Skip to main content
Log in

Genetic pleiotropy in Saccharomyces cerevisiae quantified by high-resolution phenotypic profiling

  • Original Paper
  • Published:
Molecular Genetics and Genomics Aims and scope Submit manuscript

Abstract

Genetic pleiotropy, the ability of a mutation in a single gene to give rise to multiple phenotypic outcomes, constitutes an important but incompletely understood biological phenomenon. We used a high-resolution and high-precision phenotypic profiling approach to quantify the fitness contribution of genes on the five smallest yeast chromosomes during different forms of environmental stress, selected to probe a wide diversity of physiological features. We found that the extent of pleiotropy is much higher than previously claimed; 17% of the yeast genes were pleiotropic whereof one-fifth were hyper-pleiotropic. Pleiotropic genes preferentially participate in functions related to determination of protein fate, cell growth and morphogenesis, signal transduction and transcription. Contrary to what has earlier been proposed we did not find experimental evidence for slower evolutionary rate of pleiotropic genes/proteins. We also refute the existence of phenotypic islands along chromosomes but report on a remarkable loss both of pleiotropy and of phenotypic penetrance towards chromosomal ends. Thus, the here reported features of pleiotropy both have implications on our understanding of evolutionary processes as well as the mechanisms underlying disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Altschul SF, Lipman DJ (1990) Protein database searches for multiple alignments. Proc Natl Acad Sci USA 87:5509–5513

    Article  PubMed  CAS  Google Scholar 

  • Caesar R, Blomberg A (2004) The stress-induced Tfs1p requires NatB-mediated acetylation to inhibit carboxypeptidase Y and to regulate the protein kinase A pathway. J Biol Chem 279:38532–38543

    Article  PubMed  CAS  Google Scholar 

  • Chautard H, Jacquet M, Schoentgen F, Bureaud N, Benedetti H (2004) Tfs1p, a member of the PEBP family, inhibits the Ira2p but not the Ira1p Ras GTPase-activating protein in Saccharomyces cerevisiae. Eukaryot Cell 3:459–470

    Article  PubMed  CAS  Google Scholar 

  • Cohen BA, Mitra RD, Hughes JD, Church GM (2000) A computational analysis of whole-genome expression data reveals chromosomal domains of gene expression. Nat Genet 26:183–186

    Article  PubMed  CAS  Google Scholar 

  • Davidson JN, Chen KC, Jamison RS, Musmanno LA, Kern CB (1993) The evolutionary history of the first three enzymes in pyrimidine biosynthesis. Bioessays 15:157–164

    Article  PubMed  CAS  Google Scholar 

  • Dudley A, Janse D, Tanay A, Shamir R, Church GM (2005) A global view on pleiotropy and phenotypically derived gene function in yeast. Mol Sys Biol 1:msb4100004–E4100001–msb4100004–E4100011

    Google Scholar 

  • Finlay BB, Falkow S (1997) Common themes in microbial pathogenicity revisited. Microbiol Mol Biol Rev 61:136–169

    PubMed  CAS  Google Scholar 

  • Fisher RA (1930) The genetical theory of natural selection. The Clarendon Press Oxford

    Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Gu Z, Steinmetz LM, Gu X, Scharfe C, Davis RW, Li WH (2003) Role of duplicate genes in genetic robustness against null mutations. Nature 421:63–66

    Article  PubMed  CAS  Google Scholar 

  • Hirsh AE, Fraser HB (2001) Protein dispensability and rate of evolution. Nature 411:1046–1049

    Article  PubMed  CAS  Google Scholar 

  • Hirsh AE, Fraser HB, Wall DP (2005) Adjusting for selection on synonymous sites in estimates of evolutionary distance. Mol Biol Evol 22:174–177

    Article  PubMed  CAS  Google Scholar 

  • Kamath RS, Ahringer J (2003) Genome-wide RNAi screening in Caenorhabditis elegans. Methods 30:313–321

    Article  PubMed  CAS  Google Scholar 

  • Kellis M, Patterson N, Endrizzi M, Birren B, Lander ES (2003) Sequencing and comparison of yeast species to identify genes and regulatory elements. Nature 423:241–254

    Article  PubMed  CAS  Google Scholar 

  • Lercher MJ, Blumenthal T, Hurst LD (2003) Coexpression of neighboring genes in Caenorhabditis elegans is mostly due to operons and duplicate genes. Genome Res 13:238–243

    Article  PubMed  CAS  Google Scholar 

  • Lercher MJ, Urrutia AO, Hurst LD (2002) Clustering of housekeeping genes provides a unified model of gene order in the human genome. Nat Genet 31:180–183

    Article  PubMed  CAS  Google Scholar 

  • Mewes HW et al (2002) MIPS: a database for genomes and protein sequences. Nucleic Acids Res 30:31–34

    Article  PubMed  CAS  Google Scholar 

  • Otto SP (2004) Two steps forward, one step back: the pleiotropic effects of favoured alleles. Proc Biol Sci 271:705–714

    Article  PubMed  Google Scholar 

  • Pal C, Hurst LD (2003) Evidence for co-evolution of gene order and recombination rate. Nat Genet 33:392–395

    Article  PubMed  CAS  Google Scholar 

  • Preisig-Muller R et al (2002) Heteromerization of Kir2.x potassium channels contributes to the phenotype of Andersen’s syndrome. Proc Natl Acad Sci USA 99:7774–7779

    Article  PubMed  CAS  Google Scholar 

  • Promislow DE (2004) Protein networks, pleiotropy and the evolution of senescence. Proc Biol Sci 271:1225–1234

    Article  PubMed  CAS  Google Scholar 

  • Singleton P, Sainsbury D (2001) Dictionary of microbiology and molecular biology, 3 edn. Wiley Baffins Lane

    Google Scholar 

  • Spellman PT, Rubin GM (2002) Evidence for large domains of similarly expressed genes in the Drosophila genome. J Biol 1:5

    Article  PubMed  Google Scholar 

  • Thatcher JW, Shaw JM, Dickinson WJ (1998) Marginal fitness contributions of nonessential genes in yeast. Proc Natl Acad Sci USA 95:253–257

    Article  PubMed  CAS  Google Scholar 

  • Wall DP et al (2005) Functional genomic analysis of the rates of protein evolution. Proc Natl Acad Sci USA 102:5483–5488

    Article  PubMed  CAS  Google Scholar 

  • Warringer J, Blomberg A (2003) Automated screening in environmental arrays allows analysis of quantitative phenotypic profiles in Saccharomyces cerevisiae. Yeast 20:53–67

    Article  PubMed  CAS  Google Scholar 

  • Warringer J, Ericson E, Fernandez L, Nerman O, Blomberg A (2003) High-resolution yeast phenomics resolves different physiological features in the saline response. Proc Natl Acad Sci USA 100:15724–15729

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Anders Blomberg.

Additional information

Communicated by A. Aguilera

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ericson, E., Pylvänäinen, I., Fernandez-Ricaud, L. et al. Genetic pleiotropy in Saccharomyces cerevisiae quantified by high-resolution phenotypic profiling. Mol Genet Genomics 275, 605–614 (2006). https://doi.org/10.1007/s00438-006-0112-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00438-006-0112-1

Keywords

Navigation