Graph splitting: a graph-based approach for superfamily-scale phylogenetic tree reconstruction

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, ...

蛋白质超家族（protein superfamily）包含亲缘关系较远的蛋白质，这些蛋白质经由漫长的进化历程获得了多样的生物学功能。蛋白质超家族早期演化的系统发育分析是一项关键挑战，因为当蛋白质序列分歧度过高、无法构建具备信息价值的多序列比对时，现有系统发育方法的表现不佳。为此，我们提出了图拆分（Graph Splitting, GS）方法，该方法借助基于图的建模方式，可快速构建蛋白质超家族规模的系统发育树。进化模拟实验表明，当序列分歧度较高时，GS方法能够精准重建系统发育树，且对系统发育推断中的几类核心问题具备鲁棒性，包括类群采样偏倚、进化速率异质性以及长枝吸引现象。将该方法应用于磷酸丙糖异构酶（triosephosphate isomerase, TIM）桶状超家族的实证数据集后，研究结果揭示了蛋白质介导的嘧啶生物合成的快速演化进程，……