Modeling the site-specific variation of selection patterns along lineages
Modeling the site-specific variation of selection patterns along lineages
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DOI：
10.1073/pnas.0402177101
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发表时间：
2004-08-31
影响因子：
11.1
通讯作者：
Huelsenbeck, JP
中科院分区：
文献类型：
--
作者：
Guindon, S;Rodrigo, AG;Huelsenbeck, JP
与中性预期相比，非同义替换多于同义替换，揭示了蛋白质编码DNA序列中积极达尔文选择的明确足迹。分析非同义和同义替换模式的方法通常依赖于随机模型，其中选择机制可能在序列中变化，但在任何氨基酸位置的谱系中保持不变。尽管一些工作已经放宽了选择模式随时间保持不变的限制，但没有模型提供一个强有力的统计框架来处理在进化过程中单个地点的选择过程之间的切换。本文描述了一种方法，该方法允许特定位点的选择过程沿着系统发育树的谱系变化。利用极大似然法估计了密码子替换切换模型的参数。对八个HIV-1环境同源序列数据集的分析表明，该模型比不考虑单个位点系统发育中选择模式之间切换的模型提供了更好的数据拟合。我们还提供了强有力的证据，表明当选择制度的位点特异性变化被忽略时，选择的强度和发生频率可能无法准确估计。
The unambiguous footprint of positive Darwinian selection in protein-coding DNA sequences is revealed by an excess of nonsynonymous substitutions over synonymous substitutions compared with the neutral expectation. Methods for analyzing the patterns of nonsynonymous and synonymous substitutions usually rely on stochastic models in which the selection regime may vary across the sequence but remains constant across lineages for any amino acid position. Despite some work that has relaxed the constraint that selection patterns remain constant over time, no model provides a strong statistical framework to deal with switches between selection processes at individual sites during the course of evolution. This paper describes an approach that allows the site-specific selection process to vary along lineages of a phylogenetic tree. The parameters of the switching model of codon substitution are estimated by using maximum likelihood. The analysis of eight HIV-1 env homologous sequence data sets shows that this model provides a significantly better fit to the data than one that does not take into account switches between selection patterns in the phylogeny at individual sites. We also provide strong evidence that the strength and the frequency of occurrence of selection might not be estimated accurately when the site-specific variation of selection regimes is ignored.