Smurfit Institute of Genetics, University of Dublin, Trinity College, Dublin, Ireland.
PLoS One. 2013;8(1):e52581. doi: 10.1371/journal.pone.0052581. Epub 2013 Jan 2.
Physical interactions between proteins mediate a variety of biological functions, including signal transduction, physical structuring of the cell and regulation. While extensive catalogs of such interactions are known from model organisms, their evolutionary histories are difficult to study given the lack of interaction data from phylogenetic outgroups. Using phylogenomic approaches, we infer a upper bound on the time of origin for a large set of human protein-protein interactions, showing that most such interactions appear relatively ancient, dating no later than the radiation of placental mammals. By analyzing paired alignments of orthologous and putatively interacting protein-coding genes from eight mammals, we find evidence for weak but significant co-evolution, as measured by relative selective constraint, between pairs of genes with interacting proteins. However, we find no strong evidence for shared instances of directional selection within an interacting pair. Finally, we use a network approach to show that the distribution of selective constraint across the protein interaction network is non-random, with a clear tendency for interacting proteins to share similar selective constraints. Collectively, the results suggest that, on the whole, protein interactions in mammals are under selective constraint, presumably due to their functional roles.
蛋白质之间的物理相互作用介导了多种生物学功能，包括信号转导、细胞的物理结构和调节。虽然从模式生物中已经知道了大量这样的相互作用，但由于缺乏来自系统发育外群的相互作用数据，因此很难研究它们的进化历史。我们使用系统基因组学方法推断了一组人类蛋白质-蛋白质相互作用的起源时间上限，结果表明，大多数这样的相互作用都比较古老，其起源时间不晚于胎盘哺乳动物的辐射时期。通过分析来自 8 种哺乳动物的同源和推测相互作用的蛋白质编码基因的成对比对，我们发现了相对选择性约束（measured by relative selective constraint）在具有相互作用蛋白的基因对之间存在微弱但显著的共同进化的证据。然而，我们没有发现相互作用对中存在共同的定向选择的有力证据。最后，我们使用网络方法表明，选择性约束在蛋白质相互作用网络中的分布是非随机的，相互作用的蛋白质具有相似的选择性约束的趋势非常明显。总的来说，这些结果表明，哺乳动物中的蛋白质相互作用受到选择性约束，这可能是由于它们的功能作用。
