scholarly journals Coupling among growth rate response, metabolic cycle, and cell division cycle in yeast

2011 ◽  
Vol 22 (12) ◽  
pp. 1997-2009 ◽  
Author(s):  
Nikolai Slavov ◽  
David Botstein

We studied the steady-state responses to changes in growth rate of yeast when ethanol is the sole source of carbon and energy. Analysis of these data, together with data from studies where glucose was the carbon source, allowed us to distinguish a “universal” growth rate response (GRR) common to all media studied from a GRR specific to the carbon source. Genes with positive universal GRR include ribosomal, translation, and mitochondrial genes, and those with negative GRR include autophagy, vacuolar, and stress response genes. The carbon source–specific GRR genes control mitochondrial function, peroxisomes, and synthesis of vitamins and cofactors, suggesting this response may reflect the intensity of oxidative metabolism. All genes with universal GRR, which comprise 25% of the genome, are expressed periodically in the yeast metabolic cycle (YMC). We propose that the universal GRR may be accounted for by changes in the relative durations of the YMC phases. This idea is supported by oxygen consumption data from metabolically synchronized cultures with doubling times ranging from 5 to 14 h. We found that the high oxygen consumption phase of the YMC can coincide exactly with the S phase of the cell division cycle, suggesting that oxidative metabolism and DNA replication are not incompatible.

2012 ◽  
Vol 23 (10) ◽  
pp. 1986-1997 ◽  
Author(s):  
Nikolai Slavov ◽  
Edoardo M. Airoldi ◽  
Alexander van Oudenaarden ◽  
David Botstein

The respiratory metabolic cycle in budding yeast (Saccharomyces cerevisiae) consists of two phases that are most simply defined phenomenologically: low oxygen consumption (LOC) and high oxygen consumption (HOC). Each phase is associated with the periodic expression of thousands of genes, producing oscillating patterns of gene expression found in synchronized cultures and in single cells of slowly growing unsynchronized cultures. Systematic variation in the durations of the HOC and LOC phases can account quantitatively for well-studied transcriptional responses to growth rate differences. Here we show that a similar mechanism—transitions from the HOC phase to the LOC phase—can account for much of the common environmental stress response (ESR) and for the cross-protection by a preliminary heat stress (or slow growth rate) to subsequent lethal heat stress. Similar to the budding yeast metabolic cycle, we suggest that a metabolic cycle, coupled in a similar way to the ESR, in the distantly related fission yeast, Schizosaccharomyces pombe, and in humans can explain gene expression and respiratory patterns observed in these eukaryotes. Although metabolic cycling is associated with the G0/G1 phase of the cell division cycle of slowly growing budding yeast, transcriptional cycling was detected in the G2 phase of the division cycle in fission yeast, consistent with the idea that respiratory metabolic cycling occurs during the phases of the cell division cycle associated with mass accumulation in these divergent eukaryotes.


2016 ◽  
Vol 27 (1) ◽  
pp. 64-74 ◽  
Author(s):  
Anthony J. Burnetti ◽  
Mert Aydin ◽  
Nicolas E. Buchler

Cells have evolved oscillators with different frequencies to coordinate periodic processes. Here we studied the interaction of two oscillators, the cell division cycle (CDC) and the yeast metabolic cycle (YMC), in budding yeast. Previous work suggested that the CDC and YMC interact to separate high oxygen consumption (HOC) from DNA replication to prevent genetic damage. To test this hypothesis, we grew diverse strains in chemostat and measured DNA replication and oxygen consumption with high temporal resolution at different growth rates. Our data showed that HOC is not strictly separated from DNA replication; rather, cell cycle Start is coupled with the initiation of HOC and catabolism of storage carbohydrates. The logic of this YMC–CDC coupling may be to ensure that DNA replication and cell division occur only when sufficient cellular energy reserves have accumulated. Our results also uncovered a quantitative relationship between CDC period and YMC period across different strains. More generally, our approach shows how studies in genetically diverse strains efficiently identify robust phenotypes and steer the experimentalist away from strain-specific idiosyncrasies.


