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Horizontal and vertical growth of S. cerevisiae metabolic network.

ABSTRACT: BACKGROUND: The growth and development of a biological organism is reflected by its metabolic network, the evolution of which relies on the essential gene duplication mechanism. There are two current views about the evolution of metabolic networks. The retrograde model hypothesizes that a pathway evolves by recruiting novel enzymes in a direction opposite to the metabolic flow. The patchwork model is instead based on the assumption that the evolution is based on the exploitation of broad-specificity enzymes capable of catalysing a variety of metabolic reactions. RESULTS: We analysed a well-studied unicellular eukaryotic organism, S. cerevisiae, and studied the effect of the removal of paralogous gene products on its metabolic network. Our results, obtained using different paralog and network definitions, show that, after an initial period when gene duplication was indeed instrumental in expanding the metabolic space, the latter reached an equilibrium and subsequent gene duplications were used as a source of more specialized enzymes rather than as a source of novel reactions. We also show that the switch between the two evolutionary strategies in S. cerevisiae can be dated to about 350 million years ago. CONCLUSIONS: Our data, obtained through a novel analysis methodology, strongly supports the hypothesis that the patchwork model better explains the more recent evolution of the S. cerevisiae metabolic network. Interestingly, the effects of a patchwork strategy acting before the Euascomycete-Hemiascomycete divergence are still detectable today.

SUBMITTER: Grassi L

PROVIDER: S-EPMC3216907 | biostudies-other | 2011

REPOSITORIES: biostudies-other

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Horizontal and vertical growth of S. cerevisiae metabolic network.

Grassi Luigi L Tramontano Anna A

BMC evolutionary biology 20111014

<h4>Background</h4>The growth and development of a biological organism is reflected by its metabolic network, the evolution of which relies on the essential gene duplication mechanism. There are two current views about the evolution of metabolic networks. The retrograde model hypothesizes that a pathway evolves by recruiting novel enzymes in a direction opposite to the metabolic flow. The patchwork model is instead based on the assumption that the evolution is based on the exploitation of broad- ...[more]

PMID: 21999464

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Project description:IntroductionThe switch from quiescence (G0) into G1 and cell cycle progression critically depends on specific nutrients and metabolic capabilities. Conversely, metabolic networks are regulated by enzyme-metabolite interaction and transcriptional regulation that lead to flux modifications to support cell growth. How cells process and integrate environmental information into coordinated responses is challenging to analyse and not yet described quantitatively.ObjectivesTo quantitatively monitor the central carbon metabolism during G0 exit and the first 2 h after reentering the cell cycle from synchronized Saccharomyces cerevisiae.MethodsDynamic tailored 13C metabolic flux analysis was used to observe the intracellular metabolite flux changes, and the metabolome and proteome were observed to identify regulatory mechanisms.ResultsG0 cells responded immediately to an extracellular increase of glucose. The intracellular metabolic flux changed in time and specific events were observed. High fluxes into trehalose and glycogen synthesis were observed during the G0 exit. Both fluxes then decreased, reaching a minimum at t?=?65 min. Here, storage degradation contributed significantly (i.e. 21%) to the glycolytic flux. In contrast to these changes, the glucose uptake rate remained constant after the G0 exit. The flux into the oxidative pentose phosphate pathway was highest (29-fold increase, 36.4% of the glucose uptake) at t?=?65 min, while it was very low at other time points. The maximum flux seems to correlate with a late G1 state preparing for the S phase transition. In the G1/S phase (t?=?87 min), anaplerotic reactions such as glyoxylate shunt increased. Protein results show that during this transition, proteins belonging to clusters related with ribosome biogenesis and assembly, and initiation transcription factors clusters were continuously synthetised.ConclusionThe intracellular flux distribution changes dynamically and these major rearrangements highlight the coordinate reorganization of metabolic flux to meet requirements for growth during different cell state.

Project description:BackgroundEfforts to improve the computational reconstruction of the Saccharomyces cerevisiae biochemical reaction network and to refine the stoichiometrically constrained metabolic models that can be derived from such a reconstruction have continued since the first stoichiometrically constrained yeast genome scale metabolic model was published in 2003. Continuing this ongoing process, we have constructed an update to the Yeast Consensus Reconstruction, Yeast 5. The Yeast Consensus Reconstruction is a product of efforts to forge a community-based reconstruction emphasizing standards compliance and biochemical accuracy via evidence-based selection of reactions. It draws upon models published by a variety of independent research groups as well as information obtained from biochemical databases and primary literature.ResultsYeast 5 refines the biochemical reactions included in the reconstruction, particularly reactions involved in sphingolipid metabolism; updates gene-reaction annotations; and emphasizes the distinction between reconstruction and stoichiometrically constrained model. Although it was not a primary goal, this update also improves the accuracy of model prediction of viability and auxotrophy phenotypes and increases the number of epistatic interactions. This update maintains an emphasis on standards compliance, unambiguous metabolite naming, and computer-readable annotations available through a structured document format. Additionally, we have developed MATLAB scripts to evaluate the model's predictive accuracy and to demonstrate basic model applications such as simulating aerobic and anaerobic growth. These scripts, which provide an independent tool for evaluating the performance of various stoichiometrically constrained yeast metabolic models using flux balance analysis, are included as Additional files 1, 2 and 3.ConclusionsYeast 5 expands and refines the computational reconstruction of yeast metabolism and improves the predictive accuracy of a stoichiometrically constrained yeast metabolic model. It differs from previous reconstructions and models by emphasizing the distinction between the yeast metabolic reconstruction and the stoichiometrically constrained model, and makes both available as Additional file 4 and Additional file 5 and at http://yeast.sf.net/ as separate systems biology markup language (SBML) files. Through this separation, we intend to make the modeling process more accessible, explicit, transparent, and reproducible.

Project description:Researchers expect a high quality of biospecimens/data and value-added services from biobanks. Therefore, the concept of "biobank 3.0" was introduced so that biobanks could better meet the needs of stakeholders and maintain sustainable operations. Theoretically, the Taiwan Biobank (TWB) has already gone through the concepts of biobank 1.0 and 2.0. However, three challenges still need to be addressed before it can be transformed into a new generation of the TWB (namely, the TWB 3.0): (1) the difficulty of integrating other biobanks' resources, (2) the efficiency and effectiveness of the release and use of biospecimens/data, and (3) the development of income and revenue models of sustainability. To address these issues, this paper proposes a framework for the TWB 3.0 transformation based on a dual-pillar approach composed of a "physically" vertical integration driven by the TWB and a "virtually" horizontal network led by the National Health Research Institutes (NHRI) of Taiwan. Using prominent biobanks such as the Biobanking and BioMolecular Resources Research Infrastructure-European Research Infrastructure Consortium (BBMRI-ERIC), the UK Biobank, and the National Institutes of Health (NIH)'s All of Us Research Program as models, the TWB can strengthen its on-going TWB 2.0 operations in regional and/or international collaboration, increase the value of data collected and develop closer relationships with biobank participants and users. To these ends, the authors highlight key issues that include, but are not limited to, the harmonization of relevant ELSI standards for various biobanks' integrations; the value-added services and the efficiency of Big Data Era related research and/or precision medicine development, and financial concerns related to biobank sustainability. This paper concludes by discussing how greater participant engagement and the uptake of Information Technology (IT) and Artificial Intelligence (AI) applications can be used in partnership with vertical and horizontal integration as part of a four-pronged approach to promote biobank sustainability, and facilitate the TWB 3.0 transformation.

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Horizontal and vertical growth of S. cerevisiae metabolic network.

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Horizontal and vertical growth of S. cerevisiae metabolic network.

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