptomic levels, following gene deletion of module elements and upon our experimental conditions. This observation indicates that the modular structure of the cellular machinery has no impact on compensatory evolution in the short term.
Project description:Transcriptional profiling of Saccharomyces cerevisiae cells comparing the W303-1A wildtype with the W303-1A double mutant for MSN2 and MSN4 during zinc deficient conditions Keywords: Genetic modification with zinc limitation
Project description:A network governing DNA integrity was identified in yeast by a global genetic analysis of synthetic fitness or lethality defect (SFL) interactions. Within this network, multiple functional modules or mini-pathways were defined according to their common patterns of global SFL interactions and available protein-protein interaction information. Modules or genes involved in DNA replication, DNA replication checkpoint signaling, and oxidative stress response were identified as the major guardians against lethal spontaneous DNA damage, efficient repair of which requires the functions of the DNA damage checkpoint signaling and multiple DNA repair pathways. This genome-wide genetic interaction network also revealed potential roles of a number of genes and modules in mitotic DNA replication and maintenance of genomic stability. These include DIA2, NPT1, HST3, HST4, and the CSM1/LRS4 module (CSM1m). Likewise, the CTF18 module (CTF18m), previously implicated in sister chromatid cohesion, was found to participate in the DNA replication checkpoint. Keywords: dose response
Project description:We propose a carbon source dependent genetic regulatory network for the budding yeast Saccharomyces cerevisiae, derived from quantitative proteomic analyses integrated with bioinformatics knowledge of regulatory pathways and protein interactions. The proposed network, comprising 1247 transcription factor interactions and 126 chaperone interactions, defines the proteome shift in the cell when growing under different carbon sources. We used a label-free proteomics strategy to quantify alterations in protein abundance for S. cerevisiae when grown on minimal media using glucose, galactose, maltose and trehalose as sole carbon sources.