Dormancy-to-death transition in yeast spores occurs due to gradual loss of gene-expressing ability

Abstract

ABSTRACTDormancy is colloquially considered as extending lifespan by being still. Starved yeasts form dormant spores that wake-up (germinate) when nutrients reappear but cannot germinate (die) after some time. What sets their lifespans and how they age are open questions because what processes occur - and by how much - within each dormant spore remains unclear. With single-cell-level measurements, we discovered how dormant yeast spores age and die: spores have a quantifiable gene-expressing ability during dormancy that decreases over days to months until it vanishes, causing death. Specifically, each spore has a different probability of germinating that decreases because its ability to - without nutrients - express genes decreases, as revealed by a synthetic circuit that forces GFP expression during dormancy. Decreasing amounts of molecules required for gene expression - including RNA polymerases - decreases gene-expressing ability which then decreases chances of germinating. Spores gradually lose these molecules because they are produced too slowly compared to their degradations, causing gene-expressing ability to eventually vanish and, thus, death. Our work provides a systems-level view of dormancy-to-death transition.Short summaryThis study identifies systems-level quantities that decay during dormancy in Saccharomyces cerevisiae spores and thereby reveals the meaning of ageing for dormant yeast spores and shows that they die when their gene-expressing ability is irreversibly lost.HighlightsFor a given glucose concentration, a dormant yeast spore has a well-defined probability of germinating (“germination ability”).A spore’s germination ability positively correlates with its RNAP I-III levels and the gene-expression (GFP) level it can realize when the expression is forced without nutrients.Ageing during dormancy means gradual decreases in germination ability, RNAP levels, and GFP-level realizable when expression is forced.Spores die after sufficiently losing gene-expressing ability and drugs that inhibit gene expression during dormancy shorten spores’ lifespans (e.g., from months to a day).