The Arabidopsis Framework Model version 2 predicts the organism-level effects of circadian clock gene mis-regulation

  1. Yin Hoon Chew
  2. Daniel D Seaton
  3. Virginie Mengin
  4. Anna Flis
  5. Sam T Mugford
  6. Gavin M George
  7. Michael Moulin
  8. Alastair Hume
  9. Samuel C Zeeman
  10. Teresa B Fitzpatrick
  11. Alison M Smith
  12. Mark Stitt
  13. Andrew J Millar

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Abstract

Predicting a multicellular organism’s phenotype quantitatively from its genotype is challenging, as genetic effects must propagate across scales. Circadian clocks are intracellular regulators that control temporal gene expression patterns and hence metabolism, physiology and behaviour. Here we explain and predict canonical phenotypes of circadian timing in a multicellular, model organism. We used diverse metabolic and physiological data to combine and extend mathematical models of rhythmic gene expression, photoperiod-dependent flowering, elongation growth and starch metabolism within a Framework Model for the vegetative growth of Arabidopsis thaliana, sharing the model and data files in a structured, public resource. The calibrated model predicted the effect of altered circadian timing upon each particular phenotype in clock-mutant plants under standard laboratory conditions. Altered night-time metabolism of stored starch accounted for most of the decrease in whole-plant biomass, as previously proposed. Mobilization of a secondary store of malate and fumarate was also mis-regulated, accounting for any remaining biomass defect. The three candidate mechanisms tested did not explain this organic acid accumulation. Our results link genotype through specific processes to higher-level phenotypes, formalizing our understanding of a subtle, pleiotropic syndrome at the whole-organism level, and validating the systems approach to understand complex traits starting from intracellular circuits.

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  1. Version published to 10.1093/insilicoplants/diac010
  2. ScreenIT

    SciScore for 10.1101/105437: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Area analysis was conducted using ImageJ (Schneider et al. 2012).
    ImageJ
    suggested: (ImageJ, RRID:SCR_003070)
    Modelling methods: Development of the FMv2 in Matlab (Mathworks, Cambridge, UK), model equations, experimental data for model calibration and simulation procedures are described in the Supporting Information Methods section.
    Matlab
    suggested: (MATLAB, RRID:SCR_001622)
    Zenodo. https://doi.org/10.5281/zenodo.??[
    Zenodo
    suggested: (ZENODO, RRID:SCR_004129)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Extensions of the Framework Model (Supporting Information Table 2) might test other critical rhythmic functions, such as photosynthesis, and address the nutrient and water limitations that prevail in field conditions. Even in our well-watered conditions, the prr7prr9 clock mutants had consistently lower water content than wild-type plants (Supporting Information Figure 9k), suggesting another tractable effect that might be mediated by circadian misregulation of aquaporins and/or abscisic acid (Adams et al. 2018, Prado et al. 2019). Whole-organism physiology could also be understood (explained and predicted) quantitatively in other multicellular species (Le Novere 2015), for example using clock and metabolic models in animals and humans to understand body composition (Peek et al. 2013).

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

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  3. Version published to 10.1101/105437v2 on bioRxiv
  4. Version published to 10.1101/105437v1 on bioRxiv