molecular evolution of the primate antiviral restriction factor tetherin分子进化的灵长类动物抗病毒tetherin限制因素.pdfVIP

Molecular Evolution of the Primate Antiviral Restriction Factor Tetherin 1 1 2 1 Jun Liu , Keping Chen , Jian-Hua Wang , Chiyu Zhang * 1 Institute of Life Sciences, Jiangsu University, Zhenjiang, Jiangsu, China, 2 Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China Abstract Background: Tetherin is a recently identified antiviral restriction factor that restricts HIV-1 particle release in the absence of the HIV-1 viral protein U (Vpu). It is reminiscent of APOBEC3G and TRIM5a that also antagonize HIV. APOBEC3G and TRIM5a have been demonstrated to evolve under pervasive positive selection throughout primate evolution, supporting the red- queen hypothesis. Therefore, one naturally presumes that Tetherin also evolves under pervasive positive selection throughout primate evolution and supports the red-queen hypothesis. Here, we performed a detailed evolutionary analysis to address this presumption. Methodology/Principal Findings: Results of non-synonymous and synonymous substitution rates reveal that Tetherin as a whole experiences neutral evolution rather than pervasive positive selection throughout primate evolution, as well as in non-primate mammal evolution. Sliding-window analyses show that the regions of the primate Tetherin that interact with viral proteins are under positive selection or relaxed purifying selection. In particular, the sites identified under positive selection generally focus on these regions, indicating that the main selective pressure acting on the primate Tetherin comes from virus infection. The branch-site model detected positive selection acting on the ancestral branch of the New World Monkey lineage, suggesting an episodic adaptive evolution. The positive selection was also found in duplicated