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Evidence for an epigenetic mechanism by which Hsp90 acts as a capacitor for morphological evolution

Abstract

Morphological alterations have been shown to occur in Drosophila melanogaster when function of Hsp90 (heat shock 90-kDa protein 1α, encoded by Hsp83) is compromised during development1. Genetic selection maintains the altered phenotypes in subsequent generations1. Recent experiments have shown, however, that phenotypic variation still occurs in nearly isogenic recombinant inbred strains of Arabidopsis thaliana2. Using a sensitized isogenic D. melanogaster strain, iso-KrIf-1, we confirm this finding and present evidence supporting an epigenetic mechanism for Hsp90's capacitor function, whereby reduced activity of Hsp90 induces a heritably altered chromatin state. The altered chromatin state is evidenced by ectopic expression of the morphogen wingless in eye imaginal discs and a corresponding abnormal eye phenotype, both of which are epigenetically heritable in subsequent generations, even when function of Hsp90 is restored. Mutations in nine different genes of the trithorax group that encode chromatin-remodeling proteins also induce the abnormal phenotype. These findings suggest that Hsp90 acts as a capacitor for morphological evolution through epigenetic and genetic mechanisms.

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Figure 1: Maternal loss of one copy of Hsp83 can generate ectopic outgrowth in D. melanogaster eyes.
Figure 2: vtd3 and geldanamycin selection experiments showed higher frequency of outgrowth in later generations.
Figure 3: Ectopic expression of wg02657-lacZ was induced by Hsp83 mutations.
Figure 4: HDAC inhibitors lowered the frequency of ectopic outgrowth in flies.

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References

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

    Article  CAS  Google Scholar 

  2. Queitsch, C., Sangster, T.A. & Lindquist, S. Hsp90 as a capacitor of phenotypic variation. Nature 417, 618–624 (2002).

    Article  CAS  Google Scholar 

  3. Jackle, H. et al. Molecular analysis of Kruppel, a segmentation gene of Drosophila melanogaster. Cold Spring Harb. Symp. Quant. Biol. 50, 465–473 (1985).

    Article  CAS  Google Scholar 

  4. Carrera, P. et al. A modifier screen in the eye reveals control genes for Kruppel activity in the Drosophila embryo. Proc. Natl. Acad. Sci. USA 95, 10779–10784 (1998).

    Article  CAS  Google Scholar 

  5. Abrell, S., Carrera, P. & Jackle, H. A modifier screen of ectopic Kruppel activity identifies autosomal Drosophila chromosomal sites and genes required for normal eye development. Chromosoma 109, 334–342 (2000).

    Article  CAS  Google Scholar 

  6. Kennison, J.A. & Tamkun, J.W. Dosage-dependent modifiers of polycomb and antennapedia mutations in Drosophila. Proc. Natl. Acad. Sci. USA 85, 8136–8140 (1988).

    Article  CAS  Google Scholar 

  7. Paro, R., Strutt, H. & Cavalli, G. Heritable chromatin states induced by the Polycomb and trithorax group genes. Novartis Found. Symp. 214, 51–61 (1998).

    CAS  PubMed  Google Scholar 

  8. Dickson, B.J., van der Straten, A., Dominguez, M. & Hafen, E. Mutations modulating Raf signaling in Drosophila eye development. Genetics 142, 163–171 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Mollaaghababa, R. et al. Mutations in Drosophila heat shock cognate 4 are enhancers of Polycomb. Proc. Natl. Acad. Sci. USA 98, 3958–3963 (2001).

    Article  CAS  Google Scholar 

  10. Lecuit, T. & Cohen, S.M. Proximal–distal axis formation in the Drosophila leg. Nature 388, 139–145 (1997).

    Article  CAS  Google Scholar 

  11. Gibson, M., Lehman, D. & Schubiger, G. Lumenal transmission of decapentaplegic in Drosophila imaginal discs. Dev. Cell 3, 451 (2002).

    Article  CAS  Google Scholar 

  12. Lecuit, T. & Cohen, S.M. Dpp receptor levels contribute to shaping the Dpp morphogen gradient in the Drosophila wing imaginal disc. Development 125, 4901–4907 (1998).

    CAS  PubMed  Google Scholar 

  13. Steffan, J.S. et al. Histone deacetylase inhibitors arrest polyglutamine-dependent neurodegeneration in Drosophila. Nature 413, 739–743 (2001).

    Article  CAS  Google Scholar 

  14. Kang, H.L., Benzer, S. & Min, K.T. Life extension in Drosophila by feeding a drug. Proc. Natl. Acad. Sci. USA 99, 838–843 (2002).

    Article  CAS  Google Scholar 

  15. Adams, M.D. et al. The genome sequence of Drosophila melanogaster. Science 287, 2185–2195 (2000).

    Article  Google Scholar 

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

    Article  Google Scholar 

  17. Waddington, C.H. Genetic assimilation of an acquired character. Evolution 7, 118–126 (1953).

    Article  Google Scholar 

  18. Kohler, C. & Grossniklaus, U. Epigenetics: the flowers that come in from the cold. Curr. Biol. 12, R129–R131 (2002).

    Article  CAS  Google Scholar 

  19. Bender, J. Plant epigenetics. Curr. Biol. 12, R412–R414 (2002).

    Article  CAS  Google Scholar 

  20. Gould, S.J. & Eldredge, N. Punctuated equilibrium comes of age. Nature 366, 223–227 (1993).

    Article  CAS  Google Scholar 

  21. Goldstein, L.S.B. Drosophila melanogaster: Practical Uses in Cell and Molecular Biology (Academic Press, San Diego, California, 1994).

    Google Scholar 

  22. Ashburner, M. Drosophila: A Laboratory Handbook (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, 1989).

    Google Scholar 

Download references

Acknowledgements

We thank J. Kennison for providing fly stocks, G. Schubiger for recognizing that the ectopic outgrowths had triplicate vibrissae, T. Townes for suggesting the trichostatin A and sodium butyrate experiments and J. Horabin, S. Wilson and M. Bertram for reviewing the manuscript. This work was supported by Basil O'Connor Starter Scholar Research Awards to X.L. and D.M.R., a grant from the American Cancer Society to X.L. and grants from the US National Institutes of Health to X.L. and D.M.R.

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Correspondence to Douglas M. Ruden.

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Sollars, V., Lu, X., Xiao, L. et al. Evidence for an epigenetic mechanism by which Hsp90 acts as a capacitor for morphological evolution. Nat Genet 33, 70–74 (2003). https://doi.org/10.1038/ng1067

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