Protein evolution with dependence among codons due to tertiary structure
Protein evolution with dependence among codons due to tertiary structure
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DOI：
10.1093/molbev/msg184
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发表时间：
2003-10-01
影响因子：
10.7
通讯作者：
Thorne, JL
中科院分区：
文献类型：
--
作者：
Robinson, DM;Jones, DT;Thorne, JL
考虑了蛋白质进化的马尔可夫模型，该模型放松了密码子之间独立变化的假设。有了这个相对现实的框架，一个遗址的进化速度既取决于遗址的状态，也取决于周围遗址的状态。通过允许位点间相对普遍的依赖结构，进化模型可以反映三级结构的属性。为了量化蛋白质结构对蛋白质进化的影响，我们用一个包含溶剂可及性和氨基酸残基之间成对相互作用影响的进化模型分析了蛋白质编码DNA序列对。通过明确地考虑非同义取代率和蛋白质结构之间的关系，这种方法可以精确地检测和表征正选择。对模拟序列对的分析表明，该进化模型可以很好地估计参数。对溶菌酶c和膜联蛋白V序列对的分析得出了生物学上合理的结果，即当氨基酸替换导致能量上有利的蛋白质时，氨基酸替换率高于使蛋白质不稳定时的氨基酸替换率。虽然这里的重点是与蛋白质结构相关的密码子之间的进化依赖性，但统计方法是相当普遍的，可以应用于进化依赖性的各种情况，其中序列适应度的替代品可以测量或建模。
Markovian models of protein evolution that relax the assumption of independent change among codons are considered. With this comparatively realistic framework, an evolutionary rate at a site can depend both on the state of the site and on the states of surrounding sites. By allowing a relatively general dependence structure among sites, models of evolution can reflect attributes of tertiary structure. To quantify the impact of protein structure on protein evolution, we analyze protein-coding DNA sequence pairs with an evolutionary model that incorporates effects of solvent accessibility and pairwise interactions among amino acid residues. By explicitly considering the relationship between nonsynonymous substitution rates and protein structure, this approach can lead to refined detection and characterization of positive selection. Analyses of simulated sequence pairs indicate that parameters in this evolutionary model can be well estimated. Analyses of lysozyme c and annexin V sequence pairs yield the biologically reasonable result that amino acid replacement rates are higher when the replacements lead to energetically favorable proteins than when they destabilize the proteins. Although the focus here is evolutionary dependence among codons that is associated with protein structure, the statistical approach is quite general and could be applied to diverse cases of evolutionary dependence where surrogates for sequence fitness can be measured or modeled.