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6 Publications visible to you, out of a total of 6
The Arabidopsis Framework Model version 2 predicts the organism-level effects of circadian clock gene mis-regulation

Abstract (Expand)

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.

Authors: Yin Hoon Chew, Daniel D Seaton, Virginie Mengin, Anna Flis, Sam T Mugford, Gavin M George, Michael Moulin, Alastair Hume, Samuel C Zeeman, Teresa B Fitzpatrick, Alison M Smith, Mark Stitt, Andrew J Millar

Date Published: 1st Jul 2022

Publication Type: Journal

Linking circadian time to growth rate quantitatively via carbon metabolism

Abstract (Expand)

Summary paragraph Predicting a multicellular organism’s phenotype quantitatively from its genotype is challenging, as genetic effects must propagate up time and length scales. Circadian clocks are …length scales. Circadian clocks are intracellular regulators that control temporal gene expression patterns and hence metabolism, physiology and behaviour, from sleep/wake cycles in mammals to flowering in plants 1–3 . Clock genes are rarely essential but appropriate alleles can confer a competitive advantage 4,5 and have been repeatedly selected during crop domestication 3,6 . Here we quantitatively explain and predict canonical phenotypes of circadian timing in a multicellular, model organism. We used 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 growth of Arabidopsis thaliana 7–9 . The model predicted the effect of altered circadian timing upon each particular phenotype in clock-mutant plants. Altered night-time metabolism of stored starch accounted for most but not all of the decrease in whole-plant growth rate. Altered mobilisation of a secondary store of organic acids explained the remaining defect. Our results link genotype through specific processes to higher-level phenotypes, formalising 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.

Authors: Yin Hoon Chew, Daniel D. Seaton, Virginie Mengin, Anna Flis, Sam T. Mugford, Alison M. Smith, Mark Stitt, Andrew J Millar

Date Published: 6th Feb 2017

Publication Type: Tech report

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

Abstract (Expand)

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. Mobilisation of a secondary store of malate and fumarate was also mis-regulated, accounting for any remaining biomass defect. We test three candidate mechanisms for the accumulation of these organic acids. Our results link genotype through specific processes to higher-level phenotypes, formalising 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. This work updates the first biorXiv version, February 2017,with an expanded description and additional analysis of the same core data sets and the same FMv2 model, summary tables and supporting, follow-on data from three further studies with further collaborators. This biorXiv revision constitutes the second version of this report.

Authors: Yin Hoon Chew, Daniel D. Seaton, Virginie Mengin, Anna Flis, Sam T. Mugford, Gavin M. George, Michael Moulin, Alastair Hume, Samuel C. Zeeman, Teresa B. Fitzpatrick, Alison M. Smith, Mark Stitt, Andrew J. Millar

Date Published: 6th Feb 2017

Publication Type: Tech report

Defining the robust behaviour of the plant clock gene circuit with absolute RNA timeseries and open infrastructure

Abstract (Expand)

Our understanding of the complex, transcriptional feedback loops in the circadian clock mechanism has depended upon quantitative, timeseries data from disparate sources. We measure clock gene RNA … profiles in Arabidopsis thaliana seedlings, grown with or without exogenous sucrose, or in soil-grown plants and in wild-type and mutant backgrounds. The RNA profiles were strikingly robust across the experimental conditions, so current mathematical models are likely to be broadly applicable in leaf tissue. In addition to providing reference data, unexpected behaviours included co-expression of PRR9 and ELF4, and regulation of PRR5 by GI. Absolute RNA quantification revealed low levels of PRR9 transcripts (peak approx. 50 copies cell(-1)) compared with other clock genes, and threefold higher levels of LHY RNA (more than 1500 copies cell(-1)) than of its close relative CCA1. The data are disseminated from BioDare, an online repository for focused timeseries data, which is expected to benefit mechanistic modelling. One data subset successfully constrained clock gene expression in a complex model, using publicly available software on parallel computers, without expert tuning or programming. We outline the empirical and mathematical justification for data aggregation in understanding highly interconnected, dynamic networks such as the clock, and the observed design constraints on the resources required to make this approach widely accessible.

