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

Abstract

Dormancy 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 muchwithin 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 with their degradations, causing gene-expressing ability to eventually vanish and, thus, death. Our work provides a systems-level view of dormancy-to-death transition.

Sporulation: A response to starvation in the fission yeast Schizosaccharomyces pombe

“…Nitrogen starvation, the optimum condition for extending CLS in S. pombe , arrests cells in the G 0 phase to confer survival for approximately one month (Ohtsuka et al, 2017 ; Su et al, 1996 ). However, the dormancy of spores, including those of S. pombe , extends lifespan through an unknown mechanism (Maire et al, 2020 ). Furthermore, the duration of survival of S. pombe spores remains undetermined.…”

“…Although spores likely extend lifespan without utilizing external nutrients, lipid droplets, which are membrane monolayer organelles primarily comprised of the neutral lipids triacylglycerol and sterol esters, may contribute (Thiam et al, 2013 ; Yang et al, 2017 ). A study of the death of S. cerevisiae spores suggests that a chronological decrease in the molecules required for the transcriptional machinery reduces the expression levels of endogenous genes, which reduces the opportunities for germination, leading to death (Maire et al, 2020 ). More than 90% of S. cerevisiae spores in water at 30℃ die within approximately 2 months (Maire et al, 2020 ), which does not seem to be a major difference from the survival period of S. pombe spores (Figure 4 ), suggesting that the ability to extend the survival period by sporulation is comparable in these yeasts.…”

“…A study of the death of S. cerevisiae spores suggests that a chronological decrease in the molecules required for the transcriptional machinery reduces the expression levels of endogenous genes, which reduces the opportunities for germination, leading to death (Maire et al, 2020 ). More than 90% of S. cerevisiae spores in water at 30℃ die within approximately 2 months (Maire et al, 2020 ), which does not seem to be a major difference from the survival period of S. pombe spores (Figure 4 ), suggesting that the ability to extend the survival period by sporulation is comparable in these yeasts. Nevertheless, major questions, such as how spores maintain life, remain, despite the newly developed understanding of the factors that influence the survival of spores.…”

Low‐Molecular Weight Compounds that Extend the Chronological Lifespan of Yeasts, Saccharomyces cerevisiae, and Schizosaccharomyces pombe

“…One is whether to undergo a sexual differentiation response accompanied by meiosis and produce spores with high stress tolerance and longevity, and the other is whether to enter the stationary phase, G 0 phase, which is inferior to sporulation as a survival strategy but has a high stress tolerance and long CLS. [20][21][22][23] Such nutritional restriction can easily control CLS of yeast, and nutritional restriction that does not cause malnutrition can also extend the lifespan of higher organisms. [5,24] Third, drugs can extend the lifespan of various organisms.…”

Wild yeast isolation by middle school students reveals features of North American oak populations ofSaccharomyces cerevisiaeandKluyveromyces lactis

“…Early investigations into the S. cerevisiae life cycle funded in part by beer industries in Denmark and the United States (Winge, 1935; Lindegren, 1945) revealed that while diploid yeast typically proliferate via budding (i.e., vegetatively), when starved for nitrogen most natural isolates are able to undergo meiosis accompanied by sporulation to produce haploid spores encased in specialized, stress-resistant cell walls. Without nutrients, a spore remains dormant and for weeks or longer retains the ability to germinate upon restoration of nutrients and either mate with an adjacent haploid cell or proliferate by budding (Brengues et al ., 2002; Maire et al ., 2020). Mating occurs only between haploid cells of compatible mating types, a with ⍺.…”