Selection Transforms the Landscape of Genetic Variation Interacting with Hsp90

Area of Science:

• Molecular Biology
• Evolutionary Biology
• Genetics

Background:

• The protein-folding chaperone Hsp90 is hypothesized to buffer phenotypic effects of mutations, influencing disease models, quantitative genetics, and evolutionary theory.
• However, Hsp90 can also potentiate rapid phenotypic changes, contradicting its buffering role.

Purpose of the Study:

• To quantify the buffering or potentiating effects of Hsp90 on genetic variation.
• To investigate Hsp90's impact on single-cell morphological features in budding yeast under varying selection pressures.

Main Methods:

• Quantification of Hsp90's effect on genetic variation in budding yeast.
• Analysis of single-cell morphological features.
• Distinguishing effects on standing genetic variation versus spontaneous mutations/recombinations.

Main Results:

• Hsp90 buffers the effects of standing genetic variation in natural populations, consistent with previous reports.
• Hsp90 potentiates, rather than buffers, the effects of spontaneous mutations and genetic variation under reduced selection pressure.

Conclusions:

• Hsp90 does not inherently increase robustness to genetic perturbations.
• Natural selection favors alleles buffered by Hsp90, leading to an overestimation of Hsp90's buffering capacity.