2014 ◽  
Author(s):  
Nikolai Slavov ◽  
David Botstein ◽  
Amy Caudy

Yeast cells grown in culture can spontaneously synchronize their respiration, metabolism, gene expression and cell division. Such metabolic oscillations in synchronized cultures reflect single-cell oscillations, but the relationship between the oscillations in single cells and synchronized cultures is poorly understood. To understand this relationship and the coordination between metabolism and cell division, we collected and analyzed DNA-content, gene-expression and physiological data, at hundreds of time-points, from cultures metabolically-synchronized at different growth rates, carbon sources and biomass densities. The data enabled us to extend and generalize our mechanistic model, based on ensemble average over phases (EAP), connecting the population-average gene-expression of asynchronous cultures to the gene-expression dynamics in the single-cells comprising the cultures. The extended model explains the carbon-source specific growth-rate responses of hundreds of genes. Our physiological data demonstrate that the frequency of metabolic cycling in synchronized cultures increases with the biomass density, suggesting that this cycling is an emergent behavior, resulting from the entraining of the single-cell metabolic cycle by a quorum-sensing mechanism, and thus underscoring the difference between metabolic cycling in single cells and in synchronized cultures. Measurements of constant levels of residual glucose across metabolically synchronized cultures indicate that storage carbohydrates are required to fuel not only the G1/S transition of the division cycle but also the metabolic cycle. Despite the large variation in profiled conditions and in the scale of their dynamics, most genes preserve invariant dynamics of coordination with each other and with the rate of oxygen consumption. Similarly, the G1/S transition always occurs at the beginning, middle or end of the high oxygen consumption phases, analogous to observations in human and drosophila cells. These results highlight evolutionary conserved coordination among metabolism, cell growth and division.


2017 ◽  
Author(s):  
Graeme J. Gowans ◽  
Alicia N. Schep ◽  
Ka Man Wong ◽  
Devin A. King ◽  
William J. Greenleaf ◽  
...  

ABSTRACTAdaptive survival requires the coordination of nutrient availability with expenditure of cellular resources. For example, in nutrient-limited environments, 50% of all S. cerevisiae genes synchronize and exhibit periodic bursts of expression in coordination with respiration and cell division in the Yeast Metabolic Cycle (YMC). Despite the importance of metabolic and proliferative synchrony, the majority of YMC regulators are currently unknown. Here we demonstrate that the INO80 chromatin-remodelling complex is required to coordinate respiration and cell division with periodic gene expression. Specifically, INO80 mutants have severe defects in oxygen consumption and promiscuous cell division that is no longer coupled with metabolic status. In mutant cells, chromatin accessibility of periodic genes, including TORC-responsive genes, is relatively static, concomitant with severely attenuated gene expression. Collectively, these results reveal that the INO80 complex mediates metabolic signaling to chromatin in order to restrict proliferation to metabolically optimal states.


1968 ◽  
Vol 14 (11) ◽  
pp. 1217-1224 ◽  
Author(s):  
Mary M. Grula ◽  
R. W. Smith ◽  
C. F. Parham ◽  
E. A. Grula

The species of Erwinia used in cell division studies (Grula 1960a) will grow on L- or D-aspartic acid, but no other amino acid, as a sole source of carbon, nitrogen, and energy. Ammonia is utilizable as a sole source of nitrogen; in this case the rate and extent of growth are significantly influenced by the carbon source. Of all compounds tested, malic acid supports the most rapid and abundant growth in an ammonium chloride – mineral salts medium. Added pantothenate often stimulates growth in ammonium chloride media, but not in aspartic acid media. Growth in an ammonium chloride – glucose – salts medium is rather slow and limited. Marked stimulation occurs by supplementation with intermediates of the Krebs cycle, even though the compound supports little or no growth as a sole carbon source. Neither L-glutamic acid nor α-ketoglutaric acid supports growth as a sole carbon source; this is believed to result from impermeability of the cell to these compounds.


Development ◽  
1975 ◽  
Vol 33 (2) ◽  
pp. 419-434
Author(s):  
J. H. Lewis

Given the growth rate throughout an embryonic rudiment, one can calculate how its parts must shift as it gets bigger, and so plot fate maps showing their future positions. The calculation is done here for the chick wing-bud from stage 18 to stage 25, using published data for mitotic index and cell packing density, and new measurements of size and shape. Two main findings are: (1) the wing-bud in this period elongates almost uniformly along itsproximodistal axis. (2) Each limb segment derives from the tissue generated by one cell division cycle in the ‘progress zone’ at the tip.


2001 ◽  
Vol 120 (5) ◽  
pp. A501-A501
Author(s):  
U HAUGWITZ ◽  
M WIEDMANN ◽  
K SPIESBACH ◽  
K ENGELAND ◽  
J MOSSNER

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