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Phenotypic heterogeneity in lag reflects an evolutionarily stable bet-hedging strategy

Created on 05 Nov 2025

Authors

George, A. V., Wingreen, N. S., Reddy, G.

Abstract

Single-cell experiments in yeast reveal two distinct heritable phenotypes - `arresters' and `recoverers' - when a clonal population experiences a negative shift in its growth environment. Recoverers exhibit a variable yet finite lag before resuming growth in the new environment, whereas arresters remain in a non-growing, arrested state until more favorable conditions return. Although the diversification of individual cells into arresters and recoverers is a robust phenomenon, it remains unclear whether this coexistence constitutes an evolutionarily stable strategy. Here, we demonstrate that a heterogeneous strategy composed of both arrester and recoverer phenotypes maximizes long-term population fitness across a broad spectrum of growth-lag trade-offs. Our analysis employs a dynamic programming framework to identify the fitness-maximizing distribution of phenotypes for populations that stochastically switch between preferred and non-preferred environments. We propose a minimal model incorporating metabolism, growth, and enzyme allocation to explain the physiological origin of a power-law growth-lag trade-off that favors phenotypic heterogeneity. The theory predicts a nontrivial relationship between the fraction of recoverers and their lag time, which aligns with existing data from wild yeast strains, evolved isolates, and variations in pre-shift growth conditions. This relationship suggests an evolutionary `rheostat'-like mechanism that enables populations to rapidly adapt to changing environmental conditions.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 05 Nov 2025.

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