The evolution of zebrafish RAG2 protein is required for adapting to the elevated body temperature of the higher endothermic vertebrates
The evolution of zebrafish RAG2 protein is required for adapting to the elevated body temperature of the higher endothermic vertebrates
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斑马鱼 RAG2 蛋白的进化是适应高等吸热脊椎动物升高的体温所必需的
DOI：
10.1038/s41598-020-61019-w
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发表时间：
2020-03
影响因子：
4.6
通讯作者：
Liu Xiaolong
中科院分区：
文献类型：
--
作者：
Sun Ao;Xu Ke;Liu Haifeng;Li Hua;Shi Yaohuang;Zhu Xiaoyan;Liang Tao;Li Xinyue;Cao Xianxia;Ji Yanhong;Jiang Taijiao;Xu Chenqi;Liu Xiaolong
重组激活基因（RAG或RAG 1/RAG 2复合物）介导的适应性免疫系统是有颌脊椎动物的标志。据报道，RAG起源于无脊椎动物。然而，RAG是否进一步进化，一旦它出现在有颌脊椎动物仍然在很大程度上未知。在这里，我们发现斑马鱼RAG（zRAG）的活性低于小鼠RAG（mRAG）。有趣的是，与mRAG相比，斑马鱼RAG 2（zRAG 2）而不是斑马鱼RAG 1的减弱的稳定性在37 °C下导致降低的V（D）J重组效率，37 °C是除鸟类之外的大多数恒温动物的体温。重要的是，较低的温度28 °C，这是斑马鱼生长的最佳温度，通过提高zRAG 2的稳定性，使zRAG的重组效率与mRAG相似。与前述观察一致，其中zRAG 2取代mRAG 2的Rag 2KI/KImice的V（D）J重组也严重受损。出乎意料的是，Rag 2KI/KImice出现恶病质综合征，并伴有过早死亡。综上所述，我们的研究结果表明，斑马鱼RAG 2蛋白的进化是适应较高吸热脊椎动物升高的体温所必需的。
The recombination activating gene (RAG or RAG1/RAG2 complex)-mediated adaptive immune system is a hallmark of jawed vertebrates. It has been reported that RAG originated in invertebrates. However, whether RAG further evolved once it arose in jawed vertebrates remains largely unknown. Here, we found that zebrafish RAG (zRAG) had a lower activity than mouse RAG (mRAG). Intriguingly, the attenuated stability of zebrafish RAG2 (zRAG2), but not zebrafish RAG1, caused the reduced V(D)J recombination efficiency compared to mRAG at 37 °C which are the body temperature of most endotherms except birds. Importantly, the lower temperature 28 °C, which is the best temperature for zebrafish growth, made the recombination efficiency of zRAG similar to that of mRAG by improving the stability of zRAG2. Consistent with the prementioned observation, the V(D)J recombination ofRag2KI/KImice, which zRAG2 was substituted for mRAG2, was also severely impaired. Unexpectedly,Rag2KI/KImice developed cachexia syndromes accompanied by premature death. Taken together, our findings illustrate that the evolution of zebrafish RAG2 protein is required for adapting to the elevated body temperature of the higher endothermic vertebrates.
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DOI：
10.1073/pnas.1318843111
发表时间：
2014-01-07
影响因子：
11.1
作者：
Zhang, Yanni;Xu, Ke;Liu, Xiaolong
通讯作者：
Liu, Xiaolong
影响因子：
5.3
作者：
P. Swanson;S. Desiderio
通讯作者：
P. Swanson;S. Desiderio
影响因子：
7.7
作者：
Parichy DM
通讯作者：
Parichy DM
影响因子：
3.4
作者：
Danijela Briggs;D. Arnott
通讯作者：
Danijela Briggs;D. Arnott
影响因子：
15.9
作者：
Couedel, Chrystelle;Roman, Christopher;Cortes, Patricia
通讯作者：
Cortes, Patricia