Biophysical resetting of specialization drives evolutionary diversification of a metabolic network

Abstract

Organisms must integrate external inputs whose availability they do not control into internal functions that require precision. Birds exemplify this challenge: they cannot synthesize carotenoids, yet closely integrate diet-derived carotenoids into vision, pigmentation and yolk provisioning, raising the question of how unpredictability of external supply coevolves with precision of internal use. Here we analyze 32 core carotenogenesis proteins across 172 bird species and show that the resolution is a biophysical bow-tie: ordered, self-attracting complexes of absorption and enzymatic conversion proteins are linked by a hub of disordered, phase-separating and self-avoiding carriers that consistently resets the propagation of specialization. Across species, the specialization-resetting properties of these carriers and not the changes in conserved absorption or enzymatic complexes drive metabolic network diversification by inducing metabolic branching rather than by accumulating dietary carotenoid-specific paths. By decoupling the upstream origin of inputs from their downstream routing, this biophysical bow-tie architecture explains three defining features of avian carotenogenesis: physiological sensitivity, openness to novel inputs, and the internalization of control required for precise internal functions. Non-specific carriers thus produce specific outcomes, sustaining the connectivity and remarkable diversification of a metabolic network built entirely on an unpredictable external resource.