An HSP90-regulated reduced-eye phenotype in Tribolium shows fitness benefits and thus provides evidence for evolutionary capacitance

Evolution relies on genetic variation as the raw material for adaptation. The release of cryptic genetic variation (CGV), which can be regulated by the evolutionary capacitor heat shock protein 90 (HSP90), may thus be important for rapid adaptation. However, the fitness benefits of HSP90-regulated phenotypes are still under debate. Here, we show in the important model insect Tribolium castaneum that HSP90 impairment by two independent methods, RNA interference and chemical inhibition, revealed the same reduced-eye phenotype, which was stably inherited without further HSP90 inhibition. The penetrance and fitness of this trait increased under ambient light stress. This is the first demonstration that a phenotype released through HSP90 inhibition can be adaptive.

Protein evolution speed depends on its stability and abundance and on chaperone concentrations

Proteins evolve at different rates. What drives the speed of protein sequence changes? Two main factors are a protein’s folding stability and aggregation propensity. By combining the hydrophobic–polar (HP) model with the Zwanzig–Szabo–Bagchi rate theory, we find that: (i) Adaptation is strongly accelerated by selection pressure, explaining the broad variation from days to thousands of years over which organisms adapt to new environments. (ii) The proteins that adapt fastest are those that are not very stably folded, because their fitness landscapes are steepest. And because heating destabilizes folded proteins, we predict that cells should adapt faster when put into warmer rather than cooler environments. (iii) Increasing protein abundance slows down evolution (the substitution rate of the sequence) because a typical protein is not perfectly fit, so increasing its number of copies reduces the cell’s fitness. (iv) However, chaperones can mitigate this abundance effect and accelerate evolution (also called evolutionary capacitance) by effectively enhancing protein stability. This model explains key observations about protein evolution rates.

Evolutionary capacitance emerges spontaneously during adaptation to environmental changes

ABSTRACTAll biological populations are to a greater or lesser degree evolvable, but the forces that shape evolvability, especially the evolution of evolvability as an adaptive response to a changing environment, have been a source of controversy. One source of enhanced evolvability is the benign status of “cryptic sequences” typically expressed at low levels due to molecular errors, but with the potential to be expressed more fully following mutational co-option. A genome enriched for benign cryptic sequences has a more benign mutational neighborhood, via the possibility of co-option, and thus enhanced evolvability. Whether selection for evolvability itself can be the cause of a more benign mutational neighborhood remains an open question. Here, we show that environmental change can cause the evolution of increased evolvability, despite our use of a strong-selection weak mutation regime that precludes, by design, the adaptive evolution of evolvability. Instead, enhanced evolvability arises as a byproduct of environmental change via a novel mechanism that we call “emergent evolutionary capacitance”. When the environment changes, increased molecular error rates evolve as a strategy to rapidly change phenotypes, with the side effect of purging deleterious cryptic sequences and enhancing the mutational neighborhood for future adaptation. The behavior is strikingly similar to that seen in a model system for capacitance, the yeast prion [PSI+].