Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560 012, India.
BMC Evol Biol. 2012 Dec 6;12:238. doi: 10.1186/1471-2148-12-238.
The correlation of genetic distances between pairs of protein sequence alignments has been used to infer protein-protein interactions. It has been suggested that these correlations are based on the signal of co-evolution between interacting proteins. However, although mutations in different proteins associated with maintaining an interaction clearly occur (particularly in binding interfaces and neighbourhoods), many other factors contribute to correlated rates of sequence evolution. Proteins in the same genome are usually linked by shared evolutionary history and so it would be expected that there would be topological similarities in their phylogenetic trees, whether they are interacting or not. For this reason the underlying species tree is often corrected for. Moreover processes such as expression level, are known to effect evolutionary rates. However, it has been argued that the correlated rates of evolution used to predict protein interaction explicitly includes shared evolutionary history; here we test this hypothesis.
In order to identify the evolutionary mechanisms giving rise to the correlations between interaction proteins, we use phylogenetic methods to distinguish similarities in tree topologies from similarities in genetic distances. We use a range of datasets of interacting and non-interacting proteins from Saccharomyces cerevisiae. We find that the signal of correlated evolution between interacting proteins is predominantly a result of shared evolutionary rates, rather than similarities in tree topology, independent of evolutionary divergence.
Since interacting proteins do not have tree topologies that are more similar than the control group of non-interacting proteins, it is likely that coevolution does not contribute much to, if any, of the observed correlations.
蛋白质序列比对之间的遗传距离的相关性已被用于推断蛋白质-蛋白质相互作用。有人认为，这些相关性是基于相互作用蛋白之间共同进化的信号。然而，尽管与维持相互作用相关的不同蛋白质中的突变确实会发生（特别是在结合界面和邻近区域），但许多其他因素也会导致序列进化的相关性。同一基因组中的蛋白质通常通过共同的进化历史联系在一起，因此无论它们是否相互作用，它们的系统发育树都应该具有拓扑相似性。出于这个原因，通常会对基础种系发生树进行校正。此外，已知表达水平等过程会影响进化速率。然而，有人认为，用于预测蛋白质相互作用的相关进化速率明确包含共同的进化历史；在这里，我们检验了这一假设。
为了确定导致相互作用蛋白之间相关性的进化机制，我们使用系统发育方法来区分树拓扑的相似性和遗传距离的相似性。我们使用来自酿酒酵母的一系列相互作用和非相互作用蛋白数据集。我们发现，相互作用蛋白之间相关进化的信号主要是共同进化率的结果，而不是树拓扑的相似性，与进化分歧无关。
由于相互作用蛋白的树拓扑与其非相互作用蛋白的控制组相比没有更相似，因此共同进化可能对观察到的相关性没有什么贡献，如果有的话。
