The allostery principle supports the symbolic character of signaling circuits: gene regulation provides a form of intelligence to living systems.

Biology faces the challenge of articulating general principles capable of organizing and conceptually integrating its immense diversity. Since the operon and allosteric models of the 1960s, the regulatory landscape has expanded dramatically. Building on classical allosteric regulation, I propose the allostery principle, which stipulates that the combinatorial diversity in gene regulation arises from the use of two independent sites that can link any two molecular species within a signaling process, independent of specific mechanistic implementations. I provide empirical evidence that the allostery principle has been implemented repeatedly in six distinct molecular platforms during evolution, generating symbolic genetic explosions that expanded the combinatorial diversity of gene regulation. Four involve bacterial genetic platforms, including protein regulators, promoters, and small RNAs. Two involve eukaryotic platforms: intrinsically disordered proteins coupled with alternative splicing, and the extensive complex multicellular eukaryotic regulation mediated by non-coding RNAs. Remarkably, the central Merge operation within the minimalist generative model of the human language faculty-another symbolic explosion in evolution-conceptually satisfies the allostery principle. I further propose that regulatory signaling fluxes constitute a theory physically instantiated within organisms' architecture, functioning as a compressed representation with a strong explanatory power of its capabilities. The concept of missing regulatability provides the required falsifiability for this theoretical construct. Gene regulation implements physiological capabilities whose global significance derives from alignment with universally encoded biological ends-survival, reproduction, development, and differentiation. A system that responds to the environment making the adequate changes to achieve its final ends is showing the ability to instantiate intelligent actions. Therefore, gene regulation provides a form of intelligence to biological systems. This definition matches with intelligence in physical symbol systems formalized early in artificial intelligence. Adequate interpretations of these results and their implications are discussed. "It is the union of passionate interest in the detailed facts with equal devotion to abstract generalization which forms the novelty in our present society" (Whitehead 1925).