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PMID: 18420932 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

The chemical genomic portrait of yeast: uncovering a phenotype for all genes.

Science (New York, N.Y.) ·Vol. 320 ·No. 5874 ·2008-04-18 ·Pages 362-5

Hillenmeyer ME, Fung E, Wildenhain J, Pierce SE, Hoon S, Lee W, Proctor M, St Onge RP, Tyers M, Koller D, Altman RB, Davis RW, Nislow C, Giaever G

Abstract

Genetics aims to understand the relation between genotype and phenotype. However, because complete deletion of most yeast genes ( approximately 80%) has no obvious phenotypic consequence in rich medium, it is difficult to study their functions. To uncover phenotypes for this nonessential fraction of the genome, we performed 1144 chemical genomic assays on the yeast whole-genome heterozygous and homozygous deletion collections and quantified the growth fitness of each deletion strain in the presence of chemical or environmental stress conditions. We found that 97% of gene deletions exhibited a measurable growth phenotype, suggesting that nearly all genes are essential for optimal growth in at least one condition.

MeSH Terms
Culture Media Drug Resistance, Multiple, Fungal Gene Deletion Genes, Essential Genes, Fungal Genes, MDR Genome, Fungal Genomics Heterozygote Homozygote Metabolic Networks and Pathways/drug effects Multigene Family Phenotype Saccharomyces cerevisiae/drug effects,genetics,growth & development,physiology Saccharomyces cerevisiae Proteins/genetics,metabolism Signal Transduction Small Molecule Libraries/pharmacology
Chemicals
Culture Media Saccharomyces cerevisiae Proteins Small Molecule Libraries
Authors & Affiliations
14 authors, click to expand affiliations / ORCID
Hillenmeyer Maureen E
Stanford Genome Technology Center, Stanford University, Palo Alto, CA 94304, USA.
Fung Eula
Wildenhain Jan
Pierce Sarah E
Hoon Shawn
Lee William
Proctor Michael
St Onge Robert P
Tyers Mike
Koller Daphne
Altman Russ B
Davis Ronald W
Nislow Corey
Giaever Guri
References (28)
28 references, click to expand
  1. Subcellular localization and activity of multidrug resistance proteins.
    Mol Biol Cell. 2003 Aug;14(8):3389-99 PMID: 12925771
  2. Role of duplicate genes in genetic robustness against null mutations.
    Nature. 2003 Jan 2;421(6918):63-6 PMID: 12511954
  3. From large networks to small molecules.
    Curr Opin Chem Biol. 2004 Feb;8(1):81-90 PMID: 15036161
  4. GO::TermFinder--open source software for accessing Gene Ontology information and finding significantly enriched Gene Ontology terms associated with a list of genes.
    Bioinformatics. 2004 Dec 12;20(18):3710-5 PMID: 15297299
  5. Multiple knockout analysis of genetic robustness in the yeast metabolic network.
    Nat Genet. 2006 Sep;38(9):993-8 PMID: 16941010
  6. Genome-wide responses to DNA-damaging agents.
    Annu Rev Microbiol. 2005;59:357-77 PMID: 16153173
  7. Transcriptional networks: reverse-engineering gene regulation on a global scale.
    Curr Opin Microbiol. 2004 Dec;7(6):638-46 PMID: 15556037
  8. Receptor downregulation and multivesicular-body sorting.
    Nat Rev Mol Cell Biol. 2002 Dec;3(12):893-905 PMID: 12461556
  9. Small molecules: the missing link in the central dogma.
    Nat Chem Biol. 2005 Jul;1(2):64-6 PMID: 16407997
  10. Separate roles for the Golgi apparatus and lysosomes in the sequestration of drugs in the multidrug-resistant human leukemic cell line HL-60.
    J Biol Chem. 2003 Dec 12;278(50):50234-9 PMID: 14522995
  11. Global mapping of the yeast genetic interaction network.
    Science. 2004 Feb 6;303(5659):808-13 PMID: 14764870
  12. Integration of chemical-genetic and genetic interaction data links bioactive compounds to cellular target pathways.
    Nat Biotechnol. 2004 Jan;22(1):62-9 PMID: 14661025
  13. Functional characterization of the S. cerevisiae genome by gene deletion and parallel analysis.
    Science. 1999 Aug 6;285(5429):901-6 PMID: 10436161
  14. A high-resolution map of transcription in the yeast genome.
    Proc Natl Acad Sci U S A. 2006 Apr 4;103(14):5320-5 PMID: 16569694
  15. A global view of pleiotropy and phenotypically derived gene function in yeast.
    Mol Syst Biol. 2005;1:2005.0001 PMID: 16729036
  16. Chemogenomic profiling: identifying the functional interactions of small molecules in yeast.
    Proc Natl Acad Sci U S A. 2004 Jan 20;101(3):793-8 PMID: 14718668
  17. The yeast multidrug transporter Pdr5 of the plasma membrane is ubiquitinated prior to endocytosis and degradation in the vacuole.
    FEBS Lett. 1996 Jan 8;378(2):177-81 PMID: 8549828
  18. A proteomic analysis of lysosomal integral membrane proteins reveals the diverse composition of the organelle.
    Mol Cell Proteomics. 2005 Feb;4(2):133-43 PMID: 15579476
  19. Metabolic network analysis of the causes and evolution of enzyme dispensability in yeast.
    Nature. 2004 Jun 10;429(6992):661-4 PMID: 15190353
  20. Proof and evolutionary analysis of ancient genome duplication in the yeast Saccharomyces cerevisiae.
    Nature. 2004 Apr 8;428(6983):617-24 PMID: 15004568
  21. Analysis of the tangled relationships between P-glycoprotein-mediated multidrug resistance and the lipid phase of the cell membrane.
    Eur J Biochem. 2000 Jan;267(2):277-94 PMID: 10632698
  22. Yeast ABC transporters-- a tale of sex, stress, drugs and aging.
    FEBS Lett. 2006 Feb 13;580(4):1131-8 PMID: 16406363
  23. Functional profiling of the Saccharomyces cerevisiae genome.
    Nature. 2002 Jul 25;418(6896):387-91 PMID: 12140549
  24. Mechanisms of haploinsufficiency revealed by genome-wide profiling in yeast.
    Genetics. 2005 Apr;169(4):1915-25 PMID: 15716499
  25. Mammalian peroxisomes and reactive oxygen species.
    Histochem Cell Biol. 2004 Oct;122(4):383-93 PMID: 15241609
  26. Exploring the mode-of-action of bioactive compounds by chemical-genetic profiling in yeast.
    Cell. 2006 Aug 11;126(3):611-25 PMID: 16901791
  27. Pharmacogenomic analysis: correlating molecular substructure classes with microarray gene expression data.
    Pharmacogenomics J. 2002;2(4):259-71 PMID: 12196914
  28. Endocytic recycling compartments altered in cisplatin-resistant cancer cells.
    Cancer Res. 2006 Feb 15;66(4):2346-53 PMID: 16489040
Article Info
Journal
Science (New York, N.Y.)
Abbr.
Science
ISSN
1095-9203
Published
2008-04-18
Pages
362-5
Language
English
Region
United States
NLM ID
0404511
PMCID
PMC2794835
Subset
IM
Grants
NIGMS NIH HHS · U01 GM061374 · United States
NIGMS NIH HHS · U01 GM061374-09 · United States
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