Wolf, J. B. | Search bioRxiv

bioRxiv2021

Runaway evolution from male-male competition

Wondrously elaborate weapons and displays that appear to be counter to ecological optima are widespread features of male contests for mates across the animal kingdom. To understand how such diverse traits evolve, here we develop a quantitative genetic model of sexual selection for a male signaling trait that mediates aggression in male-male contests and show that an honest indicator of aggression can generate selection on itself by altering the social environment. This can cause selection to accelerate as the trait is elaborated, leading to runaway evolution. Thus, an evolving source of selection provided by the social environment is the fundamental unifying feature of runaway sexual selection driven by either male-male competition or female mate choice. However, a key difference is that runaway driven by male-male competition requires signal honesty. Our model identifies simple conditions that provide clear, testable predictions for empirical studies using standard quantitative genetic methods.

evolutionary biology↗

bioRxiv2020

The C-terminus and Third Cytoplasmic Loop Cooperatively Activate Mouse Melanopsin Phototransduction

Melanopsin, an atypical vertebrate visual pigment, mediates non-image forming light responses including circadian photoentrainment and pupillary light reflexes, and contrast detection for image formation. Melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs), are characterized by sluggish activation and deactivation of their light responses. The molecular determinants of mouse melanopsins deactivation have been characterized (i.e. C-terminal phosphorylation and {beta}-arrestin binding), but a detailed analysis of melanopsins activation is lacking. We propose that an extended 3rd cytoplasmic loop is adjacent to the proximal C-terminal region of mouse melanopsin in the inactive conformation which is stabilized by ionic interaction of these two regions. This model is supported by site-directed spin labeling and electron paramagnetic resonance (EPR) spectroscopy of melanopsin, the results of which suggests a high degree of steric freedom at the 3rd cytoplasmic loop, which is increased upon C-terminus truncation, supporting the idea that these two regions are close in 3-dimensional space in wild-type melanopsin. To test for a functionally critical C-terminal conformation, calcium imaging of melanopsin mutants including a proximal C-terminus truncation (at residue 365) and proline mutation of this proximal region (H377P, L380P, Y382P) delayed melanopsins activation rate. Mutation of all potential phosphorylation sites, including a highly conserved tyrosine residue (Y382), into alanines also delayed the activation rate. A comparison of mouse melanopsin with armadillo melanopsin--which has substitutions of various potential phosphorylation sites and a substitution of the conserved tyrosine--indicates that substitution of these potential phosphorylation sites and the tyrosine residue result in dramatically slower activation kinetics, a finding that also supports the role of phosphorylation in signaling activation. We therefore propose that melanopsins C-terminus is proximal to intracellular loop 3 and C-terminal phosphorylation permits the ionic interaction between these two regions, thus forming a stable structural conformation that is critical for initiating G-protein signaling. STATEMENT OF SIGNIFICANCEMelanopsin is an important visual pigment in the mammalian retina that mediates non-image forming responses such as circadian photoentrainment and pupil constriction, and supports contrast detection for image formation. In this study, we detail two critical structural features of mouse melanopsin--its 3rd cytoplasmic loop and C-terminus--that are important in the activation of melanopsins light responses. Furthermore, we propose that these two regions directly participate in coupling mouse melanopsin to its G-protein. These findings contribute to further understanding of GPCR-G-protein coupling, and given recent findings suggesting flexibility of melanopsin signal transduction in the retina (possibly by coupling more than one G-protein type), these findings provide insight into the molecular basis of melanopsin function in the retina.

neuroscience↗