Smurfit Institute of Genetics, University of Dublin, Trinity College, Dublin 2, Ireland.
Genome Res. 2012 Dec;22(12):2427-35. doi: 10.1101/gr.131953.111. Epub 2012 Jul 26.
Whole genome duplication (WGD) has made a significant contribution to many eukaryotic genomes including yeast, plants, and vertebrates. Following WGD, some ohnologs (WGD paralogs) remain in the genome arranged in blocks of conserved gene order and content (paralogons). However, the most common outcome is loss of one of the ohnolog pair. It is unclear what factors, if any, govern gene loss from paralogons. Recent studies have reported physical clustering (genetic linkage) of functionally linked (interacting) genes in the human genome and propose a biological significance for the clustering of interacting genes such as coexpression or preservation of epistatic interactions. Here we conduct a novel test of a hypothesis that functionally linked genes in the same paralogon are preferentially retained in cis after WGD. We compare the number of protein-protein interactions (PPIs) between linked singletons within a paralogon (defined as cis-PPIs) with that of PPIs between singletons across paralogon pairs (defined as trans-PPIs). We find that paralogons in which the number of cis-PPIs is greater than that of trans-PPIs are significantly enriched in human and yeast. The trend is similar in plants, but it is difficult to assess statistical significance due to multiple, overlapping WGD events. Interestingly, human singletons participating in cis-PPIs tend to be classified into "response to stimulus." We uncover strong evidence of biased gene loss after WGD, which further supports the hypothesis of biologically significant gene clusters in eukaryotic genomes. These observations give us new insight for understanding the evolution of genome structure and of protein interaction networks.
全基因组复制 (WGD) 为包括酵母、植物和脊椎动物在内的许多真核生物基因组做出了重大贡献。WGD 后，一些同源基因（WGD 旁系同源物）仍保留在基因组中，以保守的基因顺序和内容排列（旁系同源基因簇）。然而，最常见的结果是丢失一对同源基因中的一个。目前尚不清楚是什么因素（如果有的话）导致了旁系同源基因的丢失。最近的研究报告称，在人类基因组中，功能相关（相互作用）的基因存在物理聚类（遗传连锁），并提出了相互作用基因聚类的生物学意义，例如共表达或保持上位性相互作用。在这里，我们对一个假设进行了新的测试，即在 WGD 后，同一旁系同源基因簇中的功能相关基因更倾向于在顺式保留。我们比较了旁系同源基因簇内相连单倍体之间的蛋白质-蛋白质相互作用（PPIs）数量（定义为顺式-PPIs）与单倍体之间的 PPIs 数量（定义为反式-PPIs）。我们发现，顺式-PPIs 数量大于反式-PPIs 的旁系同源基因簇在人类和酵母中显著富集。在植物中也存在类似的趋势，但由于存在多个重叠的 WGD 事件，因此很难评估其统计学意义。有趣的是，参与顺式-PPIs 的人类单倍体倾向于被归类为“对刺激的反应”。我们发现了 WGD 后基因偏向性丢失的有力证据，这进一步支持了真核生物基因组中具有生物学意义的基因簇的假说。这些观察结果为我们理解基因组结构和蛋白质相互作用网络的进化提供了新的见解。
