PNAS has just published our paper, “Pervasive contingency and entrenchment in a billion years of Hsp90 evolution.”  It’s the product of a great collaboration with Dan Bolon’s lab, and our graduate student Tyler Starr is a co-first author. Here are links to the paper on the PNAS website and to the unrestricted PDF.
Quick summary:  We precisely quantified the fitness effects, in both present-day and reconstructed ancestral backgrounds, of every ancestral and derived state that occurred along Hsp90’s billion-year evolutionary trajectory from a deep eukaryotic ancestor to present-day S. cerevisiae. We found that the vast majority of historical substitutions were contingent on prior permissive mutations, subsequently entrenched by restrictive mutations, or both. This implies that epistasis continually opens and closes windows of mutational opportunity: the path that evolution ends up following reflects not only selection for optimal function but also the transient internal constraints imposed on the protein by its own fleeting sequence states.