Modularity and intrinsic evolvability of Hsp90-buffered change

Abstract

Hsp90 controls dramatic phenotypic transitions in a wide array of morphological features of many organisms. The genetic-background dependence of specific abnormalities and their response to laboratory selection suggested Hsp90 could be an 'evolutionary capacitor', allowing developmental variation to accumulate as neutral alleles under normal conditions and manifest selectable morphological differences during environmental stress. The relevance of Hsp90-buffered variation for evolution has been most often challenged by the idea that large morphological changes controlled by Hsp90 are unconditionally deleterious. To address this issue, we tested an Hsp90-buffered abnormality in Drosophila for unselected pleiotropic effects and correlated fitness costs. Up to 120-fold differences in penetrance among six highly related selection lines, started from an initially small number of flies and rapidly selected for and against a deformed eye trait (dfe), did not translate into measurable differences in any of several tests of viability, lifespan or competitive fitness. Nor were 17 dfe Quantitative Trait Loci (QTL) associated with fitness effects in over 1,400 recombinant lines. Our ability to detect measurable effects of inbreeding, media environment and the white mutation in the selection line backgrounds independent of dfe penetrance suggests that, within the limitations of laboratory tests of fitness, this large morphological change controlled by Hsp90 was selectable independent of strong, correlated and unconditionally deleterious effects--abundant, polygenic variation hidden by Hsp90 allows potentially deleterious alleles to be readily replaced during selection by less deleterious alleles with similar phenotypic effects. Hsp90 links environmental stress with the expression of developmental variation controlling unprecedented morphological plasticity. As outlined here and in the companion paper of this issue, the complex genetic architecture of Hsp90-buffered variation supports a remarkable modularity of Hsp90 effects on quantitative and qualitative phenotypes, consistent with the 'Hsp90 capacitor hypothesis' and standard quantitative genetic models of threshold traits.

Figure 1. Representative tests of penetrance, absolute and relative fitness.

High (red) and low (blue) lines, genetically differentiated for dfe penetrance were not differentiated by tests of viability and fitness. Controls (grey) were either Canton-S (CS) flies tested at the same time or published values for wild-type flies (WT; [21]). Experiments showing the most extreme between line differences are displayed. Error bars indicate the standard errors of the mean. A. Penetrance of eye deformity in dfe lines and CS flies reared at 25°C. B. Hatch rate of timed embryo collections measured at 36 hours post egg-laying. C. Egg-to-adult survival measured as the number of adult flies emerging versus eggs laid. D. Fractional survivial of dfe progeny in competition with CS flies co-cultured at high density. E. Lifetime female production of eggs (wild-type values; [21]) or viable adult offspring (high and low line dfe females).

Figure 2. Survival curves for high and low dfe lines.

For simplicity, male and female values were grouped and equal numbers of each sex within each line are represented. Multiple independent comparisons failed to detect longevity differences between high and low lines (Table 1).

Figure 3. Regression of early fecundity and viability onto penetrance in 1,432 recombinant isogenic lines.

If genes for dfe had effects on viability and survival, a negative relationship would be expected, however penetrance was positively correlated with fitness in recombinant lines from HE1 and HE3.