The origins of the evolutionary signal used to predict protein-protein interactions.

The origins of the evolutionary signal used to predict protein-protein interactions.
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DOI:
10.1186/1471-2148-12-238
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发表时间:
2012-12-06
影响因子:
3.4
通讯作者:
Lovell SC
Lovell SC
中科院分区:
生物学2区
文献类型:
--
作者:
Swapna LS;Srinivasan N;Robertson DL;Lovell SC

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蛋白质序列比对对之间遗传距离的相关性已被用来推断蛋白质-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质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明显发生(特别是在结合界面和邻域中),但许多其他因素有助于序列进化的相关速率。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,因此可以预期,无论它们是否相互作用,它们的系统发育树都会存在拓扑相似性。由于这个原因,底层的物种树经常被修正。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括共同的进化历史;在这里我们检验这个假设。为了确定引起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。我们使用一系列来自酿酒酵母的相互作用和非相互作用蛋白质的数据集。我们发现相互作用蛋白质之间的相关进化信号主要是共享进化速率的结果,而不是树拓扑的相似性,与进化分歧无关。由于相互作用的蛋白质不具有比非相互作用蛋白质的对照组更相似的树拓扑,因此共同进化很可能对观察到的相关性(如果有的话)没有太大贡献。
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.
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