Complementary approaches to understanding the plant circadian clock
Complementary approaches to understanding the plant circadian clock
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DOI：
10.4204/eptcs.19.1
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发表时间：
2010-01-01
影响因子：
--
通讯作者：
Troein, Carl
中科院分区：
文献类型：
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作者：
Akman, Ozgur E.;Guerriero, Maria Luisa;Troein, Carl
生物钟是一种振荡的遗传网络，帮助生物体适应24小时的昼夜循环。绿藻金黄葡萄球菌的时钟是迄今为止发现的最简单的植物时钟。本文提出了随机过程代数Bio-Pepa中的Ostreorics时钟模型，并将其映射到常微分方程组、随机模拟算法和模型检测等不同的分析技术中。这一系统报道的少量分子测试了微分方程式背后的连续近似的极限。我们研究了连续-确定方法和离散-随机方法之间的差异。随机模拟和模型检验使我们能够对系统行为提出新的假设，例如在恒定光照条件下单细胞中存在自持续振荡。我们研究了如何在模型检验的背景下对黎明和黄昏的时间进行建模，以计算关键生化物种的概率分布如何随时间变化。这些结果表明，在表达高峰时，表达水平的相对变化最小，这使得峰值时间成为最佳的实验时相标记。在这些分析的基础上，我们使用进化系统生物学的方法来研究mRNA降解速度的变化如何影响可能影响适应性的关键蛋白质的阶段。我们探索这个生物钟对其潜在生物化学中的这种潜在突变变化的健壮程度。我们的工作表明，多种方法会导致对时钟的更完整的理解。
Circadian clocks are oscillatory genetic networks that help organisms adapt to the 24-hour day/night cycle. The clock of the green alga Ostreococcus tauri is the simplest plant clock discovered so far. Its many advantages as an experimental system facilitate the testing of computational predictions.We present a model of the Ostreococcus clock in the stochastic process algebra Bio-PEPA and exploit its mapping to different analysis techniques, such as ordinary differential equations, stochastic simulation algorithms and model-checking. The small number of molecules reported for this system tests the limits of the continuous approximation underlying differential equations. We investigate the difference between continuous-deterministic and discrete-stochastic approaches. Stochastic simulation and model-checking allow us to formulate new hypotheses on the system behaviour, such as the presence of self-sustained oscillations in single cells under constant light conditions.We investigate how to model the timing of dawn and dusk in the context of model-checking, which we use to compute how the probability distributions of key biochemical species change over time. These show that the relative variation in expression level is smallest at the time of peak expression, making peak time an optimal experimental phase marker. Building on these analyses, we use approaches from evolutionary systems biology to investigate how changes in the rate of mRNA degradation impacts the phase of a key protein likely to affect fitness. We explore how robust this circadian clock is towards such potential mutational changes in its underlying biochemistry. Our work shows that multiple approaches lead to a more complete understanding of the clock.