Impact of RAG Transposon Co-option on the Evolution of the Jawed Vertebrate Immune System
Abstract
This article aims to review the current knowledge in comparative immunology and present updated hypotheses regarding the evolution of the immune system. Our primary focus is the co-option of the RAG transposon and its role in the development of the V(D)J recombination system. We propose that this co-option occurred in two distinct steps. First, the RAG transposon, along with other eukaryote-specific transposon families such as HAT, co-opted endogenous genes in early eukaryotic ancestors, facilitating the development of a novel transposition mechanism. The second step involved the specific co-option of RAG and endogenous genes into the V(D)J recombination system, marking a significant evolutionary event in jawed vertebrates.
We will then explore the broader implications of this event, particularly how the emergence of the V(D)J recombination system influenced the evolution of the immune system in jawed vertebrates. First, we briefly present our previously published hypothesis suggesting that the establishment of this system played a pivotal role in driving MHC polymorphism. Second, building on the assertion that the core components of the immune system in jawed vertebrates-MHC, TCR (alpha beta, and gamma delta), and immunoglobulins-were present in their common ancestors, we propose, based on phylogenomic analyses, that these proteins evolved through gene duplication into multigene families with diverse functions. The proteins encoded by these duplicated genes interact with other molecules via ligandreceptor mechanisms or direct interactions, resulting in co-activation, co-inhibition, or co-regulation of immune responses. Some of these interacting proteins have retained their ancestral functions while being incorporated into the newly evolving immune system, while others acquired new roles through processes such as neofunctionalization and exon shuffling.These evolutionary changes reflect not only the increasing complexity of the adaptive immune system but also the emergence of novel innate immune mechanisms specific to jawed vertebrates .
Therefore, the co-option of the RAG transposon has had profound consequences on the evolution of the immune system in jawed vertebrates, driving innovations in both adaptive and innate immunity.
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BibTeX
@article{pontarotti2026impact,
title = {{Impact of RAG Transposon Co-option on the Evolution of the Jawed Vertebrate Immune System}},
author = {Pierre Pontarotti and Vivek Keshri},
journal = {Immunogenetics},
year = {2026},
month = oct,
doi = {10.1007/s00251-026-01414-1},
url = {https://hal.science/hal-04978008v2},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Impact of RAG Transposon Co-option on the Evolution of the Jawed Vertebrate Immune System
AU - Pierre Pontarotti
AU - Vivek Keshri
PY - 2026
DA - 2026/10/28
JO - Immunogenetics
DO - 10.1007/s00251-026-01414-1
UR - https://hal.science/hal-04978008v2
AB - This article aims to review the current knowledge in comparative immunology and present updated hypotheses regarding the evolution of the immune system. Our primary focus is the co-option of the RAG transposon and its role in the development of the V(D)J recombination system. We propose that this co-option occurred in two distinct steps. First, the RAG transposon, along with other eukaryote-specific transposon families such as HAT, co-opted endogenous genes in early eukaryotic ancestors, facilitating the development of a novel transposition mechanism. The second step involved the specific co-option of RAG and endogenous genes into the V(D)J recombination system, marking a significant evolutionary event in jawed vertebrates. We will then explore the broader implications of this event, particularly how the emergence of the V(D)J recombination system influenced the evolution of the immune system in jawed vertebrates. First, we briefly present our previously published hypothesis suggesting that the establishment of this system played a pivotal role in driving MHC polymorphism. Second, building on the assertion that the core components of the immune system in jawed vertebrates-MHC, TCR (alpha beta, and gamma delta), and immunoglobulins-were present in their common ancestors, we propose, based on phylogenomic analyses, that these proteins evolved through gene duplication into multigene families with diverse functions. The proteins encoded by these duplicated genes interact with other molecules via ligandreceptor mechanisms or direct interactions, resulting in co-activation, co-inhibition, or co-regulation of immune responses. Some of these interacting proteins have retained their ancestral functions while being incorporated into the newly evolving immune system, while others acquired new roles through processes such as neofunctionalization and exon shuffling.These evolutionary changes reflect not only the increasing complexity of the adaptive immune system but also the emergence of novel innate immune mechanisms specific to jawed vertebrates . Therefore, the co-option of the RAG transposon has had profound consequences on the evolution of the immune system in jawed vertebrates, driving innovations in both adaptive and innate immunity.
SN - 0093-7711
SN - 1432-1211
ER -