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This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: jimmunol.0901537v1 183/7/4560    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Yuan, S. Articles by Xu, A. PubMed PubMed Citation Articles by Yuan, S. Articles by Xu, A.

Genomic and Functional Uniqueness of the TNF Receptor-Associated Factor Gene Family in Amphioxus, the Basal Chordate¹

State Key Laboratory of Biocontrol, National Engineering Research Center of South China Sea Marine Biotechnology, Department of Biochemistry, College of Life Sciences, Sun Yat-sen (Zhongshan) University, Guangzhou, People’s Republic of China

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-B activation mediated by human TRAF2 and 6. Amphioxus TRAF4 presented two unique functions: activation of the NF-B pathway and involvement in somite formation. Although amphioxus TRAF6 was conserved in activating NF-B 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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by Project 2007CB815800 of the National Basic Research Program (973), Projects 2006AA09Z433 and 2008AA092603 of the State High-Tech Development Project (863), Project 2007DFA30840 of International S&T Cooperation Program from the Ministry of Science and Technology of China, a key project (0107) from the Ministry of Education, a key project of Commission of Science and Technology of Guangdong Province and Guangzhou City, a project of Sun Yet-sen University Science Foundation, and the First Degree Supporting Project 20080440119 of China Postdoctoral Science Foundation.

² Address correspondence and reprint requests to Dr. Anlong Xu, Department of Biochemistry, College of Life Sciences, Sun Yat-Sen (Zhongshan) University, 135 XinGangXi Road, 510275, Guangzhou, People’s Republic of China. E-mail address: lssxal{at}mail.sysu.edu.cn

³ Abbreviations used in this paper: TRAF, TNF-associated factor; Amphi, refers to all amphioxus species; Bbt, Branchiostoma belcheri tsingtauense; Bf, Branchiostoma floridae; BC, bacterially challenged; ORF, open reading frame; TIR, Toll/IL-1R resistance domain; TRIF, Toll/IL-1R resistance domain containing adaptor-inducing IFN-β; UC, unchallenged.

⁴ The online version of this article contains supplemental material.