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Functional profiling of theSaccharomyces cerevisiae genome

Naturevolume 418, pages387–391 (2002)Cite this article

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 yeastSaccharomyces 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.

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Figure 1: TheKanMX deletion cassette module.
Figure 2: Growth of deletion strains exhibiting reduced fitness in galactose medium.
Figure 3: Clustering of genes required for growth in conditions of high osmolarity.
Figure 4: Comparison of expression and fitness profiling data.
Figure 5: The seven phenotypic categories of deletion mutant morphologies.

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Acknowledgements

We thank I. Bastiaens, J. Howard Dees, R. Diaz, F. Dietrich, K. Freidel, N. Liebundguth, C. Rebischong, R. Schiavon, J. Schneider, T. Verhoeven and R. Wysoki for technical assistance. G.G. thanks C. Nislow for critical readings of the manuscript. This work was primarily supported by grants from the European Commission and the National Human Genome Research Institute (USA), the Medical Research Council of Canada, and the Swiss Office for Science.

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Authors and Affiliations

  1. Stanford Genome Technology Center, Stanford University, Palo Alto, California, 94304, USA

    Guri Giaever, Keith Anderson, Karen Davis, Zelek Herman, Daniel F. Jaramillo & Ronald W. Davis

  2. Department of Biochemistry, Stanford University School of Medicine, Stanford, California, 94305-5307, USA

    Angela M. Chu, Anna Astromoff, Adam Deutschbauer, Hong Liang, Daniel D. Shoemaker, Elizabeth A. Winzeler, Grace Yen & Ronald W. Davis

  3. Department of Molecular, Cellular & Developmental Biology, Yale University, New Haven, Connecticut, 06520-8103, USA

    Li Ni, Rhonda Bangham, Darlene LaBonte, Hong Liao, Lucy Liu, Chuanyun Luo, Petra Ross-Macdonald, Yonghong Yang & Michael Snyder

  4. Developmental Biology, Yale University,

    Li Ni, Rhonda Bangham, Darlene LaBonte, Hong Liao, Lucy Liu, Chuanyun Luo, Petra Ross-Macdonald, Yonghong Yang & Michael Snyder

  5. Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut, 06520-8103, USA

    Mark Gerstein & Ning Lan

  6. Department of Molecular Biology & Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205-2185, USA

    Carla Connelly, Rong Mao, Siew Loon Ooi, Sharon Sookhai-Mahadeo, Elaine Youngman, Kexin Yu & Jef D. Boeke

  7. Genetics, Johns Hopkins University School of Medicine,

    Carla Connelly, Rong Mao, Siew Loon Ooi, Sharon Sookhai-Mahadeo, Elaine Youngman, Kexin Yu & Jef D. Boeke

  8. Department of Genetics, Washington University Medical School, St Louis, Missouri, 63110, USA

    Linda Riles, Matt Curtiss, Julie Wilhelmy & Mark Johnston

  9. Department of Biology, McGill University, Montreal, Québec, H3A 1B1, Canada

    Steeve Véronneau, Marc Lussier, Patrice Menard & Howard Bussey

  10. Rosetta Inpharmatics Inc., Washington, 98034, Kirkland, USA

    Sally Dow, Christopher J. Roberts, Greg Schimmack & Teresa R. Ward

  11. FYSA, Université catholique de Louvain, Place Croix du Sud, 2/20, 1348, Louvain-la-Neuve, Belgium

    Ankuta Lucau-Danila & Francoise Foury

  12. Université Libre de Bruxelles, Laboratoire de Physiologie Cellulaire, IBMM CP300, Gosselies, Belgium

    Bruno André

  13. Departments of Bioengineering and Chemistry, University of California, Berkeley

    Adam P. Arkin & Patrick Flaherty

  14. Physical Biosciences Division, Lawrence Berkeley National Laboratory, Howard Hughes Medical Institute, California, 94720-1770, Berkeley, USA

    Adam P. Arkin & Patrick Flaherty

  15. IRMW, Université Libre de Bruxelles, Brussels, B-1070, Belgium

    Mohamed El Bakkoury & Bart Scherens

  16. Departamento de Microbiologia y Genetica, Instituto de Microbiologia y Bioquimica, CSIC/Universidad de Salamanca, E-37007, Salamanca, Spain

