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.

  • Article
  • Published:

Hsp90 as a capacitor of phenotypic variation

Nature volume 417, pages 618–624 (2002)Cite this article

Abstract

Heat-shock protein 90 (Hsp90) chaperones the maturation of many regulatory proteins and, in the fruitfly Drosophila melanogaster, buffers genetic variation in morphogenetic pathways. Levels and patterns of genetic variation differ greatly between obligatorily outbreeding species such as fruitflies and self-fertilizing species such as the plant Arabidopsis thaliana. Also, plant development is more plastic, being coupled to environmental cues. Here we report that, in Arabidopsis accessions and recombinant inbred lines, reducing Hsp90 function produces an array of morphological phenotypes, which are dependent on underlying genetic variation. The strength and breadth of Hsp90's effects on the buffering and release of genetic variation suggests it may have an impact on evolutionary processes. We also show that Hsp90 influences morphogenetic responses to environmental cues and buffers normal development from destabilizing effects of stochastic processes. Manipulating Hsp90's buffering capacity offers a tool for harnessing cryptic genetic variation and for elucidating the interplay between genotypes, environments and stochastic events in the determination of phenotype.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Figure 1: Common GDA-dependent phenotypes in Shadara, Col and Ler accessions.
Figure 2: The same RI line-specific phenotypes are uncovered when buffering capacity is challenged by GDA (middle) and by growth at 27 °C (right).
Figure 3: The effect of GDA on developmental plasticity responses differs between 50 Cvi/Ler RI lines and their parents.
Figure 4: F1 progeny of accession crosses exhibit higher diversity and greater phenotype complexity than parental accessions, especially with GDA.
Figure 5: F1 progeny grow more robustly in the presence of 2 µM GDA than do parental accessions.

Similar content being viewed by others

References

  1. Waddington, C. H. Canalization of development and the inheritance of acquired characters. Nature 150, 563–565 (1942)

    Article  ADS  Google Scholar 

  2. Mather, K. Genetical control of stability in development. Heredity 7, 297–336 (1953)

    Article  Google Scholar 

  3. Durrant, A. The environmental induction of heritable change in Linum. Heredity 17, 27–61 (1962)

    Article  Google Scholar 

  4. McLaren, A. Too late for the midwife toad: stress, variability and Hsp90. Trends Genet. 15, 169–171 (1999)

    Article  CAS  Google Scholar 

  5. Waddington, C. H. Genetic assimilation of an acquired character. Evolution 7, 118–126 (1952)

    Article  Google Scholar 

  6. Rutherford, S. L. & Lindquist, S. Hsp90 as a capacitor for morphological evolution. Nature 396, 336–342 (1998)

    Article  CAS  ADS  Google Scholar 

  7. Buchner, J. Hsp90 & Co.—a holding for folding. Trends Biochem. Sci. 24, 136–141 (1999)

    Article  CAS  Google Scholar 

  8. Mayer, M. P. & Bukau, B. Molecular chaperones: the busy life of Hsp90. Curr. Biol. 9, R322–R325 (1999)

    Article  CAS  Google Scholar 

  9. Young, J. C., Moarefi, I. & Hartl, F. U. Hsp90: a specialized but essential protein-folding tool. J. Cell Biol. 154, 267–274 (2001)

    Article  CAS  Google Scholar 

  10. Abbott, R. J. & Gomes, M. F. Population genetic structure and outcrossing rate of Arabidopsis thaliana (L.) Heynh. Heredity 62, 411–418 (1989)

    Article  Google Scholar 

  11. Kuittinen, H., Mattila, A. & Savolainen, O. Genetic variation at marker loci and in quantitative traits in natural populations of Arabidopsis thaliana. Heredity 79, 144–152 (1997)

    Article  Google Scholar 

  12. Callahan, H. S., Pigliucci, M. & Schlichting, C. D. Developmental phenotypic plasticity: where ecology and evolution meet molecular biology. Bioessays 19, 519–525 (1997)

    Article  CAS  Google Scholar 

  13. Pigliucci, M. & Byrd, N. Genetics and evolution of phenotypic plasticity to nutrient stress in Arabidopsis: drift, constraints or selection? Biol. J. Linn. Soc. 64, 17–40 (1998)

    Google Scholar 

  14. Stratton, D. A. Reaction norm functions and QTL–environment interactions for flowering time in Arabidopsis thaliana. Heredity 81, 144–155 (1998)

