Division Asymmetry Drives Cell Size Variability in Budding Yeast
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Abstract
Cell size variability within proliferating populations reflects the interdependent regulation of cell growth and division as well as intrinsically stochastic effects. In budding yeast, the G1/S transition exerts strong size control in daughter cells, which manifests as the inverse correlation between how big a cell is when it is born and how much it grows in G1. However, mutations affecting this size control checkpoint only modestly influence population-wide size variability, often altering the coefficient of variation (CV) only by ∼10%. To resolve this paradox, we combine computational modeling and live-cell imaging to identify the principal determinants of cell size variability. Using an experimentally validated stochastic model of the yeast cell cycle, we perform parameter sensitivity analysis and find that division asymmetry between mothers and daughters is the dominant driver of CV, outweighing the effects of G1/S size control. Experimental measurements across genetic perturbations and growth conditions confirm a strong correlation between mother-daughter size asymmetry and population CV. These findings reconcile previous observations and show how asymmetric division operates in concert with G1/S size control to govern cell size heterogeneity.
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Our study analyzes the determinants of cell size variability in S. cerevisiae to identify mother-daughter asymmetry as a primary driver of the coefficient of variation (CV) of cell size within a population.
Hello! I really appreciated this work. The parameter–sensitivity analysis is especially nice for connecting the experimental results to elucidate the role of mother–daughter asymmetry.
One question I had: you mention that the cln3Δwhi5Δ mutant shows reduced mother–daughter asymmetry compared to what the pure timer model predicts, which seems like an interesting discrepancy. Do you have any hypotheses about what biological coordination or parameter correlations might explain this?
I also wondered whether the microscopy data used for the mother–daughter asymmetry analysis might be made publicly available? I think it would be a …
Our study analyzes the determinants of cell size variability in S. cerevisiae to identify mother-daughter asymmetry as a primary driver of the coefficient of variation (CV) of cell size within a population.
Hello! I really appreciated this work. The parameter–sensitivity analysis is especially nice for connecting the experimental results to elucidate the role of mother–daughter asymmetry.
One question I had: you mention that the cln3Δwhi5Δ mutant shows reduced mother–daughter asymmetry compared to what the pure timer model predicts, which seems like an interesting discrepancy. Do you have any hypotheses about what biological coordination or parameter correlations might explain this?
I also wondered whether the microscopy data used for the mother–daughter asymmetry analysis might be made publicly available? I think it would be a valuable resource for others in the field.
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