Cross-species single-cell transcriptomic atlas of retinal photoreceptors reveals molecular signatures underlying color vision adaptation.

The retina exhibits conserved structural and functional features across species, yet the evolutionary mechanisms underlying color vision remain unclear. Here, we employ a single-cell prediction (scPred) model to construct a cross-species single-cell retinal atlas from 24 species. We identify conserved retinal cell types and expression patterns, with photoreceptor cells, especially rods, showing evolutionary shifts. Opsin expression and transcriptional programs in rods and cones display species-specific patterns. Cone subtypes exhibit distinct metabolic features, with fatty acid biosynthesis enriched in OPN1SW+ and OPN1MW+ cones and FOXO3 specifically linked to OPN1LW+ cones. Fluorescence in situ hybridization (FISH) and quantitative real-time PCR validate cone subtype-specific transcription factors and metabolic genes in representative species. This work provides a valuable resource for understanding the transcriptional and metabolic basis of color vision and guides the selection of model organisms for studying color-vision-related diseases.