Evolutionary Constraint on Visual and Nonvisual Mammalian Opsins

J Biol Rhythms. 2021 Apr;36(2):109-126. doi: 10.1177/0748730421999870. Epub 2021 Mar 25.


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.

Keywords: RGR-opsin; atypical; encephalopsin; melanopsin; neuropsin; peropsin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Circadian Rhythm / radiation effects
  • Conserved Sequence
  • Evolution, Molecular*
  • Humans
  • Mammals / metabolism*
  • Mice
  • Opsins / chemistry
  • Opsins / genetics
  • Opsins / metabolism*
  • Opsins / radiation effects*
  • Receptors, G-Protein-Coupled / chemistry
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism
  • Receptors, G-Protein-Coupled / radiation effects
  • Retina / metabolism
  • Retina / radiation effects
  • Rhodopsin / chemistry
  • Rhodopsin / genetics
  • Rhodopsin / metabolism
  • Rhodopsin / radiation effects


  • Opsins
  • Receptors, G-Protein-Coupled
  • Rhodopsin