ZFIN ID: ZDB-PUB-200307-19
The evolution of zebrafish RAG2 protein is required for adapting to the elevated body temperature of the higher endothermic vertebrates
Sun, A., Xu, K., Liu, H., Li, H., Shi, Y., Zhu, X., Liang, T., Li, X., Cao, X., Ji, Y., Jiang, T., Xu, C., Liu, X.
Date: 2020
Source: Scientific Reports   10: 4126 (Journal)
Registered Authors: Li, Xinyue
Keywords: none
MeSH Terms:
  • Animals
  • Body Temperature
  • Cell Line
  • Cell Proliferation/genetics
  • Cell Proliferation/physiology
  • DNA-Binding Proteins/genetics
  • DNA-Binding Proteins/metabolism*
  • Evolution, Molecular
  • Female
  • HEK293 Cells
  • Humans
  • Immunoblotting
  • Male
  • Mice
  • Mice, Inbred C57BL
  • NIH 3T3 Cells
  • Protein Stability
  • Real-Time Polymerase Chain Reaction
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed: 32139788 Full text @ Sci. Rep.
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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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