Signatures of an evolutionary capacitor from a high-resolution Luria-Delbruck assay

Pre-existing genetic diversity drives adaptation, but the factors that determine standing genetic variation in a population remain poorly understood. The chaperone Hsp90 has been proposed to act as an `evolutionary capacitor': buffering the deleterious impact of new mutations and allowing them to persist in a population. Yet, the scope and magnitude of such buffering remains unknown. Here, we generalise the assay of Luria and Delbruck to probe Hsp90's role in the acquisition of antibiotic resistance by \textit{S. cerevisiae}. Resistance mutations buffered by Hsp90 can arise early and grow to a `jackpot' of mutants, with a corresponding long-tail in the Luria-Delbruck distribution. In contrast, when Hsp90 is compromised, early mutations are selected against and the tail of distribution is truncated. We complement our statistical results with a targeted mutation-accumulation assay. Overall, our results suggest how cellular processes can dictate the ebb and flow of genetic diversity in a population.