Evolutionary Constraint on Visual and Nonvisual Mammalian Opsins

Abstract

Animals have evolved light-sensitive G protein–coupled receptors, known as opsins, to detect coherent and ambient light for visual and nonvisual functions. These opsins have evolved to satisfy the particular lighting niches of the organisms that express them. While many unique patterns of evolution have been identified in mammals for rod and cone opsins, far less is known about the atypical mammalian opsins. Using genomic data from over 400 mammalian species from 22 orders, unique patterns of evolution for each mammalian opsins were identified, including photoisomerases, RGR-opsin (RGR) and peropsin (RRH), as well as atypical opsins, encephalopsin (OPN3), melanopsin (OPN4), and neuropsin (OPN5). The results demonstrate that OPN5 and rhodopsin show extreme conservation across all mammalian lineages. The cone opsins, SWS1 and LWS, and the nonvisual opsins, OPN3 and RRH, demonstrate a moderate degree of sequence conservation relative to other opsins, with some instances of lineage-specific gene loss. Finally, the photoisomerase, RGR, and the best-studied atypical opsin, OPN4, have high sequence diversity within mammals. These conservation patterns are maintained in human populations. Importantly, all mammalian opsins retain key amino acid residues important for conjugation to retinal-based chromophores, permitting light sensitivity. These patterns of evolution are discussed along with known functions of each atypical opsin, such as in circadian or metabolic physiology, to provide insight into the observed patterns of evolutionary constraint.

Expression of Retinal G Protein-Coupled Receptor, a Member of the Opsin Family, in Human Skin Cells and Its Mediation of the Cellular Functions of Keratinocytes

“…Although the RGR is poorly conserved, it sustains the responsiveness of photoreceptor cells ( Upton et al, 2021 ). The mutant RGR causes many diseases, such as dominantly inherited peripapillary choroidal atrophy (c.824dupG, p. I276Nfs*77) ( Upton et al, 2021 ).…”

“…Although the RGR is poorly conserved, it sustains the responsiveness of photoreceptor cells ( Upton et al, 2021 ). The mutant RGR causes many diseases, such as dominantly inherited peripapillary choroidal atrophy (c.824dupG, p. I276Nfs*77) ( Upton et al, 2021 ). Abnormal RGR proteins, including RGR-d (an exon-skipping splice variant), strongly inhibit cell growth in vitro ( Bao et al, 2021 ).…”

Violet light modulates the central nervous system to regulate memory and mood

“…OPN5 is the most conserved non-visual opsin in mammals compared to OPN3 and OPN4, and is found in frogs, birds, and mammals 27,28 . Although Laurasiatheria, Afrotheria, Xenartheria, Euarchontoglire, and other mammals have different opsins related to visual information depending on their living environment, the fact that all these mammals have OPN4 and OPN5 suggests that OPN4 and OPN5 play a crucial role in controlling tissue functions in response to light environment.…”

Recognition of Melanocytes in Immuno-Neuroendocrinology and Circadian Rhythms: Beyond the Conventional Melanin Synthesis

“…Numerous studies in the past two decades have strongly suggested that opsins in the retina play a special role in the photoentrainment of mammalian circadian rhythms [106,107,119]. In particular, the opsin family evolved prior to the evolution of image-forming visual systems, suggesting that the original role of opsins was nonvisual, including checking time-of-day information based on photoperiod, intensity, and wavelength of light [144].…”

“…As mentioned, reptiles utilize the parietal eye as a photoreceptor, which disappeared during evolution [128,141,150]. Consequently, it has been proposed that a photosensitive system may have evolved in mammal skin to compensate for parietal eye loss [127,144].…”