Likelihood models for detecting positively selected amino acid sites and applications to the HIV-1 envelope gene.
Likelihood models for detecting positively selected amino acid sites and applications to the HIV-1 envelope gene.
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作者：
R. Nielsen;Ziheng Yang
几种基于密码子的蛋白质编码DNA序列进化模型被开发出来，用于解释氨基酸位点之间不同的选择强度。“中性模型”假设了两类位点，其中氨基酸替换要么是中性的，要么是有害的。“正选择模型”假设了一个额外的正选择位点类别，其中非同义替换比同义替换发生的速率更高。该模型还用于确定正选择的目标位点。这些模型应用于HIV-1包膜基因V3区域的数据集，在一个患者感染后的不同年份进行测序。研究结果为氨基酸位点的可变选择强度提供了强有力的支持，中性模型被拒绝，而正选择模型被支持，表明正选择在该区域运行。正向选择位点在V3区和侧翼区均有发现。
Several codon-based models for the evolution of protein-coding DNA sequences are developed that account for varying selection intensity among amino acid sites. The "neutral model" assumes two categories of sites at which amino acid replacements are either neutral or deleterious. The "positive-selection model" assumes an additional category of positively selected sites at which nonsynonymous substitutions occur at a higher rate than synonymous ones. This model is also used to identify target sites for positive selection. The models are applied to a data set of the V3 region of the HIV-1 envelope gene, sequenced at different years after the infection of one patient. The results provide strong support for variable selection intensity among amino acid sites The neutral model is rejected in favor of the positive-selection model, indicating the operation of positive selection in the region. Positively selected sites are found in both the V3 region and the flanking regions.