PUBLICATION
The evolution of zebrafish RAG2 protein is required for adapting to the elevated body temperature of the higher endothermic vertebrates
- Authors
- 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.
- ID
- ZDB-PUB-200307-19
- Date
- 2020
- Source
- Scientific Reports 10: 4126 (Journal)
- Registered Authors
- Li, Xinyue
- Keywords
- none
- MeSH Terms
-
- HEK293 Cells
- Animals
- Body Temperature
- Protein Stability
- Male
- Cell Proliferation/genetics
- Cell Proliferation/physiology
- Female
- Evolution, Molecular
- Cell Line
- Mice
- DNA-Binding Proteins/genetics
- DNA-Binding Proteins/metabolism*
- Humans
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- NIH 3T3 Cells
- Mice, Inbred C57BL
- Real-Time Polymerase Chain Reaction
- Zebrafish
- Immunoblotting
- PubMed
- 32139788 Full text @ Sci. Rep.
Citation
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. (2020) The evolution of zebrafish RAG2 protein is required for adapting to the elevated body temperature of the higher endothermic vertebrates. Scientific Reports. 10:4126.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping