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RAG1 core and V(D)J recombination signal sequences were derived from Transib transposons.

Kapitonov VV, Jurka J - PLoS Biol. (2005)

Bottom Line: Yet no transposase sequence similar to RAG1 or RAG2 has been found.Our results provide the first direct evidence linking RAG1 and RSSs to a specific superfamily of DNA transposons and indicate that the V(D)J machinery evolved from transposons.We also suggest that the RAG2 protein was not encoded by ancient Transib transposons but emerged in jawed vertebrates as a counterpart of RAG1 necessary for the V(D)J recombination reaction.

View Article: PubMed Central - PubMed

Affiliation: Genetic Information Research Institute, Mountain View, California, USA. vladimir@girinst.org

ABSTRACT
The V(D)J recombination reaction in jawed vertebrates is catalyzed by the RAG1 and RAG2 proteins, which are believed to have emerged approximately 500 million years ago from transposon-encoded proteins. Yet no transposase sequence similar to RAG1 or RAG2 has been found. Here we show that the approximately 600-amino acid "core" region of RAG1 required for its catalytic activity is significantly similar to the transposase encoded by DNA transposons that belong to the Transib superfamily. This superfamily was discovered recently based on computational analysis of the fruit fly and African malaria mosquito genomes. Transib transposons also are present in the genomes of sea urchin, yellow fever mosquito, silkworm, dog hookworm, hydra, and soybean rust. We demonstrate that recombination signal sequences (RSSs) were derived from terminal inverted repeats of an ancient Transib transposon. Furthermore, the critical DDE catalytic triad of RAG1 is shared with the Transib transposase as part of conserved motifs. We also studied several divergent proteins encoded by the sea urchin and lancelet genomes that are 25%-30% identical to the RAG1 N-terminal domain and the RAG1 core. Our results provide the first direct evidence linking RAG1 and RSSs to a specific superfamily of DNA transposons and indicate that the V(D)J machinery evolved from transposons. We propose that only the RAG1 core was derived from the Transib transposase, whereas the N-terminal domain was assembled from separate proteins of unknown function that may still be active in sea urchin, lancelet, hydra, and starlet sea anemone. We also suggest that the RAG2 protein was not encoded by ancient Transib transposons but emerged in jawed vertebrates as a counterpart of RAG1 necessary for the V(D)J recombination reaction.

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Schematic Structure of the Sea Urchin RAG1-Like SequencesContig accession numbers are shown in the left column. Inverted complement contigs are marked by “c” followed by the contig number. In each contig, RAG1-like proteins (white rectangle) are schematically aligned with the human RAG1 core (top rectangle). Nucleotide positions of the RAG1-like sequences are shown beneath the white rectangles. Three pairs of recently duplicated sequences (nucleotide identity is higher than 95%) are underlined by red, green, and black lines, respectively. Transposable and repetitive elements detected in the flanking regions are marked by painted rectangles. Names of these elements are shown above the rectangles. Asterisks denote stop codons in the corresponding RAG1-like sequences. BLASTP E-values characterizing similarities between the sea urchin and RAG1 proteins are shown above the white rectangles. Multiple alignment of these protein sequences is reported in Figure S5.
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pbio-0030181-g005: Schematic Structure of the Sea Urchin RAG1-Like SequencesContig accession numbers are shown in the left column. Inverted complement contigs are marked by “c” followed by the contig number. In each contig, RAG1-like proteins (white rectangle) are schematically aligned with the human RAG1 core (top rectangle). Nucleotide positions of the RAG1-like sequences are shown beneath the white rectangles. Three pairs of recently duplicated sequences (nucleotide identity is higher than 95%) are underlined by red, green, and black lines, respectively. Transposable and repetitive elements detected in the flanking regions are marked by painted rectangles. Names of these elements are shown above the rectangles. Asterisks denote stop codons in the corresponding RAG1-like sequences. BLASTP E-values characterizing similarities between the sea urchin and RAG1 proteins are shown above the white rectangles. Multiple alignment of these protein sequences is reported in Figure S5.

Mentions: Using RAG1 proteins as query sequences in a WU BLAST search against sea urchin contigs sequenced at Baylor College (see Materials and Methods), we identified eight proteins approximately 30% identical to portions of the RAG1 core and approximately 50% identical to each other (see Figures 2, 5, and S5). Only one protein is present in two copies, which are 94% identical to each other at the DNA level (contigs 81987 and 6797). Both copies appear to be encoded by pseudogenes damaged by a stop codon at the same position of each protein. Interestingly, the 6,690-bp contig 6797 harbours two additional defective pseudogenes coding for different RAG1 core–like proteins (Figure 5). We also identified a 597-aa protein sequence encoded by a single open reading frame (contig 29068, positions 1157–2944), which is 28% identical to nearly the entire RAG1 core (positions 461–1002 in the human RAG1, Figure S5). Extensive analysis of the flanks failed to show any hallmarks of putative transposons that might be associated with this RAG1-like protein, and we did not find any evidence indicating that other RAG1 core–like proteins are encoded by transposable elements (Figure 5).


