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Updated: Oct 16, 2025
12:02
Molecular Evolution of the Tre Recombinase
Published on: May 29, 2008
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Structural insights into the evolution of the RAG recombinase
Chang Liu1, Yuhang Zhang2, Catherine C Liu3
1Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA.
Nature Reviews. Immunology
|October 22, 2021
Summary
The evolution of adaptive immunity in jawed vertebrates involved the domestication of a transposable element into the RAG recombinase. This process yielded a highly regulated enzyme essential for V(D)J recombination and immune system development.
Area of Science:
- Immunology
- Molecular Biology
- Evolutionary Biology
Background:
- Adaptive immunity in jawed vertebrates depends on V(D)J recombination, mediated by the RAG1-RAG2 recombinase.
- Evidence suggests RAG and V(D)J recombination originated from a RAG-like (RAGL) transposable element via transposon molecular domestication.
Purpose of the Study:
- To review recent advances in understanding the functional and structural evolution of RAG recombinase.
- To trace the evolutionary adaptations from RAGL enzymes to the RAG recombinase.
Main Methods:
- Comparative genome analyses.
- Structural biology.
- Biochemical studies.
Main Results:
- RAG evolution involved transitions in DNA binding, protein-DNA complex dynamics, and amino acid sequences.
- A modular design and regulatory mechanisms suppressed transposition, enabling RAG survival.
- Structural insights reveal adaptations for regulated cleavage activity.
Conclusions:
- RAG evolution from RAGL elements showcases molecular domestication in vertebrate immunity.
- Understanding these evolutionary changes provides insights into immune system development and genome stability.
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