A maximum likelihood method for detecting functional divergence at individual codon sites, with application to gene family evolution
A maximum likelihood method for detecting functional divergence at individual codon sites, with application to gene family evolution
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DOI：
10.1007/s00239-004-2597-8
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发表时间：
2004-07-01
影响因子：
3.9
通讯作者：
Yang, ZH
中科院分区：
文献类型：
--
作者：
Bielawski, JP;Yang, ZH
对现有遗传系统进行调整以适应新的用途被称为遗传协同选择。遗传协同选择的机制一直难以研究，因为难以确定功能上的重要变化。研究蛋白质编码基因中的遗传共选择的一种方法是鉴定那些在遗传共选择事件后经历了选择压力变化的氨基酸位点。在本文中，我们提出了一个最大似然法用于测量分歧选择压力和确定受分歧选择影响的氨基酸位点。该方法基于进化的密码子模型，并使用非同义-同义比率（ω）作为对蛋白质的选择的量度，ω 1、< 1和> 1分别表示中性进化、纯化选择和阳性选择。该模型允许在欧米茄网站之间的变化，与一小部分的网站发展不同的选择压力下。分化选择由进化枝之间的不同Ω指示，例如在基因家族的旁系同源进化枝之间。我们将密码子模型应用于重复，然后是（i）α-珠蛋白和γ-珠蛋白基因和（ii）嗜酸性粒细胞阳离子蛋白（ECP）和嗜酸性粒细胞衍生的神经毒素（EDN）基因的功能分歧。在这两种情况下，似然比检验表明，存在的网站不断变化的不同选择的压力。γ-珠蛋白和γ-珠蛋白的分析结果表明，不同的选择压力可能。是胎儿血红蛋白和2，3-二磷酸甘油酸之间关系减弱的结果。我们建议，经验贝叶斯识别的网站演变不同的选择压力下，结合结构和功能信息，可以提供一个有价值的框架，识别和研究遗传的协同选择机制。新方法的局限性进行了讨论。
The tailoring of existing genetic systems to new uses is called genetic co-option. Mechanisms of genetic co-option have been difficult to study because of difficulties in identifying functionally important changes. One way to study genetic co-option in protein-coding genes is to identify those amino acid sites that have experienced changes in selective pressure following a genetic co-option event. In this paper we present a maximum likelihood method useful for measuring divergent selective pressures and identifying the amino acid sites affected by divergent selection. The method is based on a codon model of evolution and uses the nonsynonymous-to-synonymous rate ratio (omega) as a measure of selection on the protein, with omega 1, < 1, and > 1 indicating neutral evolution, purifying selection, and positive selection, respectively. The model allows variation in omega among sites, with a fraction of sites evolving under divergent selective pressures. Divergent selection is indicated by different omega's between clades, such as between paralogous clades of a gene family. We applied the codon model to duplication followed by functional divergence of (i) the epsilon, and gamma globin genes and (ii) the eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN) genes. In both cases likelihood ratio tests suggested the presence of sites evolving under divergent selective pressures. Results of the epsilon and gamma globin analysis suggested that divergent selective pressures might. be a consequence of a weakened relationship between fetal hemoglobin and 2,3-diphosphoglycerate. We suggest that empirical Bayesian identification of sites evolving under divergent selective pressures, combined with structural and functional information, can provide a valuable framework for identifying and studying mechanisms of genetic co-option. Limitations of the new method are discussed.