RAG1 core and V(D)J recombination signal sequences were derived from Transib transposons.

Kapitonov VV, Jurka J - PLoS Biol. (2005)

Schematic Structure of the Sea Urchin RAG1-Like SequencesContig accession numbers are shown in the left column. Inverted complement contigs are marked by “c” followed by the contig number. In each contig, RAG1-like proteins (white rectangle) are schematically aligned with the human RAG1 core (top rectangle). Nucleotide positions of the RAG1-like sequences are shown beneath the white rectangles. Three pairs of recently duplicated sequences (nucleotide identity is higher than 95%) are underlined by red, green, and black lines, respectively. Transposable and repetitive elements detected in the flanking regions are marked by painted rectangles. Names of these elements are shown above the rectangles. Asterisks denote stop codons in the corresponding RAG1-like sequences. BLASTP E-values characterizing similarities between the sea urchin and RAG1 proteins are shown above the white rectangles. Multiple alignment of these protein sequences is reported in Figure S5.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1131882&req=5

pbio-0030181-g005: Schematic Structure of the Sea Urchin RAG1-Like SequencesContig accession numbers are shown in the left column. Inverted complement contigs are marked by “c” followed by the contig number. In each contig, RAG1-like proteins (white rectangle) are schematically aligned with the human RAG1 core (top rectangle). Nucleotide positions of the RAG1-like sequences are shown beneath the white rectangles. Three pairs of recently duplicated sequences (nucleotide identity is higher than 95%) are underlined by red, green, and black lines, respectively. Transposable and repetitive elements detected in the flanking regions are marked by painted rectangles. Names of these elements are shown above the rectangles. Asterisks denote stop codons in the corresponding RAG1-like sequences. BLASTP E-values characterizing similarities between the sea urchin and RAG1 proteins are shown above the white rectangles. Multiple alignment of these protein sequences is reported in Figure S5.
Mentions: Using RAG1 proteins as query sequences in a WU BLAST search against sea urchin contigs sequenced at Baylor College (see Materials and Methods), we identified eight proteins approximately 30% identical to portions of the RAG1 core and approximately 50% identical to each other (see Figures 2, 5, and S5). Only one protein is present in two copies, which are 94% identical to each other at the DNA level (contigs 81987 and 6797). Both copies appear to be encoded by pseudogenes damaged by a stop codon at the same position of each protein. Interestingly, the 6,690-bp contig 6797 harbours two additional defective pseudogenes coding for different RAG1 core–like proteins (Figure 5). We also identified a 597-aa protein sequence encoded by a single open reading frame (contig 29068, positions 1157–2944), which is 28% identical to nearly the entire RAG1 core (positions 461–1002 in the human RAG1, Figure S5). Extensive analysis of the flanks failed to show any hallmarks of putative transposons that might be associated with this RAG1-like protein, and we did not find any evidence indicating that other RAG1 core–like proteins are encoded by transposable elements (Figure 5).

Bottom Line: Yet no transposase sequence similar to RAG1 or RAG2 has been found.Our results provide the first direct evidence linking RAG1 and RSSs to a specific superfamily of DNA transposons and indicate that the V(D)J machinery evolved from transposons.We also suggest that the RAG2 protein was not encoded by ancient Transib transposons but emerged in jawed vertebrates as a counterpart of RAG1 necessary for the V(D)J recombination reaction.

View Article: PubMed Central - PubMed

Affiliation: Genetic Information Research Institute, Mountain View, California, USA. vladimir@girinst.org

ABSTRACT
The V(D)J recombination reaction in jawed vertebrates is catalyzed by the RAG1 and RAG2 proteins, which are believed to have emerged approximately 500 million years ago from transposon-encoded proteins. Yet no transposase sequence similar to RAG1 or RAG2 has been found. Here we show that the approximately 600-amino acid "core" region of RAG1 required for its catalytic activity is significantly similar to the transposase encoded by DNA transposons that belong to the Transib superfamily. This superfamily was discovered recently based on computational analysis of the fruit fly and African malaria mosquito genomes. Transib transposons also are present in the genomes of sea urchin, yellow fever mosquito, silkworm, dog hookworm, hydra, and soybean rust. We demonstrate that recombination signal sequences (RSSs) were derived from terminal inverted repeats of an ancient Transib transposon. Furthermore, the critical DDE catalytic triad of RAG1 is shared with the Transib transposase as part of conserved motifs. We also studied several divergent proteins encoded by the sea urchin and lancelet genomes that are 25%-30% identical to the RAG1 N-terminal domain and the RAG1 core. Our results provide the first direct evidence linking RAG1 and RSSs to a specific superfamily of DNA transposons and indicate that the V(D)J machinery evolved from transposons. We propose that only the RAG1 core was derived from the Transib transposase, whereas the N-terminal domain was assembled from separate proteins of unknown function that may still be active in sea urchin, lancelet, hydra, and starlet sea anemone. We also suggest that the RAG2 protein was not encoded by ancient Transib transposons but emerged in jawed vertebrates as a counterpart of RAG1 necessary for the V(D)J recombination reaction.

Show MeSH
Related in: MedlinePlus