Genomic and Functional Uniqueness of the TNF Receptor-Associated Factor Gene Family in Amphioxus, the Basal Chordate1
Genomic and Functional Uniqueness of the TNF Receptor-Associated Factor Gene Family in Amphioxus, the Basal Chordate1
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DOI：
10.4049/jimmunol.0901537
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发表时间：
2009-10
期刊：
影响因子：
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通讯作者：
Shaochun Yuan;Tong Liu;Shengfeng Huang;Tao Wu;Ling Huang;Huiling Liu;Xin Tao;Manyi Yang;Kui Wu;Yanhong Yu;Meiling Dong;A. Xu
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文献类型：
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作者：
Shaochun Yuan;Tong Liu;Shengfeng Huang;Tao Wu;Ling Huang;Huiling Liu;Xin Tao;Manyi Yang;Kui Wu;Yanhong Yu;Meiling Dong;A. Xu
肿瘤坏死因子相关因子(TRAF)家族，先天免疫信号的关键适配组，在文昌鱼中增加到24个，文昌鱼是脊索动物中最古老的谱系。为了解决这些扩展分子如何进化以适应不断变化的TRAF介导的信号通路，我们在这里对四个不同的文昌鱼TRAF组进行了基因组和功能比较。我们发现，文昌鱼TRAF1/2和TRAF3谱系的扩展是由谱系特异性的复制和重排引起的，而TRAF4和TRAF6保持了相对稳定的基因组和蛋白质结构。文昌鱼TRAF1/2和TRAF3分子在微生物感染后表现出不同的表达模式，其中一些分子可以减弱人TRAF2和TRAF6介导的NF-κB的激活。文昌鱼TRAF4具有两个独特的功能：激活NF-κB途径和参与体节形成。虽然文昌鱼TRAF6在激活NF-κB途径进行抗菌防御方面是保守的，但其机制与在人类中观察到的机制不同。综上所述，我们的发现揭示了TRAF家族在这个基础脊索中进化的独特性，并表明TRAF家族的基因组复制和功能差异对于目前人类TRAF介导的信号通路的形式是重要的。
The TNF-associated factor (TRAF) family, the crucial adaptor group in innate immune signaling, increased to 24 in amphioxus, the oldest lineage of the Chordata. To address how these expanded molecules evolved to adapt to the changing TRAF mediated signaling pathways, here we conducted genomic and functional comparisons of four distinct amphioxus TRAF groups with their human counterparts. We showed that lineage-specific duplication and rearrangement were responsible for the expansion of amphioxus TRAF1/2 and 3 lineages, whereas TRAF4 and 6 maintained a relatively stable genome and protein structure. Amphioxus TRAF1/2 and 3 molecules displayed various expression patterns in response to microbial infection, and some of them can attenuate the NF-κB activation mediated by human TRAF2 and 6. Amphioxus TRAF4 presented two unique functions: activation of the NF-κB pathway and involvement in somite formation. Although amphioxus TRAF6 was conserved in activating NF-κB pathway for antibacterial defense, the mechanism was not the same as that observed in humans. In summary, our findings reveal the evolutionary uniqueness of the TRAF family in this basal chordate, and suggest that genomic duplication and functional divergence of the TRAF family are important for the current form of the TRAF-mediated signaling pathways in humans.