The Cost Is Not the Constraint: A Drift-Barrier Analysis of GPCR-Class Signalling in Unicellular Systems

Abstract

A widely held intuition in evolutionary cell biology holds that complex signalling machinery is excluded from unicellular organisms by energetic expense. This paper tests that intuition on a well-posed case and finds it false. Explicit bioenergetic accounting places a complete G-protein-coupled receptor (GPCR) signalling unit (~2700 residues) at approximately 0.22% of the cellular energy budget per generation at physiological copy number, against 0.04% for a bacterial two-component sensor — a relative burden of ρ = 5.40. Monte Carlo exploration of the drift-barrier fixation condition (N = 200,000 draws, fixed seed) finds such systems fixable across 55.7% of the sampled parameter space, against 74.0% for the two-component sensor: a ratio of admissible volumes of only 1.33×. Reaching a prohibitive burden would require 4.63 × 10⁵ receptor-system copies per cell, an order of magnitude above any reported figure. The cost-magnitude argument is therefore withdrawn explicitly, placing this case on the Lynch & Marinov side of an active dispute with Lane & Martin over whether energetic burden constrains cellular complexity. The binding constraint is structural rather than budgetary. The standing cost is incurred unconditionally, from the moment the system is expressed and independently of signalling traffic; the benefit is realised only on the condition that downstream coupling to a fitness-relevant output exists. Cost enters the selection coefficient additively, benefit multiplicatively through the coupling efficiency η. When coupling is absent, the net coefficient reduces to −c < 0 for any benefit magnitude, so an uncoupled apparatus is actively purged by purifying selection rather than merely unrewarded. Speculative fixation is thereby forbidden: a receptor system cannot persist in a lineage while awaiting the later evolution of the architecture that would make it useful. This closes the possibility that complex signalling apparatus drifts neutrally into existence before acquiring function. The prediction is tested against the two best-characterised unicellular GPCR systems — the Ste2/Ste3 pheromone receptors of Saccharomyces and the cAR1–4 cAMP receptors of Dictyostelium discoideum — using published effective population sizes (≈ 7–9 × 10⁶ and ≈ 1.5 × 10⁷ respectively). Both couple to fitness-critical outputs from the outset and satisfy the fixation condition by wide margins, confirming the account rather than contradicting it. A section on why nervous systems satisfy the coupling condition through developmental co-specification of receptor and circuit is included, together with four falsifiable predictions and a sensitivity analysis over both empirical anchors. The general moral is that the decisive bioenergetic constraints on evolution may not be constraints of magnitude: a cost that is trivially small can still be decisive if it is paid unconditionally while the corresponding benefit is not. Monte Carlo simulation code is fully deterministic given the fixed seed and is openly deposited at https://doi.org/10.5281/zenodo.21915807.