Biological role of noise encoded in a genetic network motif
Biological role of noise encoded in a genetic network motif
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DOI：
10.1073/pnas.1003975107
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发表时间：
2010-07-27
影响因子：
11.1
通讯作者：
Suel, Gurol M.
中科院分区：
文献类型：
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作者：
Kittisopikul, Mark;Suel, Gurol M.
调节不同细胞过程的基因回路在其相互作用的连接模式（结构）以及对随机波动（噪声）的敏感性方面可能存在差异。然而，回路结构和噪声之间的联系是否具有生物学重要性仍然知之甚少。为了研究这个问题，我们对前馈环（FFL）基序的所有可能回路结构进行了基因表达噪声的计算研究。结果显示，根据其开启（受刺激）或关闭（未受刺激）稳态是否表现出噪声，FFL结构可分为两类。为了探究这种噪声行为差异的生物学重要性，我们分析了大肠杆菌中858个有记录的FFL，它们被分为39个功能类别。发现大多数FFL调节两个功能子类。有趣的是，这两个功能类别与具有相反噪声行为的FFL相关联。这种相反的噪声偏好揭示了两种基于噪声的策略来应对环境限制，即细胞反应随机地启动或终止，以允许对不同状态进行概率性采样。因此，FFL可能因其结构相关的噪声行为而被选择，这揭示了编码在基因回路结构中的噪声的生物学作用。
Genetic circuits that regulate distinct cellular processes can differ in their wiring pattern of interactions (architecture) and susceptibility to stochastic fluctuations (noise). Whether the link between circuit architecture and noise is of biological importance remains, however, poorly understood. To investigate this problem, we performed a computational study of gene expression noise for all possible circuit architectures of feed-forward loop (FFL) motifs. Results revealed that FFL architectures fall into two categories depending on whether their ON (stimulated) or OFF (unstimulated) steady states exhibit noise. To explore the biological importance of this difference in noise behavior, we analyzed 858 documented FFLs in Escherichia coli that were divided into 39 functional categories. The majority of FFLs were found to regulate two subsets of functional categories. Interestingly, these two functional categories associated with FFLs of opposite noise behaviors. This opposite noise preference revealed two noise-based strategies to cope with environmental constraints where cellular responses are either initiated or terminated stochastically to allow probabilistic sampling of alternative states. FFLs may thus be selected for their architecture-dependent noise behavior, revealing a biological role for noise that is encoded in gene circuit architectures.