    Rocio Benito & Jose L. Revuelta

  17. Department of Molecular Microbiology, Biozentrum, University of Basel, CH-4056, Basel, Switzerland

    Sophie Brachat & Peter Philippsen

  18. Department of Biology, University of Padova, I-35121, Padova, Italy

    Stefano Campanaro & Giorgio Valle

  19. EUROSCARF, Johann Wolfgang Goethe-Universität, Institute of Microbiology, Frankfurt/Main, D-60439, Germany

    Karl-Dieter Entian, Svenja Hempel, Peter Kötter & Matthias Rose

  20. Department of Electrical Engineering and Computer Sciences, University of California, Berkeley, California, 94720-1770, USA

    Patrick Flaherty

  21. Gene Regulation and Chromosome Biology Laboratory, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, Maryland, 21702, USA

    David J. Garfinkel, Deanna Gotte, Brenda Shafer, Jeffrey N. Strathern & Ching-yun Wang

  22. Institut fur Mikrobiologie, Heinrich-Heine-Universitat Dusseldorf, Dusseldorf, D-40225, Germany

    Ulrich Güldener & Johannes H. Hegemann

  23. Institute of Biological Sciences, University of Wales, UK, Aberystwyth, Wales, SY23 3DA

    Diane E. Kelly, Steven L. Kelly & David C. Lamb

  24. Department of Biology, Concordia University, Canada, Montreal, Québec, H3G 1M8

    Reginald K. Storms

  25. Katholieke Universiteit Leuven, Laboratory of Gene Technology, Leuven, B-3001, Belgium

    Marleen Voet & Guido Volckaert

Authors
  1. Guri Giaever

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  2. Angela M. Chu

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  3. Li Ni

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  4. Carla Connelly

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  5. Linda Riles

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  6. Steeve Véronneau

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  7. Sally Dow

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  8. Ankuta Lucau-Danila

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  9. Keith Anderson

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  10. Bruno André

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  11. Adam P. Arkin

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  12. Anna Astromoff

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  13. Mohamed El Bakkoury

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  14. Rhonda Bangham

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  15. Rocio Benito

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  16. Sophie Brachat

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  17. Stefano Campanaro

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  18. Matt Curtiss

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  19. Karen Davis

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  20. Adam Deutschbauer

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  21. Karl-Dieter Entian

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  22. Patrick Flaherty

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  23. Francoise Foury

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  24. David J. Garfinkel

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  25. Mark Gerstein

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  26. Deanna Gotte

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  27. Ulrich Güldener

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  28. Johannes H. Hegemann

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  29. Svenja Hempel

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  30. Zelek Herman

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  31. Daniel F. Jaramillo

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  32. Diane E. Kelly

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  33. Steven L. Kelly

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  34. Peter Kötter

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  35. Darlene LaBonte

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  36. David C. Lamb

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  37. Ning Lan

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  38. Hong Liang

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  39. Hong Liao

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  40. Lucy Liu

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  41. Chuanyun Luo

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  42. Marc Lussier

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  43. Rong Mao

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  44. Patrice Menard

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  45. Siew Loon Ooi

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  46. Jose L. Revuelta

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  47. Christopher J. Roberts

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  48. Matthias Rose

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  49. Petra Ross-Macdonald

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  50. Bart Scherens

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  51. Greg Schimmack

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  52. Brenda Shafer

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  53. Daniel D. Shoemaker

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  54. Sharon Sookhai-Mahadeo

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  55. Reginald K. Storms

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  56. Jeffrey N. Strathern

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  57. Giorgio Valle

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  58. Marleen Voet

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  59. Guido Volckaert

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  60. Ching-yun Wang

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  61. Teresa R. Ward

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  62. Julie Wilhelmy

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  63. Elizabeth A. Winzeler

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  64. Yonghong Yang

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  65. Grace Yen

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  66. Elaine Youngman

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  67. Kexin Yu

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  68. Howard Bussey

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  69. Jef D. Boeke

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  70. Michael Snyder

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  71. Peter Philippsen

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  72. Ronald W. Davis

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  73. Mark Johnston

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Corresponding author

Correspondence toRonald W. Davis.

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The authors declare that they have no competing financial interests.

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Giaever, G., Chu, A., Ni, L.et al. Functional profiling of theSaccharomyces cerevisiae genome.Nature418, 387–391 (2002). https://doi.org/10.1038/nature00935

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