Authors: A. Flis, A. P. Fernandez, T. Zielinski, V. Mengin, R. Sulpice, K. Stratford, A. Hume, A. Pokhilko, M. M. Southern, D. D. Seaton, H. G. McWatters, M. Stitt, K. J. Halliday, A. J. Millar

Date Published: 16th Oct 2015

Publication Type: Not specified

The circadian clock regulates the photoperiodic response of hypocotyl elongation through a coincidence mechanism in Arabidopsis thaliana

Abstract (Expand)

The plant circadian clock generates rhythms with a period close to 24 h, and it controls a wide range of physiological and developmental oscillations in habitats under natural light/dark cycles. Among … clock-controlled developmental events, the best characterized is the photoperiodic control of flowering time in Arabidopsis thaliana. Recently, it was also reported that the clock regulates a daily and rhythmic elongation of hypocotyls. Here, we report that the promotion of hypocotyl elongation is in fact dependent on changes in photoperiods in such a way that an accelerated hypocotyl elongation occurs especially under short-day conditions. In this regard, we provide genetic evidence to show that the circadian clock regulates the photoperiodic (or seasonal) elongation of hypocotyls by modulating the expression profiles of the PIF4 and PIF5 genes encoding phytochrome-interacting bHLH (basic helix-loop-helix) factors, in such a manner that certain short-day conditions are necessary to enhance the expression of these genes during the night-time. In other words, long-day conditions are insufficient to open the clock-gate for triggering the expression of PIF4 and PIF5 during the night-time. Based on these and other results, the photoperiodic control of hypocotyl elongation is best explained by the accumulation of PIF4 and PIF5 during the night-time of short days, due to coincidence between the internal (circadian rhythm) and external (photoperiod) time cues. This mechanism is a mirror image of the photoperiod-dependent promotion of flowering in that plants should experience long-day conditions to initiate flowering promptly. Both of these clock-mediated coincidence mechanisms may coordinately confer ecological fitness to plants growing in natural habitats with varied photoperiods.

Authors: Y. Niwa, T. Yamashino, T. Mizuno

Date Published: 24th Feb 2009

Publication Type: Not specified

Arabidopsis clock-associated pseudo-response regulators PRR9, PRR7 and PRR5 coordinately and positively regulate flowering time through the canonical CONSTANS-dependent photoperiodic pathway

Abstract (Expand)

Photoperiodism allows organisms to measure daylength, or external photoperiod, and to anticipate coming seasons. Daylength measurement requires the integration of light signal and temporal information … by the circadian clock. In the long-day plant Arabidopsis thaliana, CONSTANS (CO) plays a crucial role in integrating the circadian rhythm and environmental light signals into the photoperiodic flowering pathway. Nevertheless, the molecular mechanism by which the circadian clock modulates the cyclic expression profile of CO is poorly understood. Here, we first showed that the clock-associated genes PSEUDO-RESPONSE REGULATOR (PRR) PRR9, PRR7 and PRR5 are involved in activation of CO expression during the daytime. Then, extensive genetic studies using CIRCADIAN CLOCK-ASSOCIATED1 (CCA1)/LATE ELONGATED HYPOCOTYL (LHY) double mutants (cca1/lhy) and prr7/prr5 were conducted. The results suggested that PRR genes act coordinately in a manner parallel with and antagonistic to CCA/LHY, upstream of the canonical CO-FLOWERING LOCUS T (FT) photoperiodic flowering pathway. Finally, we provided evidence to propose a model, in which CCA1/LHY repress CO through GIGANTEA (GI), while PRR9, PRR7 and PRR5 activate CO predominantly by repressing CYCLING DOF FACTOR1 (CDF1) encoding a DNA-binding transcriptional repressor.

Authors: N. Nakamichi, M. Kita, K. Niinuma, S. Ito, T. Yamashino, T. Mizoguchi, T. Mizuno

Date Published: 17th May 2007

Publication Type: Not specified

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