Multifunctionality and robustness trade-offs in model genetic circuits
Multifunctionality and robustness trade-offs in model genetic circuits
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DOI：
10.1529/biophysj.107.114348
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发表时间：
2008-04-15
影响因子：
3.4
通讯作者：
Wagner, Andreas
中科院分区：
文献类型：
--
作者：
Martin, Olivier C.;Wagner, Andreas
大多数细胞系统，从大分子到遗传网络，都具有不止一种功能。涉及网络的例子包括由同源异型框（Hox）基因和果蝇分节基因形成的转录调控回路，它们在发育的早期和后期事件中都起作用。执行多种功能的需求是否会严重限制网络结构？这是否意味着功能之间存在稳健性的权衡？也就是说，如果一种功能对突变具有高度的稳健性，那么其他功能是否高度敏感，反之亦然？现有的证据很少能说明这些问题。我们用一个转录调控网络的通用模型来解决这些问题。我们表明，要求一个调控网络执行额外的功能会以指数方式限制允许的网络结构的数量。然而，一种功能对调控突变的稳健性与其他功能的稳健性不相关或呈弱正相关。这意味着在我们所研究的系统中通常不会出现稳健性的权衡。只要有许多可供选择的网络结构，且每个结构都能实现所有必需的功能，多种功能就可能通过渐进的达尔文式进化获得高度的稳健性。
Most cellular systems, from macromolecules to genetic networks, have more than one function. Examples involving networks include the transcriptional regulation circuits formed by Hox genes and the Drosophila segmentation genes, which function in both early and later developmental events. Does the need to carry out more than one function severely constrain network architecture? Does it imply robustness trade-offs among functions? That is, if one function is highly robust to mutations, are other functions highly sensitive, and vice versa? Little available evidence speaks to these questions. We address them with a general model of transcriptional regulation networks. We show that requiring a regulatory network to carry out additional functions constrains the number of permissible network architectures exponentially. However, robustness of one function to regulatory mutations is uncorrelated or weakly positively correlated to robustness of other functions. This means that robustness trade-offs generally do not arise in the systems we study. As long as there are many alternative network structures, each of which can fulfill all required functions, multiple functions may acquire high robustness through gradual Darwinian evolution.