National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20894, USA.
Nat Commun. 2016 Nov 18;7:13570. doi: 10.1038/ncomms13570.
Protein repeats are considered hotspots of protein evolution, associated with acquisition of new functions and novel phenotypic traits, including disease. Paradoxically, however, repeats are often strongly conserved through long spans of evolution. To resolve this conundrum, it is necessary to directly compare paralogous (horizontal) evolution of repeats within proteins with their orthologous (vertical) evolution through speciation. Here we develop a rigorous methodology to identify highly periodic repeats with significant sequence similarity, for which evolutionary rates and selection (dN/dS) can be estimated, and systematically characterize their evolution. We show that horizontal evolution of repeats is markedly accelerated compared with their divergence from orthologues in closely related species. This observation is universal across the diversity of life forms and implies a biphasic evolutionary regime whereby new copies experience rapid functional divergence under combined effects of strongly relaxed purifying selection and positive selection, followed by fixation and conservation of each individual repeat.
蛋白质重复被认为是蛋白质进化的热点，与获得新功能和新的表型特征有关，包括疾病。然而，具有讽刺意味的是，重复在很长的进化过程中经常被强烈保守。为了解决这个难题，有必要直接比较蛋白质中重复的旁系（水平）进化与其通过物种形成的直系（垂直）进化。在这里，我们开发了一种严格的方法来识别具有显著序列相似性的高度周期性重复，为此可以估计进化速率和选择（dN/dS），并系统地描述它们的进化。我们表明，与它们在亲缘关系密切的物种中的同源物分化相比，重复的水平进化明显加快。这一观察结果在生命形式的多样性中是普遍存在的，这意味着存在一个双相进化状态，即新的副本在强烈放松的净化选择和正选择的共同作用下经历快速的功能分化，然后每个单独的副本固定和保守。
