PT - JOURNAL ARTICLE AU - Yoshikazu Hirate AU - Samuel Bottani AU - Wyming Lee Pang AU - Suzannah Rutherford TI - Programmed bet hedging in yeast responses to osmotic stress AID - 10.1101/039982 DP - 2016 Jan 01 TA - bioRxiv PG - 039982 4099 - http://biorxiv.org/content/early/2016/04/05/039982.short 4100 - http://biorxiv.org/content/early/2016/04/05/039982.full AB - Rapid reproduction contributes to evolutionary fitness but can be lethal under stress. Microbes are thought to limit risk in clonal populations by bet hedging; the stochastic expression of a low frequency of slow growing cells constitutively resistant to unpredictable environmental stresses including antibiotics. However fitness depends on rapid recovery and resumption of growth in potentially lethal environments whose severity and duration are also unpredictable. Here we describe trade-offs between osmotic stress-responsive signaling, survival and proliferation in 50 ecologically distinct strains of budding yeast. By contrast with prior examples, programmed bet hedging responses were heritable, stress-specific and varied continuously in our population. During rapid growth strong osmotic stress signaling promoted survival. Weak signaling predicted lower viability, intense rebound signaling and robust recovery. Older cultures survived and adapted to unprecedented stress with fitness depending on reproducible, strain-specific proportions of cells with divergent strategies. The most ‘cautious’ cells survive extreme stress without dividing; the most ‘reckless’ cells attempt to divide too soon and fail, killing both mother and daughter. Heritable proportions of cautious and reckless cells generate a tunable, rapidly diversifying template for microbial bet hedging that resembles natural variation and would evolve in different patterns of environmental stress.