title: Systematic perturbation of cytoskeletal function reveals a linear scaling relationship between cell geometry and fitness.
abstract: Diversification 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.
authors.affiliation: Bio-X Program, Stanford University, Stanford, CA 94305, USA; Department of Bioengineering, Stanford University, Stanford, CA 94305, USA. Electronic address: rmonds@syntheticgenomics.com.
authors.forename: Russell D
authors.initials: RD
authors.lastname: Monds
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
authors.forename: Timothy K
authors.initials: TK
authors.lastname: Lee
authors.affiliation: Biophysics Program, Stanford University, Stanford, CA 94305, USA.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Colavin
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
authors.forename: Tristan
authors.initials: T
authors.lastname: Ursell
authors.affiliation: Bio-X Program, Stanford University, Stanford, CA 94305, USA.
authors.forename: Selwyn
authors.initials: S
authors.lastname: Quan
authors.affiliation: Department of Biology and Biochemistry, University of Houston, Houston, TX 77204, USA.
authors.forename: Tim F
authors.initials: TF
authors.lastname: Cooper
authors.affiliation: Bio-X Program, Stanford University, Stanford, CA 94305, USA; Department of Bioengineering, Stanford University, Stanford, CA 94305, USA; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: kchuang@stanford.edu.
authors.forename: Kerwyn Casey
authors.initials: KC
authors.lastname: Huang
mesh_terms: D000483:Alleles; D002999:Clone Cells; D003599:Cytoskeleton / Q000378:metabolism*; D019020:Directed Molecular Evolution; D004777:Environment; D004926:Escherichia coli / Q000166:cytology* / Q000235:genetics* / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000378:metabolism; D056084:Genetic Fitness; D009154:Mutation
chemical_list: D029968:Escherichia coli Proteins; C078473:MreB protein, E coli