2025/07/09 by Mathéo Delvenne, Vincent Vandenbroucke, Lucas Henrion +6 · 1 voice · 1 citation
Biochemistry, Genetics and Molecular Biology · #Gene Regulatory Network Analysis
paper · pdf · doi:10.1101/2025.07.05.663304
openalex publication_date 2025/07/09 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/14
Abstract We present findings on a Fitness–Entropy Compensation (FEC) mechanism which offsets the activation of gene circuits that compromise survival. It counteracts the resulting fitness reduction by increasing the diversity in gene expression among individual cells within the population. This diversity, quantified by the Shannon entropy, enables cells with lower expression levels to support the survival of the entire population. We investigated the presence of FEC in a range of synthetic and stress-related genetic circuits in continuous culture. Our results reveal that it effectively stabilizes cell populations by mitigating the detrimental trade-offs between growth and gene expression. This stabilization is due to the reduced growth rate of the induced phenotype that leads to environmental changes, decreases induction strength, and promotes escape from unfit states. These findings suggest that the FEC mechanism may be a universal strategy for stabilization in various cellular systems and set the basis for a quantitative description of the trade-off between growth and gene expression and its consequences at the population level.