Munteanu Andreea, Constante Marco, Isalan Mark, Solé Ricard V
ICREA-Complex Systems Lab, Universitat Pompeu Fabra (PRBB-GRIB), Dr Aiguader 88, 08003 Barcelona, Spain.
BMC Syst Biol. 2010 May 17;4:66. doi: 10.1186/1752-0509-4-66.
The ultimate goal of synthetic biology is the conception and construction of genetic circuits that are reliable with respect to their designed function (e.g. oscillators, switches). This task remains still to be attained due to the inherent synergy of the biological building blocks and to an insufficient feedback between experiments and mathematical models. Nevertheless, the progress in these directions has been substantial.
It has been emphasized in the literature that the architecture of a genetic oscillator must include positive (activating) and negative (inhibiting) genetic interactions in order to yield robust oscillations. Our results point out that the oscillatory capacity is not only affected by the interaction polarity but by how it is implemented at promoter level. For a chosen oscillator architecture, we show by means of numerical simulations that the existence or lack of competition between activator and inhibitor at promoter level affects the probability of producing oscillations and also leaves characteristic fingerprints on the associated period/amplitude features.
In comparison with non-competitive binding at promoters, competition drastically reduces the region of the parameters space characterized by oscillatory solutions. Moreover, while competition leads to pulse-like oscillations with long-tail distribution in period and amplitude for various parameters or noisy conditions, the non-competitive scenario shows a characteristic frequency and confined amplitude values. Our study also situates the competition mechanism in the context of existing genetic oscillators, with emphasis on the Atkinson oscillator.
合成生物学的最终目标是构思和构建在设计功能方面可靠的遗传回路（例如振荡器、开关）。由于生物构建模块固有的协同作用以及实验与数学模型之间的反馈不足，这一任务仍有待实现。然而，在这些方向上已经取得了显著进展。
文献中强调，遗传振荡器的架构必须包括正向（激活）和负向（抑制）遗传相互作用，以产生稳健的振荡。我们的结果指出，振荡能力不仅受相互作用极性的影响，还受其在启动子水平上的实现方式的影响。对于选定的振荡器架构，我们通过数值模拟表明，启动子水平上激活剂和抑制剂之间竞争的存在与否会影响产生振荡的概率，并且还会在相关的周期/幅度特征上留下特征指纹。
与启动子处的非竞争性结合相比，竞争极大地减少了以振荡解为特征的参数空间区域。此外，虽然竞争会导致在各种参数或噪声条件下周期和幅度具有长尾分布的脉冲状振荡，但非竞争情况显示出特征频率和受限的幅度值。我们的研究还将竞争机制置于现有遗传振荡器的背景下，重点是阿特金森振荡器。
