China Animal Health and Epidemiology Center, Qingdao, China.
PLoS One. 2011;6(5):e19996. doi: 10.1371/journal.pone.0019996. Epub 2011 May 24.
Sites in a gene showing the nonsynonymous/synonymous rate ratio (ω) >1 have been frequently identified to be under positive selection. To examine the performance of such analysis, sites of the ω ratio >1 in the HA1 gene of H3N2 subtype human influenza viruses were identified from seven overlapping sequence data sets in this study. Our results showed that the sites of the ω ratio >1 were of significant variation among the data sets even though they targeted similar clusters, indicating that the analysis is likely to be either of low sensitivity or of low specificity in identifying sites under positive selection. Most (43/45) of the sites showing ω >1 calculated from at least one data set are involved in B-cell epitopes which cover less than a half sites in the protein, suggesting that the analysis is likely to be of low sensitivity rather than of low specificity. It was further found that the analysis sensitivity could not be enhanced by including more sequences or covering longer time intervals. Previously some reports also likely identified only a portion of the sites under positive selection in the viral gene using the ω ratio. Low sensitivity of the analysis may result from that some sites under positive selection in the gene are also under negative (purifying) selection simultaneously for functional constrains, and so their ω ratios could be <1. Theoretically, the sites under the two opposite selection forces at the same time favor only certain nonsynonymous changes, e.g. those changing the antigenicity of the gene and maintaining the gene function. This study also suggested that sometimes we can identify more sites under positive selection using the ω ratio by integrating the positively selected sites estimated from multiple data sets.
在基因中，显示非同义/同义比率（ω）> 1 的位点经常被鉴定为受到正选择的影响。为了检验这种分析的性能，本研究从七个重叠的序列数据集鉴定了 H3N2 亚型人流感病毒 HA1 基因中ω比值> 1 的位点。我们的结果表明，即使这些数据集中针对相似的聚类，ω比值> 1 的位点在数据集中存在显著的变异，这表明该分析在识别正选择下的位点时可能要么敏感性低，要么特异性低。从至少一个数据集计算出的ω> 1 的 45 个位点中的大多数（43/45）都涉及 B 细胞表位，这些表位覆盖不到蛋白质中一半的位点，这表明该分析可能是敏感性低而不是特异性低。进一步发现，通过增加更多的序列或覆盖更长的时间间隔，分析的敏感性不能得到提高。以前的一些报告也可能使用ω比值仅鉴定了病毒基因中部分受到正选择的位点。分析敏感性低可能是由于基因中某些受到正选择的位点同时受到功能约束的负选择（净化选择），因此它们的ω比值可能<1。从理论上讲，同时受到两种相反选择力影响的位点只有利于某些非同义变化，例如那些改变基因抗原性并保持基因功能的变化。本研究还表明，通过整合从多个数据集估计的正选择位点，有时我们可以使用ω比值识别更多的正选择位点。
