Characterization of dependencies between growth and division in budding yeast

Abstract

Cell growth and division are processes vital to the proliferation and development of life. Coordination between these two processes has been recognized for decades in a variety of organisms. In the budding yeast Saccharomyces cerevisiae, this coordination or 'size control' appears as an inverse correlation between cell size and the rate of cell-cycle progression, routinely observed in G 1 prior to cell division commitment. Beyond this point, cells are presumed to complete S/G 2 /M at similar rates and in a size-independent manner. As such, studies of dependence between growth and division have focused on G 1 . Moreover, in unicellular organisms, coordination between growth and division has commonly been analysed within the cycle of a single cell without accounting for correlations in growth and division characteristics between cycles of related cells. In a comprehensive analysis of three published time-lapse microscopy datasets, we analyse both intra-and inter-cycle dependencies between growth and division, revisiting assumptions about the coordination between these two processes. Interestingly, we find evidence (i) that S/G 2 /M durations are systematically longer in daughters than in mothers, (ii) of dependencies between S/G 2 /M and size at budding that echo the classical G 1 dependencies, and (iii) in contrast with recent bacterial studies, of negative dependencies between size at birth and size accumulated during the cell cycle. In addition, we develop a novel hierarchical model to uncover inter-cycle dependencies, and we find evidence for such dependencies in cells growing in sugar-poor environments. Our analysis highlights the need for experimentalists and modellers to account for new sources of cell-to-cell variation in growth and division, and our model provides a formal statistical framework for the continued study of dependencies between biological processes.

Multiple inputs ensure yeast cell size homeostasis during cell cycle progression

“…This phenomenon explains the previously reported ( Cookson et al, 2005 ) progressive shortening of the cell cycle duration with the replicative age of the cell (see also Figure 1—figure supplement 9 ). Also, our result recapitulate the systematic shorter S/G2/M interval in mother cells compared to daughters that was recently measured( Mayhew et al, 2017 ). Over, these findings illustrate the power of our technique to quantitatively measure the temporal distribution of cell cycle intervals.…”

Scaling of G1 Duration with Population Doubling Time by a Cyclin in Saccharomyces cerevisiae

“…Figure 1, B and D), in agreement with observations from other groups(Anastasia et al 2012;Ferrezuelo et al 2012;Dowling et al 2014;Soifer and Barkai 2014;Cerulus et al 2016;Mayhew et al 2017;Garmendia-Torres et al 2018).…”

Details Matter: Noise and Model Structure Set the Relationship between Cell Size and Cell Cycle Timing

“…Adder correlations in diploid budding yeast cells are robust across a range of growth media, and show that passage through Start cannot follow the previously favored “size threshold” policy; a threshold in volume at Start would cause any correlation between cell size at birth and division to vanish. These correlations also highlight a potential difference in size regulation between haploid and diploid cells, since it has been noted recently that adder behavior is not observed in haploid daughter cells (Mayhew et al, 2017 ). Despite this, adder size correlations in diploid cells may be consistent with the molecular mechanism outlined above: in the idealized noiseless case it has been shown that a dilution model compatible with the Whi5 dilution hypothesis can reproduce these adder correlations between volume at birth and at division (Soifer et al, 2016 ).…”

“…This assumption stands in apparent opposition to observations in haploids that the concentration of Whi5 in the bud nucleus is higher than in the main cell nucleus at cell division (Liu et al, 2015 ; Schmoller et al, 2015 ). Further work should investigate this discrepancy by studying the distribution of Whi5 between mother and daughter at cell division in diploid cells, since these are the relevant cell type to study adder behavior (Soifer et al, 2016 ; Mayhew et al, 2017 ). Recent work has also demonstrated that adder-like behavior may be generated in a Whi5 dilution model by assuming dynamical changes in Cln3 concentration during G1, in addition to a constant abundance of Whi5 at birth (Delarue et al, 2017 ).…”