    Article  Google Scholar 

  15. Dorn, L. A., Pyle, E. H. & Schmitt, J. Plasticity to light cues and resources in Arabidopsis thaliana: testing for adaptive value and costs. Evolution 54, 1982–1994 (2000)

    Article  CAS  Google Scholar 

  16. Milioni, D. & Hatzopoulos, P. Genomic organization of hsp90 gene family in Arabidopsis. Plant Mol. Biol. 35, 955–961 (1997)

    Article  CAS  Google Scholar 

  17. Krishna, P. & Gloor, G. The Hsp90 family of proteins in Arabidopsis thaliana. Cell Stress Chaperon. 6, 238–246 (2001)

    Article  CAS  Google Scholar 

  18. Roe, S. M. et al. Structural basis for inhibition of the Hsp90 molecular chaperone by the antitumor antibiotics radicicol and geldanamycin. J. Med. Chem. 42, 260–266 (1999)

    Article  CAS  Google Scholar 

  19. Dutta, R. & Inouye, M. GHKL, an emergent ATPase/kinase superfamily. Trends Biochem. Sci. 25, 24–28 (2000)

    Article  CAS  Google Scholar 

  20. Alonso-Blanco, C. et al. Development of an AFLP based linkage map of Ler, Col and Cvi Arabidopsis thaliana ecotypes and construction of a Ler/Cvi recombinant inbred line population. Plant J. 14, 259–271 (1998)

    Article  CAS  Google Scholar 

  21. Mayfield, J. A., Fiebig, A., Johnstone, S. E. & Preuss, D. Gene families from the Arabidopsis thaliana pollen coat proteome. Science 292, 2482–2485 (2001)

    Article  CAS  Google Scholar 

  22. Queitsch, C., Hong, S. W., Vierling, E. & Lindquist, S. Heat shock protein 101 plays a crucial role in thermotolerance in Arabidopsis. Plant Cell 12, 479–492 (2000)

    Article  CAS  Google Scholar 

  23. Donohue, K., Messiqua, D., Pyle, E. H., Heschel, M. S. & Schmitt, J. Evidence of adaptive divergence in plasticity: density- and site-dependent selection on shade-avoidance responses in Impatiens capensis. Evolution 54, 1956–1968 (2000)

    Article  CAS  Google Scholar 

  24. Ballare, C. L. Keeping up with the neighbours: phytochrome sensing and other signalling mechanisms. Trends Plant Sci. 4, 97–102 (1999)

    Article  CAS  Google Scholar 

  25. Kimura, M. Recent development of the neutral theory viewed from the Wrightian tradition of theoretical population genetics. Proc. Natl Acad. Sci. USA 88, 5969–5973 (1991)

    Article  CAS  ADS  Google Scholar 

  26. Ludwig, M. Z., Bergman, C., Patel, N. H. & Kreitman, M. Evidence for stabilizing selection in a eukaryotic enhancer element. Nature 403, 564–567 (2000)

    Article  CAS  ADS  Google Scholar 

  27. Hansen, T. F., Carter, A. J. & Chiu, C. H. Gene conversion may aid adaptive peak shifts. J. Theor. Biol. 207, 495–511 (2000)

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank H. Oakley, A. Evans and the University of Chicago greenhouse staff for technical help. We are especially grateful to J. Malamy, J. Greenberg, D. Preuss, J. Borevitz, J. Maloof and members of the Lindquist laboratory for advice and discussions, and to N. Patel for use of equipment and comments. We thank the ABRC for seeds. T.A.S. is a Howard Hughes Medical Institute pre-doctoral fellow. S.L. thanks the Howard Hughes Medical Institute and the National Institutes of Health for their support.

Author information

Author notes

  1. Susan Lindquist

    Present address: Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, Massachusetts, 02142, USA

Authors and Affiliations

  1. Department of Molecular Genetics and Cell Biology, Howard Hughes Medical Institute, University of Chicago, Chicago, Illinois, 60637, USA

    Christine Queitsch & Susan Lindquist

  2. Committee on Genetics, Howard Hughes Medical Institute, University of Chicago, Chicago, Illinois, 60637, USA

    Todd A. Sangster

Authors
  1. Christine Queitsch
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Todd A. Sangster
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Susan Lindquist
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Susan Lindquist.

Ethics declarations

Competing interests

The authors declare that they have no competing financial interests.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Queitsch, C., Sangster, T. & Lindquist, S. Hsp90 as a capacitor of phenotypic variation. Nature 417, 618–624 (2002). https://doi.org/10.1038/nature749

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature749

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Advanced 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