A protein superfamily contains distantly related proteins that have acquired diverse biological functions through a long evolutionary history. Phylogenetic analysis of the early evolution of protein superfamilies is a key challenge because existing phylogenetic methods show poor performance when protein sequences are too diverged to construct an informative multiple sequence alignment. Here, we propose the Graph Splitting (GS) method, which rapidly reconstructs a protein superfamily-scale phylogenetic tree using a graph-based approach. Evolutionary simulation showed that the GS method can accurately reconstruct phylogenetic trees and be robust to major problems in phylogenetic estimation, such as biased taxon sampling, heterogeneous evolutionary rates, and long-branch attraction when sequences are substantially diverged. Its application to an empirical dataset of the triosephosphate isomerase (TIM)-barrel superfamily suggests rapid evolution of protein-mediated pyrimidine biosynthesis, likely taking place after the RNA world. Furthermore, the GS method can also substantially improve performance of widely used multiple sequence alignment methods by providing accurate guide trees.

中文翻译：

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图拆分：基于图的超家族规模系统发育树重建方法

蛋白质超家族包含远亲的蛋白质，这些蛋白质在漫长的进化历史中获得了多种生物学功能。蛋白质超家族早期进化的系统发育分析是一个关键挑战，因为当蛋白质序列过于分散而无法构建信息丰富的多序列比对时，现有的系统发育方法表现不佳。在这里，我们提出了图拆分（GS）方法，该方法使用基于图的方法快速重建蛋白质超家族规模的系统发育树。进化模拟表明，GS 方法可以准确地重建系统发育树，并且对系统发育估计中的主要问题具有鲁棒性，例如在序列显着发散时有偏向的分类单元采样、异质进化率和长分支吸引。其应用于磷酸丙糖异构酶 (TIM)-桶超家族的经验数据集表明蛋白质介导的嘧啶生物合成的快速进化，可能发生在 RNA 世界之后。此外，GS 方法还可以通过提供准确的引导树来显着提高广泛使用的多序列比对方法的性能。