Codon-substitution models for heterogeneous selection pressure at amino acid sites.
Codon-substitution models for heterogeneous selection pressure at amino acid sites.
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发表时间：
2000-04
期刊：
影响因子：
3.3
通讯作者：
Ziheng Yang;R. Nielsen;N. Goldman;Anne-Mette Krabbe Pedersen
中科院分区：
文献类型：
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作者：
Ziheng Yang;R. Nielsen;N. Goldman;Anne-Mette Krabbe Pedersen
同义（沉默）和非同义（氨基酸改变）突变的相对固定率的比较，为理解分子序列进化的机制提供了一种手段。非同义/同义比率（ω = d（N）d（S））是蛋白质水平上选择压力的重要指标，ω = 1意味着中性突变，ω 1使正选择多样化。蛋白质中的氨基酸位点预期处于不同的选择压力下，并且具有不同的潜在ω比。我们开发的模型，占异构欧米茄氨基酸位点之间的比例，并将其应用于蛋白质编码的DNA序列的系统发育分析。这些模型对于适应性分子进化的检验和多样性选择下氨基酸位点的识别是有用的。从核，线粒体和病毒基因组的基因的十个数据集进行分析，以估计欧米茄网站之间的分布。在所有的数据集分析，选择性压力表示的Ω比被发现是高度异构的网站之间。先前未被怀疑的达尔文选择在几个基因中被检测到，其中跨位点的平均ω比为1。经历正选择的基因包括来自脊椎动物的β-珠蛋白基因、来自人科动物的线粒体蛋白编码基因、来自人类流感病毒A的血凝素（HA）基因以及HIV-1 env、vif和pol基因。测试的存在下，积极选择的网站和他们随后的识别出现相当强大的特定分布形式假设为欧米茄，可以实现使用任何几个模型，我们实现。然而，我们遇到的困难，估计精确分布的欧米茄网站之间的真实的数据集。
Comparison of relative fixation rates of synonymous (silent) and nonsynonymous (amino acid-altering) mutations provides a means for understanding the mechanisms of molecular sequence evolution. The nonsynonymous/synonymous rate ratio (omega = d(N)d(S)) is an important indicator of selective pressure at the protein level, with omega = 1 meaning neutral mutations, omega 1 diversifying positive selection. Amino acid sites in a protein are expected to be under different selective pressures and have different underlying omega ratios. We develop models that account for heterogeneous omega ratios among amino acid sites and apply them to phylogenetic analyses of protein-coding DNA sequences. These models are useful for testing for adaptive molecular evolution and identifying amino acid sites under diversifying selection. Ten data sets of genes from nuclear, mitochondrial, and viral genomes are analyzed to estimate the distributions of omega among sites. In all data sets analyzed, the selective pressure indicated by the omega ratio is found to be highly heterogeneous among sites. Previously unsuspected Darwinian selection is detected in several genes in which the average omega ratio across sites is 1. Genes undergoing positive selection include the beta-globin gene from vertebrates, mitochondrial protein-coding genes from hominoids, the hemagglutinin (HA) gene from human influenza virus A, and HIV-1 env, vif, and pol genes. Tests for the presence of positively selected sites and their subsequent identification appear quite robust to the specific distributional form assumed for omega and can be achieved using any of several models we implement. However, we encountered difficulties in estimating the precise distribution of omega among sites from real data sets.