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

Sidário Rodrigues Malheiros-junior

doi:10.5281/zenodo.21910283

August 12, 2026Open Access

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

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Key Points

To test whether energetic costs constrain the evolutionary fixation and maintenance of complex GPCR signaling systems in unicellular organisms.
Calculated bioenergetic accounting for a complete GPCR signalling unit (~2700 residues) at physiological copy numbers.
Performed Monte Carlo simulations of the drift-barrier fixation condition across biologically plausible parameter space (N = 200,000 draws).
Assessed theoretical models using empirical data from Saccharomyces (Ste2/Ste3) and Dictyostelium discoideum (cAR1–4) with published effective population sizes.
A complete GPCR signaling unit requires approximately 0.2% of the cellular energy budget per generation, achieving fixation across 55.8% of parameter space compared to 73.9% for bacterial two-component sensors.
Prohibitive energetic constraints require unphysiologically high expression (~5 × 10⁵ copies per cell), indicating that uncoupled systems are purged by purifying selection because costs are paid unconditionally while benefits require downstream coupling.
Pheromone receptors in Saccharomyces (Ne ≈ 7–9 × 10⁶) and cAMP receptors in Dictyostelium (Ne ≈ 1.5 × 10⁷) satisfy fixation conditions by wide margins because they couple to fitness-critical outputs from the outset.

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Implication

Computational modeling reveals energetic costs do not prevent GPCR fixation in unicellular organisms, indicating structural downstream coupling dictates evolutionary selection.

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Sidário Rodrigues Malheiros-junior (2026) studied this question.

synapsesocial.com/papers/6a7ec764b70b84ec8b913b01 https://doi.org/10.5281/zenodo.21910283

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

Key Points

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

Key Points

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