Growth rate-dependent mutations and phenotypic switching facilitate rapid adaptation
File(s)
Article in press
Author(s)
Anton, Grishechkin
Karin, Omer
Type
Journal Article
Abstract
The mutation rates of many species are regulated in response to internal and external conditions. Studies in several model organisms have shown that mutation rates can be modulated by the organism’s growth rate, particularly through stress-induced mutagenesis. Here, we investigate the functional consequences of this coupling. Using a model of asexual evolution on a high-dimensional, single-peaked fitness landscape, we show that regulating mutation rate through growth rate provides an efficient strategy for rapid adaptation. This mechanism maximizes growth by balancing mutation and selection pressures. We approximate the optimal coupling as a biphasic response function that prescribes a low, constant mutation rate at high growth rates, which gradually increases once growth falls below a critical threshold. This adaptive strategy depends on two key parameters: mutational gain and critical growth rate, both determined by environmental conditions. This raises the question of how organisms establish these parameters in fluctuating environments. We demonstrate that weak selection in well-adapted populations, combined with long-term phenotypic fluctuations, can generate variability in these parameters. Such standing variation prepares populations for rapid evolution following environmental change. Our findings connect this adaptive strategy to specific molecular regulatory circuits and provide predictions for sequential antibiotic treatment regimens.
Date Issued
2026-06-16
Date Acceptance
2026-05-28
Citation
npj Systems Biology and Applications, 2026
ISSN
2056-7189
Publisher
Nature Portfolio
Journal / Book Title
npj Systems Biology and Applications
Copyright Statement
© The Author(s) 2026. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
License URL
Identifier
10.1038/s41540-026-00758-4
Subjects
Grishechkin, A., Karin, O. Growth rate-dependent mutations and phenotypic switching facilitate rapid adaptation. npj Syst Biol Appl (2026) Adaptation
Mutation rate
Fisher's Geometric Model
Systems Biology
Evolvability
Publication Status
Published online
Date Publish Online
2026-06-16