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Research Article

Metabolic cycling without cell division cycling in respiring yeast

Nikolai Slavov, Joanna Macinskas, Amy Caudy, and David Botstein
PNAS November 22, 2011 108 (47) 19090-19095; https://doi.org/10.1073/pnas.1116998108
Nikolai Slavov
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  • For correspondence: nslavov@alum.mit.edu botstein@princeton.edu
Joanna Macinskas
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Amy Caudy
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David Botstein
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  • For correspondence: nslavov@alum.mit.edu botstein@princeton.edu
  1. Contributed by David Botstein, October 17, 2011 (sent for review September 12, 2011)

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    Fig. 1.

    Growth-rate (GR) changes in the yeast metabolic cycle and the cell division cycle. Changes in the relative duration of the phases of (A) the CDC and (B) the YMC (3). (C) Distributions of the number of mRNAs per cell of a ribosomal gene in an asynchronous culture growing at three growth rates.

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    Fig. 2.

    Oxygen, biomass, and DNA content data in a metabolically cycling nondividing culture. (A) Dissolved oxygen in the medium reflecting the oxygen consumption. The culture was sampled at the positions indicated by red circles. (B) Cell density at each of the sampled points. (C) Distribution of DNA content obtained by FACS counting 150,000 cells labeled with SYTOX Green. (D) Fraction of cells in the CDC phases as inferred from the DNA content.

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    Fig. 3.

    Global pattern of periodic gene expression in metabolically cycling cultures. (A) Hierarchically clustered, log2-transformed, gene-expression data from YMC cultures. (Left) The black bars at the top display dissolved oxygen and correspond to the expression levels in our batch culture (Fig. 2) relative to a glucose-limited culture, μ = 0.25 h−1. (Center) The blue bars correspond to the same data but centered to a zero mean for each gene. (Right) The magenta bars correspond to mean centered data from a continuous glucose-limited culture (10). The clustering is based on noncentered Pearson correlation computed from all data shown in the panel. The dissolved oxygen in the media of the two cultures is indicated by bars at the top (SI Appendix). (B) The expression levels of about 90% of the periodic genes (more than 3,000) have the same phase in the batch culture (Fig. 2) and in the continuous culture (10). These genes are ordered by phase of peak expression (Materials and Methods and SI Appendix).

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    Fig. 4.

    Genes annotated to the CDC are periodically expressed in a nondividing culture in correlation with the metabolic cycle. (Left) Expression levels relative to the reference (glucose limitation at μ = 0.25 h−1). (Center) The same data centered to mean zero. (Right) The growth-rate (GR) slopes of the corresponding genes in asynchronous cultures (2). We previously computed GR slopes by regressing transcript levels of asynchronous cultures against the growth rate (2, 3); positive GR slopes indicate increasing expression with growth rate, and negative GR slopes indicate decreasing expression.

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    Fig. 5.

    Composition of a continuous metabolically synchronized culture. A model for the composition of a metabolically synchronized culture consisting of three synchronized subpopulations depicted by a representative cell. Note that we do not have direct data for the oxygen consumption during the S/G2/M phases and that not all cells need to have the same number of metabolic cycles before entering S phase.

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Metabolic cycling without cell division cycling in respiring yeast
Nikolai Slavov, Joanna Macinskas, Amy Caudy, David Botstein
Proceedings of the National Academy of Sciences Nov 2011, 108 (47) 19090-19095; DOI: 10.1073/pnas.1116998108

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Metabolic cycling without cell division cycling in respiring yeast
Nikolai Slavov, Joanna Macinskas, Amy Caudy, David Botstein
Proceedings of the National Academy of Sciences Nov 2011, 108 (47) 19090-19095; DOI: 10.1073/pnas.1116998108
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