biostudies-literatureMcDowell RJEuropean Research Councilmsaf158https://www.ebi.ac.uk/biostudies/studies/S-EPMC12461567biostudies-literatureUnknown42(9)Melanopsin is a light-sensitive G-protein coupled receptor responsible for essential visual and non-visual light-mediated behaviors in mammals. Human melanopsin shows maximal sensitivity (λmax) in the blue region of the spectrum (∼480 nm), and available evidence suggests that this spectral sensitivity may be retained across mammals. However, melanopsin spectral sensitivity has been defined for only a small number of species, and the molecular mechanisms determining this property remain poorly understood. Here, we use heterologous action spectroscopy to determine the spectral sensitivity of melanopsins from 8 mammalian species, selected to cover diversity in retinal physiology, lighting niche, and evolutionary distance, and of engineered mutants of mouse melanopsin designed to explore mechaMolecular biology and evolutionSpectral Tuning in Mammalian Melanopsins.PMC12461567951644951644-SOLLucas RJNotash SMcDowell RJGatt MJfalseSpectral Tuning in Mammalian Melanopsins.Melanopsin is a light-sensitive G-protein coupled receptor responsible for essential visual and non-visual light-mediated behaviors in mammals. Human melanopsin shows maximal sensitivity (λmax) in the blue region of the spectrum (∼480 nm), and available evidence suggests that this spectral sensitivity may be retained across mammals. However, melanopsin spectral sensitivity has been defined for only a small number of species, and the molecular mechanisms determining this property remain poorly understood. Here, we use heterologous action spectroscopy to determine the spectral sensitivity of melanopsins from 8 mammalian species, selected to cover diversity in retinal physiology, lighting niche, and evolutionary distance, and of engineered mutants of mouse melanopsin designed to explore mecha2025-01-01T00:00:00Z2025 Sep2026-05-01T03:22:29.399Z2026-05-01T03:11:08.768ZS-EPMC124615674099596710.1093/molbev/msaf158