Dormancy as a spectrum measuring spore’s proximity to death and to replicative life

How organisms with their lives ceased stay alive and what sets their lifespans are fundamental questions relevant for microbial spores. Starved microbes can form spores whose metabolism and gene-expressions are active for hours-to-days but nearly cease upon entering dormancy. Although dormant spores can wake-up (germinate) when nutrients reappear, they die - cannot germinate - after prolonged nutrient-absences. Previous studies identified several factors that affect spore revival. But how these and as-yet-unknown intracellular factors collectively encode a dormant spore9s lifespan remains poorly understood. Here we reveal an easy-to-measure, systems-level metric - a quantity that combines many intracellular factors - that accurately predicts dormant yeast-spores9 lifespans by establishing dormancy as a quantity that, without nutrients, decreases at a predictable rate, thereby revealing how dormant spores approach death. We discovered different glucose-concentrations germinating distinct percentages of yeast-spores, with low glucose-concentrations priming un-germinated spores to accelerate their germinations when more glucose appears hours-to-days later. Using a synthetic circuit, we quantified dormant spores9 gene-expressing ability without nutrients - a systems-level metric - whose value determines a minimum glucose-concentration required for guaranteeing germination and, for glucose concentrations below it, probability of germinating. Dormant spores9 gene-expressing ability predictably decreases over days-to-months, causing glucose-concentration required for germination to increase with predictable rates until going beyond a saturating value - spore9s moment of death. By introducing "dormancy spectrum" - a ruler that measures spore9s proximity to death (lifespan) and to replicative life (germination capacity) - and finding dormancy9s systems-level indicators, we unveiled hidden dynamics of dormant spores approaching death.