Massingham Tim, Goldman Nick
European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, UK.
Genetics. 2005 Mar;169(3):1753-62. doi: 10.1534/genetics.104.032144. Epub 2005 Jan 16.
An excess of nonsynonymous over synonymous substitution at individual amino acid sites is an important indicator that positive selection has affected the evolution of a protein between the extant sequences under study and their most recent common ancestor. Several methods exist to detect the presence, and sometimes location, of positively selected sites in alignments of protein-coding sequences. This article describes the "sitewise likelihood-ratio" (SLR) method for detecting nonneutral evolution, a statistical test that can identify sites that are unusually conserved as well as those that are unusually variable. We show that the SLR method can be more powerful than currently published methods for detecting the location of positive selection, especially in difficult cases where the strength of selection is low. The increase in power is achieved while relaxing assumptions about how the strength of selection varies over sites and without elevated rates of false-positive results that have been reported with some other methods. We also show that the SLR method performs well even under circumstances where the results from some previous methods can be misleading.
在单个氨基酸位点上，非同义替换超过同义替换是一个重要指标，表明正选择影响了所研究的现存序列与其最近共同祖先之间蛋白质的进化。有几种方法可用于检测蛋白质编码序列比对中正向选择位点的存在情况，有时还能确定其位置。本文介绍了用于检测非中性进化的“位点似然比”（SLR）方法，这是一种统计检验，可识别异常保守以及异常可变的位点。我们表明，SLR方法在检测正向选择位置方面可能比目前已发表的方法更有效，尤其是在选择强度较低的困难情况下。在放宽关于选择强度如何在不同位点变化的假设且不会像其他一些方法那样出现较高假阳性结果率的情况下，实现了检测能力的提升。我们还表明，即使在一些先前方法的结果可能产生误导的情况下，SLR方法也表现良好。
