US Army Engineer Research and Development Center, 3909 Halls Ferry Road, Vicksburg, Mississippi 39180, USA.
Oak Ridge Institute for Science and Education, Oak Ridge, Tennessee 37830, USA.
Nat Commun. 2017 Jul 10;8:16009. doi: 10.1038/ncomms16009.
Metazoan signalling networks are complex, with extensive crosstalk between pathways. It is unclear what pressures drove the evolution of this architecture. We explore the hypothesis that crosstalk allows different cell types, each expressing a specific subset of signalling proteins, to activate different outputs when faced with the same inputs, responding differently to the same environment. We find that the pressure to generate diversity leads to the evolution of networks with extensive crosstalk. Using available data, we find that human tissues exhibit higher levels of diversity between cell types than networks with random expression patterns or networks with no crosstalk. We also find that crosstalk and differential expression can influence drug activity: no protein has the same impact on two tissues when inhibited. In addition to providing a possible explanation for the evolution of crosstalk, our work indicates that consideration of cellular context will likely be crucial for targeting signalling networks.
后生动物信号网络非常复杂，不同信号通路之间存在广泛的串扰。目前尚不清楚是什么压力导致了这种架构的进化。我们探索了这样一种假设，即串扰允许不同的细胞类型，每个细胞类型都表达特定的信号蛋白亚群，在面对相同的输入时激活不同的输出，从而对相同的环境做出不同的反应。我们发现，产生多样性的压力导致了具有广泛串扰的网络的进化。利用现有数据，我们发现人类组织中细胞类型之间的多样性水平高于随机表达模式的网络或没有串扰的网络。我们还发现串扰和差异表达会影响药物活性：当被抑制时，没有一种蛋白质对两种组织产生相同的影响。除了为串扰的进化提供了一种可能的解释外，我们的工作还表明，考虑细胞环境可能对靶向信号网络至关重要。
