biostudies-literaturede Groot DHSchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (SNF)Dutch Research Council (NWO)Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschunge2211091120https://www.ebi.ac.uk/biostudies/studies/S-EPMC9974493biostudies-literatureUnknown120(8)Microbes in the wild face highly variable and unpredictable environments and are naturally selected for their average growth rate across environments. Apart from using sensory regulatory systems to adapt in a targeted manner to changing environments, microbes employ bet-hedging strategies where cells in an isogenic population switch stochastically between alternative phenotypes. Yet, bet-hedging suffers from a fundamental trade-off: Increasing the phenotype-switching rate increases the rate at which maladapted cells explore alternative phenotypes but also increases the rate at which cells switch out of a well-adapted state. Consequently, it is currently believed that bet-hedging strategies are effective only when the number of possible phenotypes is limited and when environments last for sProceedings of the National Academy of Sciences of the United States of AmericaEffective bet-hedging through growth rate dependent stability.PMC9974493310030_1849371228.191.283Tjalma AJvan Nimwegen Ede Groot DHBruggeman FJfalseEffective bet-hedging through growth rate dependent stability.Microbes in the wild face highly variable and unpredictable environments and are naturally selected for their average growth rate across environments. Apart from using sensory regulatory systems to adapt in a targeted manner to changing environments, microbes employ bet-hedging strategies where cells in an isogenic population switch stochastically between alternative phenotypes. Yet, bet-hedging suffers from a fundamental trade-off: Increasing the phenotype-switching rate increases the rate at which maladapted cells explore alternative phenotypes but also increases the rate at which cells switch out of a well-adapted state. Consequently, it is currently believed that bet-hedging strategies are effective only when the number of possible phenotypes is limited and when environments last for s2023-01-01T00:00:00Z2023 Feb2025-04-26T10:22:10.848Z2025-04-06T13:18:11.659ZS-EPMC99744933678051810.1073/pnas.2211091120