Variation in the analysis of positively selected sites using nonsynonymous/synonymous rate ratios: an example using influenza virus.
Variation in the analysis of positively selected sites using nonsynonymous/synonymous rate ratios: an example using influenza virus.
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使用非同义/同义率比率分析正选位点的变化：使用流感病毒的示例。
DOI：
10.1371/journal.pone.0019996
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Sun Y
中科院分区：
文献类型：
--
作者：
Chen J;Sun Y
基因中非同义/同义比率（ω）>1的位点经常被鉴定为正选择。为了检验这种分析的性能，本研究从7个重叠序列数据集中鉴定了H3 N2亚型人流感病毒HA 1基因中ω比率>1的位点。我们的结果表明，ω比>1的位点在数据集中具有显著差异，即使它们针对相似的簇，这表明在正选择下识别位点的分析可能是低灵敏度或低特异性的。从至少一个数据集计算的显示ω >1的大多数（43/45）位点涉及覆盖蛋白质中不到一半位点的B细胞表位，这表明分析可能是低灵敏度而不是低特异性。进一步发现，分析灵敏度不能通过包括更多序列或覆盖更长时间间隔来增强。以前的一些报道也可能只确定了一部分的网站在积极选择的病毒基因使用ω比。分析的低灵敏度可能是由于基因中正选择下的一些位点由于功能限制也同时处于负（纯化）选择下，因此它们的ω比可能<1。从理论上讲，同时处于两种相反选择力下的位点只有利于某些非同义的变化，例如改变基因抗原性和保持基因功能的变化。这项研究还表明，有时我们可以确定更多的网站下的积极选择使用ω比通过整合的积极选择网站估计从多个数据集。
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.
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影响因子：
10.7
作者：
Yang, ZH;Wong, WSW;Nielsen, R
通讯作者：
Nielsen, R
影响因子：
64.8
作者：
WILEY, DC;WILSON, IA;SKEHEL, JJ
通讯作者：
SKEHEL, JJ
DOI：
10.1098/rspb.2009.0328
发表时间：
2009-08-22
影响因子：
4.7
作者：
Van der Merwe, Marlien M.;Kinnear, Mark W.;Burdon, Jeremy J.
通讯作者：
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DOI：
10.1073/pnas.94.15.7712
发表时间：
1997-07-22
影响因子：
11.1
作者：
Fitch, WM;Bush, RM;Cox, NJ
通讯作者：
Cox, NJ
影响因子：
10.7
作者：
Suzuki, Yoshiyuki
通讯作者：
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