title: Noise-driven growth rate gain in clonal cellular populations.
abstract: Cellular populations in both nature and the laboratory are composed of phenotypically heterogeneous individuals that compete with each other resulting in complex population dynamics. Predicting population growth characteristics based on knowledge of heterogeneous single-cell dynamics remains challenging. By observing groups of cells for hundreds of generations at single-cell resolution, we reveal that growth noise causes clonal populations of Escherichia coli to double faster than the mean doubling time of their constituent single cells across a broad set of balanced-growth conditions. We show that the population-level growth rate gain as well as age structures of populations and of cell lineages in competition are predictable. Furthermore, we theoretically reveal that the growth rate gain can be linked with the relative entropy of lineage generation time distributions. Unexpectedly, we find an empirical linear relation between the means and the variances of generation times across conditions, which provides a general constraint on maximal growth rates. Together, these results demonstrate a fundamental benefit of noise for population growth, and identify a growth law that sets a "speed limit" for proliferation.
authors.affiliation: Department of Basic Science, Graduate School of Arts and Sciences, University of Tokyo, Tokyo 153-8902, Japan;
authors.forename: Mikihiro
authors.initials: M
authors.lastname: Hashimoto
authors.affiliation: Department of Basic Science, Graduate School of Arts and Sciences, University of Tokyo, Tokyo 153-8902, Japan;
authors.forename: Takashi
authors.initials: T
authors.lastname: Nozoe
authors.affiliation: Department of Basic Science, Graduate School of Arts and Sciences, University of Tokyo, Tokyo 153-8902, Japan;
authors.forename: Hidenori
authors.initials: H
authors.lastname: Nakaoka
authors.affiliation: Department of Basic Science, Graduate School of Arts and Sciences, University of Tokyo, Tokyo 153-8902, Japan;
authors.forename: Reiko
authors.initials: R
authors.lastname: Okura
authors.affiliation: Department of Basic Science, Graduate School of Arts and Sciences, University of Tokyo, Tokyo 153-8902, Japan;
authors.forename: Sayo
authors.initials: S
authors.lastname: Akiyoshi
authors.affiliation: Department of Basic Science, Graduate School of Arts and Sciences, University of Tokyo, Tokyo 153-8902, Japan; Research Center for Complex Systems Biology, University of Tokyo, Tokyo 153-8902, Japan;
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Kaneko
authors.affiliation: Department of Biology, Center for Genomics and Systems Biology, New York University, New York, NY 10003; Department of Physics, New York University, New York, NY 10003.
authors.forename: Edo
authors.initials: E
authors.lastname: Kussell
authors.affiliation: Department of Basic Science, Graduate School of Arts and Sciences, University of Tokyo, Tokyo 153-8902, Japan; Research Center for Complex Systems Biology, University of Tokyo, Tokyo 153-8902, Japan; cwaka@mail.ecc.u-tokyo.ac.jp.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Wakamoto
mesh_terms: D002455:Cell Division; D044085:Microfluidics; D008954:Models, Biological
keywords: age-structured population model; cell lineage analysis; growth law; growth noise; microfluidics