Modeling Protein Evolution with Several Amino Acid Replacement Matrices Depending on Site Rates
Modeling Protein Evolution with Several Amino Acid Replacement Matrices Depending on Site Rates
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DOI：
10.1093/molbev/mss112
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发表时间：
2012-10-01
影响因子：
10.7
通讯作者：
Gascuel, Olivier
中科院分区：
文献类型：
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作者：
Le, Si Quang;Cuong Cao Dang;Gascuel, Olivier
大多数蛋白质替代模型使用单个氨基酸替代矩阵来总结氨基酸的生化性质。然而，网站的演变是高度异质性，并取决于许多因素影响的替代模式。在本文中，我们研究了不同的替代矩阵的使用不同的网站的进化速率。事实上，进化速率的变异性对应于一个最明显的异质性因素之间的网站，并没有理由假设，无论进化速率的替代模式保持不变。我们首先介绍LG4M，它由四个矩阵组成，每个矩阵对应于一个离散伽马速率类别（四个）。这些矩阵的氨基酸平衡分布和可交换性不同，这与标准伽玛模型相反，其中只有全局速率在一个类别与另一个类别之间存在差异。接下来，我们介绍LG4X，它也使用了四种不同的矩阵，但将伽马分布放在一边，并遵循站点速率的分布自由方案。所有这些矩阵估计从一个非常大的比对数据库，我们的两个模型进行了测试，使用大样本的独立比对。对所得矩阵和模型的详细分析显示了氨基酸取代的复杂性以及灵活模型如LG4M和LG4X的优势。这两种模型的性能都明显优于单矩阵模型，为大多数数据集提供了数十到数百个对数似然单位的增益。与LG4M相比，LG4X获得了可观的收益，这要归功于其网站费率的免费分发计划。由于LG4M和LG4X显示了这些优势，但需要相同的内存空间，并且与标准模型的运行时间相当，因此我们认为LG4M和LG4X是单个替换矩阵的相关替代品。我们的模型、数据和软件可从http://www.atgc-montpellier.fr/models/lg4x获得。
Most protein substitution models use a single amino acid replacement matrix summarizing the biochemical properties of amino acids. However, site evolution is highly heterogeneous and depends on many factors that influence the substitution patterns. In this paper, we investigate the use of different substitution matrices for different site evolutionary rates. Indeed, the variability of evolutionary rates corresponds to one of the most apparent heterogeneity factors among sites, and there is no reason to assume that the substitution patterns remain identical regardless of the evolutionary rate. We first introduce LG4M, which is composed of four matrices, each corresponding to one discrete gamma rate category (of four). These matrices differ in their amino acid equilibrium distributions and in their exchangeabilities, contrary to the standard gamma model where only the global rate differs from one category to another. Next, we present LG4X, which also uses four different matrices, but leaves aside the gamma distribution and follows a distribution-free scheme for the site rates. All these matrices are estimated from a very large alignment database, and our two models are tested using a large sample of independent alignments. Detailed analysis of resulting matrices and models shows the complexity of amino acid substitutions and the advantage of flexible models such as LG4M and LG4X. Both significantly outperform single-matrix models, providing gains of dozens to hundreds of log-likelihood units for most data sets. LG4X obtains substantial gains compared with LG4M, thanks to its distribution-free scheme for site rates. Since LG4M and LG4X display such advantages but require the same memory space and have comparable running times to standard models, we believe that LG4M and LG4X are relevant alternatives to single replacement matrices. Our models, data, and software are available from http://www.atgc-montpellier.fr/models/lg4x.