Large‐scale phenotypic analysis reveals identical contributions to cell functions of known and unknown yeast genes

Abstract

Sequencing of the yeast genome has shown that about one-third of the yeast ORFs code for unknown proteins. Many other have similarity to known genes, but still the cellular functions of the gene products are unknown. The aim of the B1 Consortium of the EUROFAN project was to perform a qualitative phenotypic analysis on yeast strains deleted for functionally orphan genes. To this end we set up a simple approach to detect growth defects of a relatively large number of strains in the presence of osmolytes, ethanol, high temperature, inhibitory compounds or drugs affecting protein biosynthesis, phosphorylation level or nucleic acids biosynthesis. We have now developed this procedure to a semi-quantitative level, we have included new inhibitors, such as hygromycin B, benomyl, metals and additional drugs interfering with synthesis of nucleic acids, and we have performed phenotypic analysis on the deleted strains of 564 genes poorly characterized in respect to their cellular functions. About 30% of the deleted strains showed at least one phenotype: many of them were pleiotropic. For many gene deletions, the linkage between the deletion marker and the observed phenotype(s) was studied by tetrad analysis and their co-segregation was demonstrated. Co-segregation was found in about two-thirds of the analysed strains showing phenotype(s).

Interactions Between Stressful Environment and Gene Deletions Alleviate the Expected Average Loss of Fitness in Yeast

“…The final environment used in this study is 0.8 mm caffeine. This compound alters the activity of PKA, Tor1, and Pkc1, important regulators of cell metabolism, and influences the stability of chromosomes and the trafficking of proteins through Golgi and vacuole biogenesis (Bianchi et al 2001;Levin 2005;Kuranda et al 2006). It likely represents an artificial metabolic stress, one that, in contrast to deprivation of nutrients, heat, or salinity, was not routinely encountered by the yeast in its evolutionary past.…”

A novel mechanism regulates H2S and SO2 production in Saccharomyces cerevisiae

“…It has also been reported that the skp2 mutant is sensitive to azaserine (Bianchi et al, 2001), suggesting that Skp2p interacts with Ser33p and may modulate serine biosynthesis. Ser33p encodes a phosphoglycerate dehydrogenase (Albers et al 2003).…”

Dual functions of Mdt1 in genome maintenance and cell integrity pathways in Saccharomyces cerevisiae

“…Similarly to mdt1 , mdt1-RRM0 resulted in a severe synthetic viability defect in combination with slt2 ( Figure 5B). 5. mdt1-RRM0 shares the extreme CsCl hypersensitivity of mdt1 (Figure 2), a phenotype previously identified in a large-scale screen but where the underlying cellular defect is not well understood (Bianchi et al, 2001).…”