Serpin-driven green camouflage and NIR fluorescence in frogs.

Biliverdin is one of the few endogenous green pigments in animals, yet its use in camouflage and fluorescence is limited by rapid degradation or excretion. Multiple arboreal frogs have overcome this constraint by evolving biliverdin-binding serpins (BBSs)-proteins that stabilize biliverdin. Here, we show that BBSs have convergently evolved high-affinity biliverdin binding comparable to hormone-receptor interactions and tune biliverdin's spectral properties to produce leaf-like green coloration. We further show that BBSs from independent lineages exhibit distinct spectral properties, including near-infrared fluorescence. Unlike most animal serpins, which are rapidly cleared following proteolytic cleavage, a glassfrog's BBS is naturally cleaved while retaining full biliverdin-binding affinity, revealing an unusual decoupling between serpin proteolysis and ligand binding. Using photoacoustic tomography, we map the distribution of BBS throughout the body, uncovering a mechanism of protein-based camouflage. These findings provide insights into serpin evolution and protein-based coloration while establishing a foundation for amphibian-inspired near-infrared molecular probe design.