Kong Hongzhi, Leebens-Mack Jim, Ni Weimin, dePamphilis Claude W, Ma Hong
Laboratory of Systematic and Evolutionary Botany, Institute of Botany, The Chinese Academy of Sciences, Beijing, China.
Mol Biol Evol. 2004 Jan;21(1):117-28. doi: 10.1093/molbev/msh001. Epub 2003 Oct 31.
Skp1 (S-phase kinase-associated protein 1) is a core component of SCF ubiquitin ligases and mediates protein degradation, thereby regulating eukaryotic fundamental processes such as cell cycle progression, transcriptional regulation, and signal transduction. Among the four components of the SCF complexes, Rbx1 and Cullin form a core catalytic complex, an F-box protein acts as a receptor for target proteins, and Skp1 is an adaptor between one of the variable F-box proteins and Cullin. Whereas protists, fungi, and some vertebrates have a single SKP1 gene, many animal and plant species possess multiple SKP1 homologs. It has been shown that the same Skp1 homolog can interact with two or more F-box proteins, and different Skp1 homologs from the same species sometimes can interact with the same F-box protein. In this paper, we demonstrate that multiple Skp1 homologs from the same species have evolved at highly heterogeneous rates. Parametric bootstrap analyses suggested that the differences in evolutionary rate are so large that true phylogenies were not recoverable from the full data set. Only when the original data set were partitioned into sets of genes with slow, medium, and rapid rates of evolution and analyzed separately, better-resolved relationships were observed. The slowly evolving Skp1 homologs, which are relatively highly conserved in sequence and expressed widely and/or at high levels, usually have very low d(N)/d(S) values, suggesting that they have evolved under functional constraint and serve the most fundamental function(s). On the other hand, the rapidly evolving members are structurally more diverse and usually have limited expression patterns and higher d(N)/d(S) values, suggesting that they may have evolved under relaxed or altered constraint, or even under positive selection. Some rapidly evolving members may have lost their original function(s) and/or acquired new function(s) or become pseudogenes, as suggested by their expression patterns, d(N)/d(S) values, and amino acid changes at key positions. In addition, our analyses revealed several monophyletic groups within the SKP1 gene family, one for each of protists, fungi, animals, and plants, as well as nematodes, arthropods, and angiosperms, suggesting that the extant SKP1 genes within each of these eukaryote groups shared only one common ancestor.
Skp1（S期激酶相关蛋白1）是SCF泛素连接酶的核心组成部分，介导蛋白质降解，从而调节真核生物的基本过程，如细胞周期进程、转录调控和信号转导。在SCF复合物的四个组成部分中，Rbx1和Cullin形成核心催化复合物，一个F-box蛋白作为靶蛋白的受体，而Skp1是可变F-box蛋白之一与Cullin之间的衔接蛋白。原生生物、真菌和一些脊椎动物有一个单一的SKP1基因，而许多动植物物种拥有多个SKP1同源物。研究表明，同一个Skp1同源物可以与两个或更多的F-box蛋白相互作用，同一物种的不同Skp1同源物有时也可以与同一个F-box蛋白相互作用。在本文中，我们证明同一物种的多个Skp1同源物以高度异质的速率进化。参数自展分析表明，进化速率的差异非常大，以至于无法从完整的数据集中恢复真实的系统发育。只有当原始数据集被划分为进化速率慢、中、快的基因集并分别进行分析时，才能观察到分辨率更高的关系。进化缓慢的Skp1同源物在序列上相对高度保守，广泛表达和/或高水平表达，通常具有非常低的d(N)/d(S)值，这表明它们在功能限制下进化并发挥最基本的功能。另一方面，快速进化的成员在结构上更加多样化，通常具有有限的表达模式和更高的d(N)/d(S)值，这表明它们可能在放松或改变的限制下进化，甚至在正选择下进化。一些快速进化的成员可能已经失去了它们原来的功能和/或获得了新的功能或成为假基因，这从它们的表达模式、d(N)/d(S)值和关键位置的氨基酸变化可以看出。此外，我们的分析揭示了SKP1基因家族中的几个单系类群，原生生物、真菌、动物和植物各有一个，以及线虫、节肢动物和被子植物，这表明这些真核生物群体中的每个现存SKP1基因都只有一个共同祖先。
