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首页> 美国卫生研究院文献>PLoS Clinical Trials >Variation in the Analysis of Positively Selected Sites Using Nonsynonymous/Synonymous Rate Ratios: An Example Using Influenza Virus
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Variation in the Analysis of Positively Selected Sites Using Nonsynonymous/Synonymous Rate Ratios: An Example Using Influenza Virus

机译：使用非同义词/同义词比率对阳性选择位点进行分析时的变异：使用流感病毒的示例

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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.
机译：显示非同义/同义比率（ω）> 1的基因中的位点经常被确定为正选择。为了检验这种分析的性能，从这项研究的七个重叠序列数据集中确定了H3N2亚型人流感病毒的HA1基因中ω比> 1的位点。我们的结果表明，即使它们以相似的簇为目标，ω比> 1的位点在数据集之间也存在显着差异，这表明该分析在鉴定阳性选择位点时可能灵敏度低或特异性低。从至少一个数据集计算得出的显示ω> 1的大多数（43/45）位点涉及B细胞表位，其覆盖蛋白质中不到一半的位点，这表明该分析可能灵敏度较低，而比低特异性。进一步发现，通过包含更多序列或覆盖更长的时间间隔无法提高分析灵敏度。以前，有些报道还可能使用ω比在病毒基因的阳性选择中仅识别出一部分位点。该分析的敏感性较低，可能是因为该基因在正选择下的某些位点在功能约束下也同时处于负（纯化）选择下，因此它们的ω比可能<1。从理论上讲，两个相反选择力作用下的位点同时仅支持某些非同义的变化，例如那些改变基因的抗原性并维持基因功能的基因。这项研究还表明，有时我们可以通过整合从多个数据集估计的阳性选择位点，使用ω比来确定阳性选择下的更多位点。

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