Department of Bioengineering, McGill University, Montreal, Quebec H3C 0C3, Canada.
Institute for Research in Immunology and Cancer, University of Montreal, Montreal, Quebec H3C 3J7, Canada.
Curr Opin Struct Biol. 2018 Jun;50:42-48. doi: 10.1016/j.sbi.2017.10.012. Epub 2017 Nov 5.
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 ∼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.
我们强调了最近在蛋白质-蛋白质相互作用（PPI）网络（“互作组”）的全基因组研究中获得的新进化见解。虽然大多数 PPI 是由单个序列区域介导的，促进或抑制相互作用，但许多 PPI 是由多个序列区域协同作用介导的。大多数 PPI 执行重要的功能，这些功能由负选择维持：我们估计，在受到干扰时，人类互作组中只有不到∼10%是有效的中性（即“垃圾”PPI），其余的在受到干扰时是有害的；界面位点的进化速度比其他位点慢；许多保守的 PPI 在界面上表现出共同进化的特征；PPI 的进化速度比蛋白质序列慢。与此同时，许多 PPI 在进化过程中进行了重新布线，以适应特定谱系。最后，伴侣蛋白和宿主-病原体互作组受不同的进化原则支配。
