Systematic Perturbation of Cytoskeletal Function Reveals a Linear Scaling Relationship between Cell Geometry and Fitness

TLDR

Cell size diversification is thought to arise through evolutionary optimization, yet causal links between geometry and fitness have not been directly demonstrated; bacterial fitness is known to scale linearly with cell size across a broad range, with feast‑or‑famine transitions and biophysical constraints influencing this relationship. The authors sought to identify a mutation that increases cell size via cytoskeletal perturbation and to assess its impact on fitness. They engineered a library of cytoskeletal mutants spanning a wide range of cell sizes and measured growth rates to test the relationship. Fitness increased linearly with cell size, with feast‑or‑famine growth transitions driving size‑dependent effects, while certain environments suppressed the advantage of larger cells, revealing biophysical and metabolic constraints. The work establishes laboratory evolution as a powerful framework for quantitatively linking morphology and fitness.

Abstract

Highlights•Genetic tools for fine-scale control of cell geometry are developed•Bacterial fitness scales linearly as a function of cell size over a wide range•Transitions between "feast-or-famine" regimes underlie size-dependent fitness effects•Cell-size fitness effects are subject to biophysical and metabolic constraintsSummaryDiversification of cell size is hypothesized to have occurred through a process of evolutionary optimization, but direct demonstrations of causal relationships between cell geometry and fitness are lacking. Here, we identify a mutation from a laboratory-evolved bacterium that dramatically increases cell size through cytoskeletal perturbation and confers a large fitness advantage. We engineer a library of cytoskeletal mutants of different sizes and show that fitness scales linearly with respect to cell size over a wide physiological range. Quantification of the growth rates of single cells during the exit from stationary phase reveals that transitions between "feast-or-famine" growth regimes are a key determinant of cell-size-dependent fitness effects. We also uncover environments that suppress the fitness advantage of larger cells, indicating that cell-size-dependent fitness effects are subject to both biophysical and metabolic constraints. Together, our results highlight laboratory-based evolution as a powerful framework for studying the quantitative relationships between morphology and fitness.Graphical abstract