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Hsp90 prevents phenotypic variation by suppressing the mutagenic activity of transposons


The canalization concept1 describes the resistance of a developmental process to phenotypic variation, regardless of genetic and environmental perturbations, owing to the existence of buffering mechanisms. Severe perturbations, which overcome such buffering mechanisms, produce altered phenotypes that can be heritable and can themselves be canalized by a genetic assimilation process. An important implication of this concept is that the buffering mechanism could be genetically controlled. Recent studies on Hsp90, a protein involved in several cellular processes and development pathways2,3,4,5, indicate that it is a possible molecular mechanism for canalization and genetic assimilation. In both flies and plants, mutations in the Hsp90-encoding gene induce a wide range of phenotypic abnormalities, which have been interpreted as an increased sensitivity of different developmental pathways to hidden genetic variability6,7. Thus, Hsp90 chaperone machinery may be an evolutionarily conserved buffering mechanism of phenotypic variance, which provides the genetic material for natural selection. Here we offer an additional, perhaps alternative, explanation for proposals of a concrete mechanism underlying canalization. We show that, in Drosophila, functional alterations of Hsp90 affect the Piwi-interacting RNA (piRNA; a class of germ-line-specific small RNAs) silencing mechanism leading to transposon activation and the induction of morphological mutants. This indicates that Hsp90 mutations can generate new variation by transposon-mediated ‘canonical’ mutagenesis.

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Figure 1: hsp83 mutations activate Stellate sequences and affect crystal and transposon piRNA production.
Figure 2: hsp83 mutations and geldanamycin activate transposon transcription.
Figure 3: Southern blot analysis of DNA from single flies with different genotypes.
Figure 4: Analysis of the morphological mutant identified among hsp83 scratch homozygous flies.

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This study was supported by a grant from the Ministero dell’Universitá e della Ricerca (MIUR) project: RNAi, heterochromatin and epigenetic control of gene expression and chromosome behaviour. V.S. was supported by a grant provided by MIUR for the same project.

Author Contributions V.S., L.P., P.T., L.F., R.D. and G.P. performed research; S.P. and M.P.B. designed research; S.P. and M.P.B. analysed data and wrote the paper; all authors discussed the results and commented on the manuscript.

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Correspondence to Maria P. Bozzetti.

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Specchia, V., Piacentini, L., Tritto, P. et al. Hsp90 prevents phenotypic variation by suppressing the mutagenic activity of transposons. Nature 463, 662–665 (2010).

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