The evolution of zebrafish RAG2 protein is required for adapting to the elevated body temperature of the higher endothermic vertebrates

作者：Ao Sun, Ke Xu, Haifeng Liu, Hua Li, Yaohuang Shi, Xiaoyan Zhu, Liang Tao, Xinyue Li, Xianxia Cao, Yanhong Ji, Taijiao Jiang, Chenqi Xu, Xiaolong Liu · 发表于：Scientific Reports · 年份：2020 · DOI：10.1038/s41598-020-61019-w · 被引用次数：2 · 研究领域：Immune Cell Function and Interaction、Zebrafish Biomedical Research Applications、Adipose Tissue and Metabolism

Abstract 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 of Rag2 KI/KI mice, which zRAG2 was substituted for mRAG2, was also severely impaired. Unexpectedly, Rag2 KI/KI mice 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.