Evlampiev Kirill, Isambert Hervé
Physico-chimie Curie, Centre National de la Recherche Scientifique Unité Mixte de Recherche 168, Institut Curie, Section de Recherche, 11 rue P & M Curie, 75005 Paris, France.
Proc Natl Acad Sci U S A. 2008 Jul 22;105(29):9863-8. doi: 10.1073/pnas.0804119105. Epub 2008 Jul 16.
Genomic duplication-divergence processes are the primary source of new protein functions and thereby contribute to the evolutionary expansion of functional molecular networks. Yet, it is still unclear to what extent such duplication-divergence processes also restrict by construction the emerging properties of molecular networks, regardless of any specific cellular functions. We address this question, here, focusing on the evolution of protein-protein interaction (PPI) networks. We solve a general duplication-divergence model, based on the statistically necessary deletions of protein-protein interactions arising from stochastic duplications at various genomic scales, from single-gene to whole-genome duplications. Major evolutionary scenarios are shown to depend on two global parameters only: (i) a protein conservation index (M), which controls the evolutionary history of PPI networks, and (ii) a distinct topology index (M') controlling their resulting structure. We then demonstrate that conserved, nondense networks, which are of prime biological relevance, are also necessarily scale-free by construction, irrespective of any evolutionary variations or fluctuations of the model parameters. It is shown to result from a fundamental linkage between individual protein conservation and network topology under general duplication-divergence evolution. By contrast, we find that conservation of network motifs with two or more proteins cannot be indefinitely preserved under general duplication-divergence evolution (independently from any network rewiring dynamics), in broad agreement with empirical evidence between phylogenetically distant species. All in all, these evolutionary constraints, inherent to duplication-divergence processes, appear to have largely controlled the overall topology and scale-dependent conservation of PPI networks, regardless of any specific biological function.
基因组复制-分化过程是新蛋白质功能的主要来源，从而促进了功能分子网络的进化扩展。然而，目前仍不清楚这种复制-分化过程在多大程度上也通过构建来限制分子网络的新兴特性，而不考虑任何特定的细胞功能。我们在此解决这个问题，重点关注蛋白质-蛋白质相互作用（PPI）网络的进化。我们求解了一个通用的复制-分化模型，该模型基于在从单基因到全基因组复制的各种基因组尺度上随机复制产生的蛋白质-蛋白质相互作用的统计必要删除。主要的进化场景显示仅取决于两个全局参数：（i）一个蛋白质保守指数（M），它控制PPI网络的进化历史，以及（ii）一个独特的拓扑指数（M'），控制其最终结构。然后我们证明，具有主要生物学相关性的保守、非密集网络在构建上也必然是无标度的，而与模型参数的任何进化变化或波动无关。这表明是由一般复制-分化进化下个体蛋白质保守性与网络拓扑之间的基本联系导致的。相比之下，我们发现，在一般复制-分化进化下（独立于任何网络重连动态），具有两个或更多蛋白质的网络基序的保守性不能无限期保留，这与系统发育上距离较远物种之间的经验证据广泛一致。总而言之，这些复制-分化过程固有的进化限制似乎在很大程度上控制了PPI网络的整体拓扑和尺度依赖性保守性，而不考虑任何特定的生物学功能。
