1. Stanford Genome Technology Center, Stanford University, Palo Alto, California 94304, USA
2. Department of Biochemistry, Stanford University School of Medicine, Stanford, California 94305-5307, USA
3. Department of Molecular, Cellular & Developmental Biology, Yale University, New Haven, Connecticut 06520-8103, USA
4. Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520-8103, USA
5. Department of Molecular Biology & Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2185, USA
6. Department of Genetics, Washington University Medical School, St Louis, Missouri 63110, USA
7. Department of Biology, McGill University, Montreal, Québec H3A 1B1, Canada
8. Rosetta Inpharmatics Inc., Kirkland, Washington 98034, USA
9. FYSA, Université catholique de Louvain, Place Croix du Sud, 2/20, 1348-Louvain-la-Neuve, Belgium
10. Université Libre de Bruxelles, Laboratoire de Physiologie Cellulaire, IBMM CP300, Gosselies, Belgium
11. Departments of Bioengineering and Chemistry, University of California, Berkeley, and Physical Biosciences Division, Lawrence Berkeley National Laboratory, Howard Hughes Medical Institute, Berkeley, California 94720-1770, USA
12. IRMW, Université Libre de Bruxelles, B-1070 Brussels, Belgium
13. Departamento de Microbiologia y Genetica, Instituto de Microbiologia y Bioquimica, CSIC/Universidad de Salamanca, E-37007 Salamanca, Spain
14. Department of Molecular Microbiology, Biozentrum, University of Basel, CH-4056 Basel, Switzerland
15. Department of Biology, University of Padova, I-35121 Padova, Italy
16. EUROSCARF, Johann Wolfgang Goethe-Universität, Institute of Microbiology, D-60439 Frankfurt/Main, Germany
17. Department of Electrical Engineering and Computer Sciences, University of California, Berkeley, California 94720-1770, USA
18. Gene Regulation and Chromosome Biology Laboratory, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, Maryland 21702, USA
19. Institut fur Mikrobiologie, Heinrich-Heine-Universitat Dusseldorf, D-40225 Dusseldorf, Germany
20. Institute of Biological Sciences, University of Wales, Aberystwyth, Wales SY23 3DA, UK
21. Department of Biology, Concordia University, Montreal, Québec H3G 1M8, Canada
22. Katholieke Universiteit Leuven, Laboratory of Gene Technology, B-3001 Leuven, Belgium

Correspondence to: Ronald W. Davis^1,2 Correspondence and requests for material should be addressed to R.W.D. (e-mail: Email: dbowe@cmgm.stanford.edu).

Abstract

Determining the effect of gene deletion is a fundamental approach to understanding gene function. Conventional genetic screens exhibit biases, and genes contributing to a phenotype are often missed. We systematically constructed a nearly complete collection of gene-deletion mutants (96% of annotated open reading frames, or ORFs) of the yeast Saccharomyces cerevisiae. DNA sequences dubbed 'molecular bar codes' uniquely identify each strain, enabling their growth to be analysed in parallel and the fitness contribution of each gene to be quantitatively assessed by hybridization to high-density oligonucleotide arrays. We show that previously known and new genes are necessary for optimal growth under six well-studied conditions: high salt, sorbitol, galactose, pH 8, minimal medium and nystatin treatment. Less than 7% of genes that exhibit a significant increase in messenger RNA expression are also required for optimal growth in four of the tested conditions. Our results validate the yeast gene-deletion collection as a valuable resource for functional genomics.