Discovery of an Active RAG Transposon Illuminates the Origins of V(D)J Recombination. 2016

Shengfeng Huang, and Xin Tao, and Shaochun Yuan, and Yuhang Zhang, and Peiyi Li, and Helen A Beilinson, and Ya Zhang, and Wenjuan Yu, and Pierre Pontarotti, and Hector Escriva, and Yann Le Petillon, and Xiaolong Liu, and Shangwu Chen, and David G Schatz, and Anlong Xu
State Key Laboratory of Biocontrol, Guangdong Key Laboratory of Pharmaceutical Functional Genes, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, People's Republic of China.

Co-option of RAG1 and RAG2 for antigen receptor gene assembly by V(D)J recombination was a crucial event in the evolution of jawed vertebrate adaptive immunity. RAG1/2 are proposed to have arisen from a transposable element, but definitive evidence for this is lacking. Here, we report the discovery of ProtoRAG, a DNA transposon family from lancelets, the most basal extant chordates. A typical ProtoRAG is flanked by 5-bp target site duplications and a pair of terminal inverted repeats (TIRs) resembling V(D)J recombination signal sequences. Between the TIRs reside tail-to-tail-oriented, intron-containing RAG1-like and RAG2-like genes. We demonstrate that ProtoRAG was recently active in the lancelet germline and that the lancelet RAG1/2-like proteins can mediate TIR-dependent transposon excision, host DNA recombination, transposition, and low-efficiency TIR rejoining using reaction mechanisms similar to those used by vertebrate RAGs. We propose that ProtoRAG represents a molecular "living fossil" of the long-sought RAG transposon.

UI MeSH Term Description Entries
D004251 DNA Transposable Elements Discrete segments of DNA which can excise and reintegrate to another site in the genome. Most are inactive, i.e., have not been found to exist outside the integrated state. DNA transposable elements include bacterial IS (insertion sequence) elements, Tn elements, the maize controlling elements Ac and Ds, Drosophila P, gypsy, and pogo elements, the human Tigger elements and the Tc and mariner elements which are found throughout the animal kingdom. DNA Insertion Elements,DNA Transposons,IS Elements,Insertion Sequence Elements,Tn Elements,Transposable Elements,Elements, Insertion Sequence,Sequence Elements, Insertion,DNA Insertion Element,DNA Transposable Element,DNA Transposon,Element, DNA Insertion,Element, DNA Transposable,Element, IS,Element, Insertion Sequence,Element, Tn,Element, Transposable,Elements, DNA Insertion,Elements, DNA Transposable,Elements, IS,Elements, Tn,Elements, Transposable,IS Element,Insertion Element, DNA,Insertion Elements, DNA,Insertion Sequence Element,Sequence Element, Insertion,Tn Element,Transposable Element,Transposable Element, DNA,Transposable Elements, DNA,Transposon, DNA,Transposons, DNA
D004268 DNA-Binding Proteins Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases. DNA Helix Destabilizing Proteins,DNA-Binding Protein,Single-Stranded DNA Binding Proteins,DNA Binding Protein,DNA Single-Stranded Binding Protein,SS DNA BP,Single-Stranded DNA-Binding Protein,Binding Protein, DNA,DNA Binding Proteins,DNA Single Stranded Binding Protein,DNA-Binding Protein, Single-Stranded,Protein, DNA-Binding,Single Stranded DNA Binding Protein,Single Stranded DNA Binding Proteins
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D060152 V(D)J Recombination The process by which the V (variable), D (diversity), and J (joining) segments of IMMUNOGLOBULIN GENES or T-CELL RECEPTOR GENES are assembled during the development of LYMPHOID CELLS using NONHOMOLOGOUS DNA END-JOINING. VDJ Recombination,Recombination, VDJ,Recombinations, VDJ,VDJ Recombinations
D018398 Homeodomain Proteins Proteins encoded by homeobox genes (GENES, HOMEOBOX) that exhibit structural similarity to certain prokaryotic and eukaryotic DNA-binding proteins. Homeodomain proteins are involved in the control of gene expression during morphogenesis and development (GENE EXPRESSION REGULATION, DEVELOPMENTAL). Homeo Domain Protein,Homeobox Protein,Homeobox Proteins,Homeodomain Protein,Homeoprotein,Homeoproteins,Homeotic Protein,Homeo Domain Proteins,Homeotic Proteins,Domain Protein, Homeo,Protein, Homeo Domain,Protein, Homeobox,Protein, Homeodomain,Protein, Homeotic,Proteins, Homeo Domain,Proteins, Homeobox,Proteins, Homeodomain,Proteins, Homeotic
D019143 Evolution, Molecular The process of cumulative change at the level of DNA; RNA; and PROTEINS, over successive generations. Molecular Evolution,Genetic Evolution,Evolution, Genetic
D020079 Terminal Repeat Sequences Nucleotide sequences repeated on both the 5' and 3' ends of a sequence under consideration. For example, the hallmarks of a transposon are that it is flanked by inverted repeats on each end and the inverted repeats are flanked by direct repeats. The Delta element of Ty retrotransposons and LTRs (long terminal repeats) are examples of this concept. Delta Elements,Flanking Repeat Sequences,Inverted Terminal Repeat,Long Terminal Repeat,R Repetitive Sequence,Terminal Repeat,Delta Element,Element, Delta,Elements, Delta,Flanking Repeat Sequence,Long Terminal Repeats,R Repetitive Sequences,Repeat Sequence, Flanking,Repeat Sequence, Terminal,Repeat Sequences, Flanking,Repeat Sequences, Terminal,Repeat, Long Terminal,Repeat, Terminal,Repeats, Long Terminal,Repeats, Terminal,Repetitive Sequence, R,Repetitive Sequences, R,Sequence, Flanking Repeat,Sequence, R Repetitive,Sequence, Terminal Repeat,Sequences, Flanking Repeat,Sequences, R Repetitive,Sequences, Terminal Repeat,Terminal Repeat Sequence,Terminal Repeat, Long,Terminal Repeats,Terminal Repeats, Long
D064175 Lancelets Small fish-like marine creatures often used in phylogenetic comparative studies of CHORDATES. Amphioxi,Amphioxus,Amphioxus lanceolatus,Branchiostoma,Branchiostoma belcheri,Branchiostoma floridae,Branchiostoma japonicum,Branchiostoma lanceolatum,Branchiostoma nigeriense,Florida Lancelet,Mediterranean Amphioxus,Amphioxus, Mediterranean,Branchiostoma belcherus,Branchiostoma japonicums,Branchiostoma lanceolatums,Branchiostoma nigerienses,Branchiostomas,Florida Lancelets,Lancelet,Lancelet, Florida,Lancelets, Florida,belcheri, Branchiostoma,japonicum, Branchiostoma,lanceolatums, Branchiostoma,nigerienses, Branchiostoma

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