Energy landscape reveals that the budding yeast cell cycle is a robust and adaptive multi-stage process.
Energy landscape reveals that the budding yeast cell cycle is a robust and adaptive multi-stage process.
复制标题
能源景观揭示出芽酵母细胞周期是一个稳健且适应性强的多阶段过程
DOI：
10.1371/journal.pcbi.1004156
复制
发表时间：
2015-03
影响因子：
4.3
通讯作者：
Li T
中科院分区：
文献类型：
--
作者：
Lv C;Li X;Li F;Li T
对于大多数真核生物来说，定量理解噪声影响下细胞周期动力学的鲁棒性、适应性和效率是一个基本但难以回答的问题。使用受内在噪声扰动的简化芽殖酵母细胞周期模型，我们通过基于大偏差理论为所考虑的系统构建能量景观，从能量景观的角度系统地探索这些问题。分析表明，细胞周期轨迹受到周围能量势垒的严格限制，并且沿着该轨迹的景观呈现出大致平坦的形状。我们通过结合系统的非梯度性质来解释系统在这条平坦路径上的演化。此外，我们还说明了这种全局景观如何响应外部信号而变化，观察到当营养充足时可兴奋系统接近极限循环系统时景观的良好转变，以及当 DNA 复制检查点被激活时额外能量井的形成。通过考虑有限体积效应，我们在与细胞周期检查点机制相关的景观中沿着平坦的循环路径发现了额外的凹坑。还讨论了由内在和外在噪音引起的景观之间的差异。我们认为，我们简化模型的这种精细的能量景观结构对于其他细胞周期动力学具有普遍意义，并且所提出的方法可以应用于研究类似的生物系统。
Quantitatively understanding the robustness, adaptivity and efficiency of cell cycle dynamics under the influence of noise is a fundamental but difficult question to answer for most eukaryotic organisms. Using a simplified budding yeast cell cycle model perturbed by intrinsic noise, we systematically explore these issues from an energy landscape point of view by constructing an energy landscape for the considered system based on large deviation theory. Analysis shows that the cell cycle trajectory is sharply confined by the ambient energy barrier, and the landscape along this trajectory exhibits a generally flat shape. We explain the evolution of the system on this flat path by incorporating its non-gradient nature. Furthermore, we illustrate how this global landscape changes in response to external signals, observing a nice transformation of the landscapes as the excitable system approaches a limit cycle system when nutrients are sufficient, as well as the formation of additional energy wells when the DNA replication checkpoint is activated. By taking into account the finite volume effect, we find additional pits along the flat cycle path in the landscape associated with the checkpoint mechanism of the cell cycle. The difference between the landscapes induced by intrinsic and extrinsic noise is also discussed. In our opinion, this meticulous structure of the energy landscape for our simplified model is of general interest to other cell cycle dynamics, and the proposed methods can be applied to study similar biological systems.
登录
查看更多内容
影响因子：
21.3
作者：
Novak, Bela;Tyson, John J.;Csikasz-Nagy, Attila
通讯作者：
Csikasz-Nagy, Attila
影响因子：
64.5
作者：
Ferrell, James E., Jr.;Tsai, Tony Yu-Chen;Yang, Qiong
通讯作者：
Yang, Qiong
影响因子：
7.5
作者：
Friedel, Anna M.;Pike, Brietta L.;Gasser, Susan M.
通讯作者：
Gasser, Susan M.
影响因子：
64.8
作者：
Skotheim, Jan M.;Di Talia, Stefano;Siggia, Eric D.;Cross, Frederick R.
通讯作者：
Cross, Frederick R.
DOI：
10.1126/science.1216379
发表时间：
2012-04-13
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Munsky B;Neuert G;van Oudenaarden A
通讯作者：
van Oudenaarden A