Like a magician's cloak, heat shock protein 90 (Hsp90) hides the molecular variation contained within Drosophila and Arabidopsis populations — it is only when the masking effect of Hsp90 is lifted that a range of underlying morphologies appear. Favourable phenotypes revealed by the absence of Hsp90 activity can be fixed in the population and, therefore, persist even when Hsp90 function is restored. As with every conjuring trick, the question arises: how is it done? Fixation was thought to depend on the selection of pre-existing genetic variation in the population. Now, Sollars and colleagues report that, in Drosophila, phenotype fixation can also be caused by epigenetic alterations.

In their studies, the authors concentrated on the ectopic bristles seen in the eyes of flies in which Hsp90 function had been reduced through mutation or pharmacological inhibition. Offspring from flies fed an Hsp90-inhibiting drug were bred and selected for the eye bristle phenotype, for 13 generations, in the absence of the drug. The penetrance of the phenotype increased in response to selection and remained even when Hsp90 function was restored. However, as the strain of flies used in the experiment was nearly isogenic, genetic variation was unlikely to account for the fixation of the ectopic eye-bristle phenotype, as was previously thought. Instead, it was more likely that epigenetic changes affecting chromatin structure had occurred. In support of this idea, when flies from the F6 generation were treated with a histone deacetylase inhibitor — resulting in an increase in histone acetylation — the percentage of individuals showing ectopic eye bristles decreased significantly.

The authors also identified a further link between chromatin structure and ectopic eye bristles. A similar bristle phenotype to that seen in flies with compromised Hsp90 function was found in mutants of nine different trithorax group (trx) genes, which exhibit hypoacetylation. Once again, the phenotype was reduced by histone deacetylase inhibitor treatment. Selection studies on the most severe trx mutant showed that, although the mutation is required initially in the mother to generate the ectopic eye bristles, after selection it is not required to maintain the phenotype. It seems, therefore, that trx mutations induce ectopic outgrowths by altering chromatin structure in the egg and then an unknown epigenetic mechanism results in their fixation. This indicates that Hsp90 removal might induce epigenetic changes, possibly through an interaction with Trx proteins.

This study indicates that epigenetic changes might lead to the fixation of phenotypes that are normally buffered by Hsp90 and that are exposed by, for example, environmental stress. This mechanism for evolutionary change has important implications. First, evolution might proceed more rapidly when fixation occurs by epigenetic mechanisms. Second, an epigenetically determined phenotype is likely to be less stable than one fixed through genetic changes, and so might be reversed more easily.