Quantitative genetic analysis of HSP90-buffered variation

Manipulation of the molecular chaperone HSP90 results in the expression of altered phenotypes at low penetrance in natural populations. Previous work has shown that these phenotypes are due to the exposure of normally cryptic genetic variation. Exposure of such "buffered" genetic polymorphisms may also be accomplished by environmental modulation. Should such polymorphisms be widespread, natural selection may be more effective at producing phenotypic change in suboptimal environments. Key factors influencing this hypothesis are the frequency and nature of HSP90-buffered polymorphisms in natural populations. Bounds on these quantities are unknown.;I employed two complementary approaches to elucidate the frequency and identity of HSP90-buffered polymorphisms in the model plant Arabidopsis thaliana. First, I used pharmacological inhibition to examine the effect of HSP90 modulation on the genetic basis of natural differences in the developmental responses of hypocotyl and root elongation in the dark. Second, I designed A. thaliana with constitutively reduced HSP90 levels and used them to assess HSP90-buffered polymorphisms affecting a variety of life-history traits.;My results allow several conclusions to be drawn. First, HSP90-dependent alleles are amenable to genetic mapping techniques and are unlikely to be purely epigenetic. Second, continuous, environmentally responsive traits can be affected by HSP90-dependent polymorphisms, contrary to suggestions that such alleles only affect highly canalized traits. Third, HSP90-dependent alleles are observed at such frequency in populations of A. thaliana that, when comparing two different natural accessions, nearly every trait may be expected to be affected by HSP90-dependent variation. Fourth, the effects of these polymorphisms are not immediately deleterious and could reasonably be advantageous under certain conditions. Fifth, HSP90 modulation can both reveal and conceal the phenotypic effects of natural variation. Sixth, HSP90 activity increases developmental stability; some of this effect depends on underlying genetic differences. Finally, the phenotypic effect of revealed polymorphisms can outweigh that of decreased developmental stability; the frequency of such polymorphisms could be increased by selection. Thus, I conclude that the raw potential for evolutionary change may be highly dependent on the genetic and environmental context, with HSP90 in a central position linking the environment to the translation of genotype to phenotype.