Modeling site heterogeneity with posterior mean site frequency profiles accelerates accurate phylogenomic estimation

Proteins have distinct structural and functional constraints at different sites that lead to site-specific preferences for particular amino acid residues as the sequences evolve. Heterogeneity in the amino acid substitution process between sites is not modeled by commonly used empirical amino acid exchange matrices. Such model misspecification can lead to artefacts in phylogenetic estimation such as long-branch attraction. Although sophisticated site-heterogeneous mixture models have been developed to address this problem in both Bayesian and maximum likelihood (ML) frameworks, their formidable computational time and memory usage severely limits their use in large phylogenomic analyses. Here we propose a posterior mean site frequency (PMSF) method as a rapid and efficient approximation to full empirical profile mixture models for ML analysis. The PMSF approach assigns a conditional mean amino acid frequency profile to each site calculated based on a mixture model fitted to the data usin...蛋白质在不同位点存在独特的结构与功能约束，这使得序列演化过程中，各特定位点对特定氨基酸残基存在位点特异性偏好。当前常用的经验氨基酸替换矩阵并未对位点间氨基酸替换过程的异质性进行建模。此类模型设定误差可能导致系统发育推断中出现人为假象，例如长枝吸引（long-branch attraction）。尽管学界已开发出复杂的位点异质性混合模型，可在贝叶斯与最大似然（ML）框架下解决该问题，但这类模型高昂的计算耗时与内存占用严重限制了其在大规模系统基因组分析中的应用。本文提出一种后验均值位点频率（PMSF）方法，可作为适用于最大似然分析的完整经验谱混合模型的快速高效近似方案。PMSF方法为每个位点分配条件平均氨基酸频率谱，该谱基于从数据中拟合得到的混合模型计算得出……