Functional trade-offs and environmental variation shaped ancient trajectories in the evolution of dim-light vision

Abstract

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.

Recreated Ancestral Opsin Associated with Marine to Freshwater Croaker Invasion Reveals Kinetic and Spectral Adaptation

“…( B ) Retinal release rate for bovine rhodopsin and bovine rhodopsin with substitutions matching the marine and freshwater croaker sequences at site 119, 122, 124, and 261. Marine substitutions previously published in Castiglione and Chang (2018) . ( C ) Bar chart comparing retinal release rate half-life for each pigment.…”

“…2010 ), and recovery phase of the light-activated receptor ( Hauser et al. 2017 ; Castiglione and Chang 2018 ; Gutierrez et al. 2018 ; Liu et al.…”

The ancient cardioprotective mechanisms of ACE2 bestow SARS-CoV-2 with a wide host range

“…Why did these substitutions serendipitously blocking SARS-CoV-2 binding only evolve in some rodent species? The compensatory interactions inherent to intramolecular epistasis can both open and close evolutionary trajectories depending on how accessible favorable mutational combinations are within evolutionary space (31,(52)(53)(54). In humans and dogs, this trajectory appears to have been closed by the presence of deep valleys containing detrimental intermediates with compromised ACE2 function (Fig.…”

“…Given the importance of ACE2 enzymatic processing of Ang II to Ang-(1-7) in protection against pathogenic features of multiple cardiovascular and kidney diseases (37,41,42), it is possible that that the extant mutational combinations observed in nature (e.g. human, bat, dog, mouse, pangolin) may all represent alternative sequence 'solutions' (34,52) each uniquely required for an animal's physiology, thereby representing fitness 'peaks' in the sequence landscape (28,31,34,53,(63)(64)(65). Species variation in ACE2 hydrolysis rates we observed may reflect variation in renin activity levels, which are a major factor in determining circulating Ang-II levels in humans (39,66,67).…”

To see or not to see: molecular evolution of the rhodopsin visual pigment in neotropical electric fishes

“…We found positively selected substitutions in the lineage leading to gymnotiforms in helices that are known to undergo the largest molecular movements upon rhodopsin photoactivation [33], and where substitutions have been shown in mutagenesis studies to affect the kinetics of chromophore release by rhodopsin [43 -45]. Substitutions that affect rhodopsin kinetics are known to have evolved convergently in distantly related species inhabiting dim-light environments [46,47], including other fishes inhabiting the same rivers of the Amazon basin [37]. Interestingly, mutagenesis studies in bovine rhodopsin have also shown that the F220C substitution experimentally decreases the rate of retinal release [35].…”