Interactome evolution: insights from genome-wide analyses of protein-protein interactions

We highlight new evolutionary insights enabled by recent genome-wide studies on protein-protein interaction (PPI) networks ('interactomes'). While most PPIs are mediated by a single sequence region promoting or inhibiting interactions, many PPIs are mediated by multiple sequence regions acting cooperatively. Most PPIs perform important functions maintained by negative selection: we estimate that less than similar to 10% of the human interactome is effectively neutral upon perturbation (i.e. 'junk' PPIs), and the rest are deleterious upon perturbation; interfacial sites evolve more slowly than other sites; many conserved PPIs show signatures of co-evolution at the interface; PPIs evolve more slowly than protein sequence. At the same time, many PPIs undergo rewiring during evolution for lineage-specific adaptation. Finally, chaperone-protein and host-pathogen interactomes are governed by distinct evolutionary principles.

我们强调由近期对蛋白质 - 蛋白质相互作用（PPI）网络（“相互作用组”）的全基因组研究带来的新的进化见解。虽然大多数PPI是由促进或抑制相互作用的单个序列区域介导的，但许多PPI是由多个协同作用的序列区域介导的。大多数PPI执行由负选择维持的重要功能：我们估计，在扰动时，人类相互作用组中只有不到约10%是实际上中性的（即“无用”的PPI），其余的在扰动时是有害的；界面位点比其他位点进化得更慢；许多保守的PPI在界面处显示出共同进化的特征；PPI比蛋白质序列进化得更慢。同时，许多PPI在进化过程中会因谱系特异性适应而发生重新连接。最后，伴侣蛋白 - 蛋白质和宿主 - 病原体相互作用组受不同的进化原则支配。