An empirical codon model for protein sequence evolution
An empirical codon model for protein sequence evolution
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DOI：
10.1093/molbev/msm064
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发表时间：
2007-07-01
影响因子：
10.7
通讯作者：
Goldman, Nick
中科院分区：
文献类型：
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作者：
Kosiol, Carolin;Holmes, Ian;Goldman, Nick
过去，人们考虑用两种马尔可夫模型来描述蛋白质序列的进化。密码子水平的模型是基于机理的，具有少量参数，旨在考虑诸如转换 - 颠换偏好、密码子频率偏好以及同义 - 非同义氨基酸替换偏好等特征。氨基酸模型是基于经验的，试图总结在大量数据中观察到的替换模式，而没有明确考虑影响蛋白质进化的不同因素。我们估算出了第一个经验性密码子模型（ECM）。先前的密码子模型假定蛋白质进化仅仅通过连续的单核苷酸替换进行，但我们的结果表明，通过纳入瞬时的双核苷酸和三核苷酸变化，模型的准确性得到了显著提高。我们还发现密码子之间的关联、每个密码子所编码的氨基酸以及氨基酸的物理化学性质是驱动密码子进化过程的主要因素。多核苷酸变化、遗传密码的强大影响以及氨基酸的物理化学性质都没有成为标准机理模型及其关于密码子进化如何进行的观点的一部分。我们已经将ECM用于基于似然性的系统发育分析，并且对其描述蛋白质进化能力的评估表明，它始终优于类似的机理密码子模型。我们指出了我们的ECM的生物学解释以及对选择研究可能产生的影响。
In the past, 2 kinds of Markov models have been considered to describe protein sequence evolution. Codon-level models have been mechanistic with a small number of parameters designed to take into account features, such as transition-transversion bias, codon frequency bias, and synonymous-nonsynonymous amino acid substitution bias. Amino acid models have been empirical, attempting to summarize the replacement patterns observed in large quantities of data and not explicitly considering the distinct factors that shape protein evolution. We have estimated the first empirical codon model (ECM). Previous codon models assume that protein evolution proceeds only by successive single nucleotide substitutions, but our results indicate that model accuracy is significantly improved by incorporating instantaneous doublet and triplet changes. We also find that the affiliations between codons, the amino acid each encodes and the physicochemical properties of the amino acids are main factors driving the process of codon evolution. Neither multiple nucleotide changes nor the strong influence of the genetic code nor amino acids' physicochemical properties form a part of standard mechanistic models and their views of how codon evolution proceeds. We have implemented the ECM for likelihood-based phylogenetic analysis, and an assessment of its ability to describe protein evolution shows that it consistently outperforms comparable mechanistic codon models. We point out the biological interpretation of our ECM and possible consequences for studies of selection.