Article | Published:

Hsp90 as a capacitor of phenotypic variation

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.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1

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

  2. 2

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

  3. 3

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

  4. 4

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

  5. 5

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

  6. 6

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

  7. 7

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

  8. 8

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

  9. 9

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

  10. 10

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

  11. 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)

  12. 12

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

  13. 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)

  14. 14

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

  15. 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)

  16. 16

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

  17. 17

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

  18. 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)

  19. 19

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

  20. 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)

  21. 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)

  22. 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)

  23. 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)

  24. 24

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

  25. 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)

  26. 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)

  27. 27

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

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

Correspondence to Susan Lindquist.

Ethics declarations

Competing interests

The authors declare that they have no competing financial interests.

Supplementary information

Supplementary figure S1 and analysis (DOC 211 kb)

Rights and permissions

Reprints and Permissions

About this article

Further reading

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.

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.