Kann Maricel G, Shoemaker Benjamin A, Panchenko Anna R, Przytycka Teresa M
Department of Biological Sciences, University of Maryland, Baltimore County, MD 21250, USA.
J Mol Biol. 2009 Jan 9;385(1):91-8. doi: 10.1016/j.jmb.2008.09.078. Epub 2008 Oct 9.
It has been observed that the evolutionary distances of interacting proteins often display a higher level of similarity than those of noninteracting proteins. This finding indicates that interacting proteins are subject to common evolutionary constraints and constitutes the basis of a method to predict protein interactions known as mirrortree. It has been difficult, however, to identify the direct cause of the observed similarities between evolutionary trees. One possible explanation is the existence of compensatory mutations between partners' binding sites to maintain proper binding. This explanation, though, has been recently challenged, and it has been suggested that the signal of correlated evolution uncovered by the mirrortree method is unrelated to any correlated evolution between binding sites. We examine the contribution of binding sites to the correlation between evolutionary trees of interacting domains. We show that binding neighborhoods of interacting proteins have, on average, higher coevolutionary signal compared with the regions outside binding sites; however, when the binding neighborhood is removed, the remaining domain sequence still contains some coevolutionary signal. In conclusion, the correlation between evolutionary trees of interacting domains cannot exclusively be attributed to the correlated evolution of the binding sites or to common evolutionary pressure exerted on the whole protein domain sequence, each of which contributes to the signal measured by the mirrortree approach.
据观察，相互作用蛋白的进化距离通常比非相互作用蛋白的进化距离表现出更高的相似性水平。这一发现表明，相互作用蛋白受到共同的进化限制，构成了一种预测蛋白相互作用的方法——镜像树法的基础。然而，很难确定进化树之间观察到的相似性的直接原因。一种可能的解释是，伙伴结合位点之间存在补偿性突变以维持适当的结合。不过，这种解释最近受到了挑战，有人提出镜像树法揭示的协同进化信号与结合位点之间的任何协同进化无关。我们研究了结合位点对相互作用结构域进化树之间相关性的贡献。我们表明，与结合位点之外的区域相比，相互作用蛋白的结合邻域平均具有更高的协同进化信号；然而，当去除结合邻域时，剩余的结构域序列仍包含一些协同进化信号。总之，相互作用结构域进化树之间的相关性不能完全归因于结合位点的协同进化或施加于整个蛋白结构域序列的共同进化压力，这两者都对镜像树方法测量的信号有贡献。
