Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Identification and characterization of high-flux-control genes of yeast through competition analyses in continuous cultures

Abstract

Using competition experiments in continuous cultures grown in different nutrient environments (glucose limited, ammonium limited, phosphate limited and white grape juice), we identified genes that show haploinsufficiency phenotypes (reduced growth rate when hemizygous) or haploproficiency phenotypes (increased growth rate when hemizygous). Haploproficient genes (815, 1,194, 733 and 654 in glucose-limited, ammonium-limited, phosphate-limited and white grape juice environments, respectively) frequently show that phenotype in a specific environmental context. For instance, genes encoding components of the ubiquitination pathway or the proteasome show haploproficiency in nitrogen-limited conditions where protein conservation may be beneficial. Haploinsufficiency is more likely to be observed in all environments, as is the case with genes determining polar growth of the cell. Haploproficient genes seem randomly distributed in the genome, whereas haploinsufficient genes (685, 765, 1,277 and 217 in glucose-limited, ammonium-limited, phosphate-limited and white grape juice environments, respectively) are over-represented on chromosome III. This chromosome determines a yeast's mating type, and the concentration of haploinsufficient genes there may be a mechanism to prevent its loss.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Distribution of growth rate differences in glucose-limited medium (red), ammonium-limited medium (blue), phosphate-limited medium (green) and grape juice (pink).
Figure 2: Comparison of haploinsufficient and proficient phenotypes in the different media.
Figure 3: The 26S proteasome, adapted from the KEGG pathway database (see URLs section in Methods).
Figure 4

Similar content being viewed by others

References

  1. Oliver, S.G. From genomes to systems: the path with yeast. Phil. Trans. R. Soc. Lond. B 361, 477–482 (2006).

    Article  CAS  Google Scholar 

  2. Kacser, H. & Burns, J.A. The control of flux. Symp. Soc. Exp. Biol. 27, 65–104 (1973).

    CAS  PubMed  Google Scholar 

  3. Heinrich, R. & Rapoport, T.A. A linear steady-state treatment of enzymatic chains. General properties, control and effector strength. Eur. J. Biochem. 42, 89–95 (1974).

    Article  CAS  Google Scholar 

  4. Castrillo, J.I. et al. Growth control of the eukaryote cell: a systems biology study in yeast. J. Biol. 6, 4 (2007).

    Article  Google Scholar 

  5. Winzeler, E.A. et al. Functional characterization of the S. cerevisiae genome by gene deletion and parallel analysis. Science 285, 901–906 (1999).

    Article  CAS  Google Scholar 

  6. Goffeau, A. et al. Life with 6000 genes. Science 274, 563–567 (1996).

    Article  Google Scholar 

  7. Mortimer, R.K., Romano, P., Suzzi, G. & Polsinelli, M. Genome renewal: a new phenomenon revealed from a genetic study of 43 strains of Saccharomyces cerevisiae derived from natural fermentation of grape musts. Yeast 10, 1543–1552 (1994).

    Article  CAS  Google Scholar 

  8. Veitia, R.A. Exploring the etiology of haploinsufficiency. Bioessays 24, 175–184 (2002).

    Article  CAS  Google Scholar 

  9. Paquin, C. & Adams, J. Frequency of fixation of adaptive mutations is higher in evolving diploid than haploid yeast populations. Nature 302, 495–500 (1983).

    Article  CAS  Google Scholar 

  10. Ashburner, M. et al. Gene Ontology: tool for the unification of biology. Nat. Genet. 25, 25–29 (2000).

    Article  CAS  Google Scholar 

  11. Eason, R.G. et al. Characterization of synthetic DNA bar codes in Saccharomyces cerevisiae gene-deletion strains. Proc. Natl. Acad. Sci. USA 101, 11046–11051 (2004).

    Article  CAS  Google Scholar 

  12. Giaever, G. et al. Functional profiling of the Saccharomyces cerevisiae genome. Nature 418, 387–391 (2002).

    Article  CAS  Google Scholar 

  13. Deutschbauer, A.M. et al. Mechanisms of haploinsufficiency revealed by genome-wide profiling in yeast. Genetics 169, 1915–1925 (2005).

    Article  CAS  Google Scholar 

  14. Doniger, S.W. et al. MAPPFinder: using Gene Ontology and GenMAPP to create a global gene-expression profile from microarray data. Genome Biol. 4, R7 (2003).

    Article  Google Scholar 

  15. Zeeberg, B.R. et al. GoMiner: a resource for biological interpretation of genomic and proteomic data. Genome Biol. 4, R28 (2003).

    Article  Google Scholar 

  16. Glover, C.V. III. On the physiological role of casein kinase II in Saccharomyces cerevisiae. Prog. Nucleic Acid Res. Mol. Biol. 59, 95–133 (1998).

    Article  CAS  Google Scholar 

  17. Oliver, S.G. Classical yeast biotechnology. in Biotechnology Handbooks – Saccharomyces (eds. Tuite, M.F. & Oliver, S.G.) 213–248 (Plenum, New York, 1991).

    Chapter  Google Scholar 

  18. Sherman, F., Fink, G.R. & Hicks, J.B. Methods in Yeast Genetics. (Cold Spring Harbor Press, Cold Spring Harbor, New York, 1981).

  19. Baganz, F. et al. Quantitative analysis of yeast gene function using competition experiments in continuous culture. Yeast 14, 1417–1427 (1998).

    Article  CAS  Google Scholar 

  20. Colson, I., Delneri, D. & Oliver, S.G. Effects of reciprocal translocations on the fitness of Saccharomyces cerevisiae. EMBO Rep. 5, 392–398 (2004).

    Article  CAS  Google Scholar 

  21. Benjamini, Y. & Hochberg, Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J. Roy. Stat. Soc. Ser. B 57, 289–300 (1995).

    Google Scholar 

Download references

Acknowledgements

This work was supported by grants from the Natural Environment Research Council (NERC) to S.G.O., G.G. and D.B.K., and by the Consortion for the Functional Genomics of Microbial Eukaryotes (COGEME; Coordinator, S.G.O.), funded by the Investigating Gene Function Initiative of the Biotechnology and Biological Sciences Research Council (BBSRC), and a BBSRC project grant to S.G.O. and D.B.K. D.D. is a NERC Advanced Fellow. K.G. holds a Wellcome Trust PhD studentship. We thank C. Reeves, P. Pir, J. Wu and M. Barton for communicating their unpublished data. We thank T. Carr (Sussex), D. Charlesworth (Edinburgh), L. Hurst (Bath) and B. Papp (Szeged) for stimulating discussions.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Stephen G Oliver.

Supplementary information

Supplementary Text and Figures

Supplementary Methods, Supplementary Note, Supplementary Figure 1 (PDF 559 kb)

Supplementary Table 1

List of strains whose TAGs give weak signal (XLS 18 kb)

Supplementary Table 2

List of strains lost in batch culture (XLS 12 kb)

Supplementary Table 3

Strains showing severe haploinsufficiency (XLS 25 kb)

Supplementary Table 4

Strains showing haploinsufficiency or haploproficiency in all conditions (XLS 545 kb)

Supplementary Table 5

Nitrogen content of grape juice and the chemically defined media (XLS 20 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Delneri, D., Hoyle, D., Gkargkas, K. et al. Identification and characterization of high-flux-control genes of yeast through competition analyses in continuous cultures. Nat Genet 40, 113–117 (2008). https://doi.org/10.1038/ng.2007.49

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng.2007.49

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing