Engineered gene circuits often degrade over time due to mutation and selection. Here the authors use a host-aware modelling framework to develop genetic controllers to sustain synthetic gene expression. They identify a range of design trade-offs in production, robustness and long-term performance.

London SynBio afterwork talks and networking event on Thursday 25th of September

Abstract. Microbial communities are frequently organized into complex spatial structures, shaped by intrinsic cellular traits, interactions between communi

Nature - Cancer evolutionary dynamics are quantitatively inferred using a method, EVOFLUx, applied to fluctuating DNA methylation.

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ALT: a man in a suit standing in a greenhouse

In simple microbial populations, the fitness effects of most selected mutations are generally taken to be constant, independent of genotype frequency. This assumption underpins predictions about evolutionary dynamics, epistatic interactions, and the maintenance of genetic diversity in populations. Here, we systematically test this assumption using beneficial mutations from early generations of the Escherichia coli Long-Term Evolution Experiment (LTEE). Using flow cytometry-based competition assays, we find that frequency-dependent fitness effects are the norm rather than the exception, occurring in approximately 80\% of strain pairs tested. Most competitions exhibit negative frequency-dependence, where fitness advantages decline as mutant frequency increases. Furthermore, we demonstrate that the strength of frequency-dependence is predictable from invasion fitness measurements, with invasion fitness explaining approximately half of the biological variation in frequency-dependent slopes. Additionally, we observe violations of fitness transitivity in several strain combinations, indicating that competitive relationships cannot always be predicted from fitness relative to a single reference strain alone. Through high-resolution measurements of within-growth cycle dynamics, we show that simple resource competition explains a substantial portion of the frequency-dependence: when faster-growing genotypes dominate populations, they deplete shared resources more rapidly, reducing the time available for fitness differences to accumulate. Our results demonstrate that even in a simple model system designed to minimize ecological complexity, subtle ecological interactions between closely related genotypes create frequency-dependent selection that can fundamentally alter evolutionary dynamics. ### Competing Interest Statement The authors have declared no competing interest.

Announcing a new program, called STEPS, to simulate the dynamics of evolving microbial populations.