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

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 ph enotypic analysis on yeast strains deleted for functionally orphan genes. T o this end we set up a simple approach to detect growth defects of a relati vely large number of strains in the presence of osmolytes, ethanol, high te mperature, inhibitory compounds or drugs affecting protein biosynthesis, ph osphorylation level or nucleic acids biosynthesis. We have now developed th is procedure to a semi-quantitative level, we have included new inhibitors, such as hygromycin B, benomyl, metals and additional drugs interfering wit h synthesis of nucleic acids, and we have performed phenotypic analysis on the deleted strains of 564 genes poorly characterized in respect to their c ellular functions. About 30%, of the deleted strains showed at least one ph enotype: many of them were pleiotropic. For many gene deletions, the linkag e between the deletion marker and the observed phenotype(s) was studied by tetrad analysis and their co-segregation was demonstrated. Co-segregation w as found in about two-thirds of the analysed strains showing phenotype(s). Copyright (C) 2001 John Wiley & Sons, Ltd.