编者（熊荣川）按：正选择检测是指通过检测编码基因序列变化（或进化）中的非同义突变和同义突变的差异来量化进化压力对遗传变异的贡献；可用于推断基因的功能性或者功能位点，是一种常用的基因分析及筛选手段，下面是一段文摘，对如何进行有效的正选择检验进行了较为详细的阐述，具有较高的参考价值。

 Positiveselection was tested using the REL(HyPhy) [18] and CODEML (PAML) [19] methodsand these analyses revealed that codons exhibiting high dN/dS ratios, andtherefore likely to have been subjected to positive selection, were enriched inthe N-terminal cytoplasmic and TM domains in primate tetherins (Fig. 7).Tetherin evolution in primates was also evaluated under several standard modelsof sequence evolution as implemented in the CODEML program. These comprisethree nested pairs of models (M0 and M3; M1a and M2a; M7 and M8) in which thesecond model of each pair is derived from the first by allowing sites to evolveunder positive selection. Nested models were compared using the likelihoodratio test, and in each case allowing individual sites to evolve under positiveselection (M3, M2a, M8) gave a significantly better fit to the primate sequencedata than the corresponding model without positive selection (M0, M1a and M7,respectively) (Table 1). The M3, M2a and M8 models identified a largelyoverlapping set of sites in the tetherin coding sequence with dN/dS.1,consistent with an evolutionary history characterized by frequent episodes ofpositive selection. Notably, some codons that exhibited a high probability ofhaving evolved under positive selection coincided with residues that determinedthe effectiveness of Vpu antagonism (Fig. 7). However, there were numerousadditional codons, particularly in the tetherin cytoplasmic domain, that alsoexhibited high dN/dS ratios, suggesting that antagonists other than Vpu havealso imposed selective pressure on primate tetherin sequences.

参考文献

McNatt, M. W., T.Zang, T. Hatziioannou, M. Bartlett, I. B. Fofana, W. E. Johnson, S. J. Neil andP. D. Bieniasz (2009). Species-specific activity of HIV-1 Vpu and positiveselection of tetherin transmembrane domain variants. PLoS pathogens 5(2): e1000300.