A combined empirical and mechanistic codon model
A combined empirical and mechanistic codon model
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DOI：
10.1093/molbev/msl175
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发表时间：
2007-02-01
影响因子：
10.7
通讯作者：
Pupko, Tal
中科院分区：
文献类型：
--
作者：
Doron-Faigenboim, Adi;Pupko, Tal
作用于蛋白质的进化选择力通常使用进化密码子模型通过对比同义与非同义取代的速率来推断。最广泛使用的模型是基于理论假设，忽略了不同的氨基酸在其替代率不同的经验观察。在本文中，我们开发了一种通用的方法，允许同化的经验氨基酸置换概率到一个密码子取代矩阵。以这种方式，所得到的密码子模型不仅考虑了转换-颠换偏差和非同义/同义比，而且还考虑了经验氨基酸矩阵中指定的不同氨基酸置换概率。不同的经验氨基酸置换基质，如二级结构特异性基质或细胞器特异性基质（例如，线粒体和叶绿体）可以被并入模型中，使其依赖于环境。使用一组不同的编码DNA序列，我们表明，新的模型更好地适应生物数据相比，无论是机械或经验密码子模型。使用建议的模型，我们进一步分析人类免疫缺陷病毒1型蛋白酶序列从药物治疗的患者，并揭示了积极的选择，已知赋予耐药性的病毒的网站。
The evolutionary selection forces acting on a protein are commonly inferred using evolutionary codon models by contrasting the rate of synonymous to nonsynonymous substitutions. Most widely used models are based on theoretical assumptions and ignore the empirical observation that distinct amino acids differ in their replacement rates. In this paper, we develop a general method that allows assimilation of empirical amino acid replacement probabilities into a codon-substitution matrix. In this way, the resulting codon model takes into account not only the transition-transversion bias and the nonsynonymous/synonymous ratio, but also the different amino acid replacement probabilities as specified in empirical amino acid matrices. Different empirical amino acid replacement matrices, such as secondary structure-specific matrices or organelle-specific matrices (e.g., mitochondria and chloroplasts), can be incorporated into the model, making it context dependent. Using a diverse set of coding DNA sequences, we show that the novel model better fits biological data as compared with either mechanistic or empirical codon models. Using the suggested model, we further analyze human immunodeficiency virus type 1 protease sequences obtained from drug-treated patients and reveal positive selection in sites that are known to confer drug resistance to the virus.