2018/10/25 by Gianni M. Castiglione, Belinda S. W. Chang · 1 voice · 1 citation
Biochemistry, Genetics and Molecular Biology · Neuroscience · Social Sciences · #Evolution and Genetic Dynamics #Evolutionary Game Theory and Cooperation #Neural dynamics and brain function
paper · doi:10.7554/elife.35957
openalex publication_date 2018/10/25 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/12
Trade-offs between protein stability and activity can restrict access to evolutionary trajectories, but widespread epistasis may facilitate indirect routes to adaptation. This may be enhanced by natural environmental variation, but in multicellular organisms this process is poorly understood. We investigated a paradoxical trajectory taken during the evolution of tetrapod dim-light vision, where in the rod visual pigment rhodopsin, E122 was fixed 350 million years ago, a residue associated with increased active-state (MII) stability but greatly diminished rod photosensitivity. Here, we demonstrate that high MII stability could have likely evolved without E122, but instead, selection appears to have entrenched E122 in tetrapods via epistatic interactions with nearby coevolving sites. In fishes by contrast, selection may have exploited these epistatic effects to explore alternative trajectories, but via indirect routes with low MII stability. Our results suggest that within tetrapods, E122 and high MII stability cannot be sacrificed—not even for improvements to rod photosensitivity.