1. Fundamental behaviors emerge from simulations of a living minimal cell.
- Author
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Thornburg ZR, Bianchi DM, Brier TA, Gilbert BR, Earnest TM, Melo MCR, Safronova N, Sáenz JP, Cook AT, Wise KS, Hutchison CA 3rd, Smith HO, Glass JI, and Luthey-Schulten Z
- Subjects
- Adenosine Triphosphate metabolism, Cell Cycle genetics, Cell Proliferation genetics, Cells metabolism, DNA Replication genetics, Gene Expression Regulation, Imaging, Three-Dimensional, Kinetics, Lipids chemistry, Metabolic Networks and Pathways, Metabolome, Molecular Sequence Annotation, Nucleotides metabolism, Thermodynamics, Time Factors, Cells cytology, Computer Simulation
- Abstract
We present a whole-cell fully dynamical kinetic model (WCM) of JCVI-syn3A, a minimal cell with a reduced genome of 493 genes that has retained few regulatory proteins or small RNAs. Cryo-electron tomograms provide the cell geometry and ribosome distributions. Time-dependent behaviors of concentrations and reaction fluxes from stochastic-deterministic simulations over a cell cycle reveal how the cell balances demands of its metabolism, genetic information processes, and growth, and offer insight into the principles of life for this minimal cell. The energy economy of each process including active transport of amino acids, nucleosides, and ions is analyzed. WCM reveals how emergent imbalances lead to slowdowns in the rates of transcription and translation. Integration of experimental data is critical in building a kinetic model from which emerges a genome-wide distribution of mRNA half-lives, multiple DNA replication events that can be compared to qPCR results, and the experimentally observed doubling behavior., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
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