2. Academic Validation
  3. 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

  • Sci Rep. 2020 Mar 5;10(1):4126. doi: 10.1038/s41598-020-61019-w.
Ao Sun  # 1,  Ke Xu  # 1,  Haifeng Liu 1,  Hua Li 1,  Yaohuang Shi 1 2,  Xiaoyan Zhu 1,  Tao Liang 1,  Xinyue Li 1,  Xianxia Cao 1 2,  Yanhong Ji 3,  Taijiao Jiang 4,  Chenqi Xu 1,  Xiaolong Liu 5 6
Affiliations

Affiliations

  • 1 State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, China.
  • 2 School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China.
  • 3 Department of Pathogenic Biology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Centre, Xi'an, Shaanxi, 710061, China.
  • 4 Center of System Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100005, China.
  • 5 State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, China. liux@sibcb.ac.cn.
  • 6 School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China. liux@sibcb.ac.cn.
  • # Contributed equally.
PMID: 32139788 DOI: 10.1038/s41598-020-61019-w
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 Rag2KI/KI mice, which zRAG2 was substituted for mRAG2, was also severely impaired. Unexpectedly, Rag2KI/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.

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