Limits...
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.

Show MeSH

Related in: MedlinePlus

Schematic Presentation of Transib transposons, RAG1, RAG2, and RAG1-Like Proteins in EukaryotesThe basic timescale of the evolutionary tree is based on published literature [49–51]. Red circles mark species in which Transib TPases were found. Gray squares indicate RAG2; orange and blue ellipses show the RAG1 core and RAG1 N-terminal domain, respectively. Overall taxonomy, including common and Latin names, is reported on the right side of the figure. A question mark at the lamprey lineage indicates insufficient sequence data. A lack of any labels means that the Transib TPase and RAG1/2 are not present in the sequenced portions of the corresponding genomes. Among branches lacking Transib TPases, only lamprey and crocodile genomes are not extensively sequenced to date. In sea anemone, the RAG1 core–like protein is capped by the ring finger motif, which also forms the C-terminus in the RAG1 N-terminal domain. In fungi, the Transib TPase was detected in soybean rust only.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC1131882&req=5

pbio-0030181-g001: Schematic Presentation of Transib transposons, RAG1, RAG2, and RAG1-Like Proteins in EukaryotesThe basic timescale of the evolutionary tree is based on published literature [49–51]. Red circles mark species in which Transib TPases were found. Gray squares indicate RAG2; orange and blue ellipses show the RAG1 core and RAG1 N-terminal domain, respectively. Overall taxonomy, including common and Latin names, is reported on the right side of the figure. A question mark at the lamprey lineage indicates insufficient sequence data. A lack of any labels means that the Transib TPase and RAG1/2 are not present in the sequenced portions of the corresponding genomes. Among branches lacking Transib TPases, only lamprey and crocodile genomes are not extensively sequenced to date. In sea anemone, the RAG1 core–like protein is capped by the ring finger motif, which also forms the C-terminus in the RAG1 N-terminal domain. In fungi, the Transib TPase was detected in soybean rust only.

Mentions: The Transib superfamily is one of ten superfamilies of DNA transposons detected so far in eukaryotes [17]. Like other DNA transposons, Transib transposons exist as autonomous and nonautonomous elements. The autonomous Transib transposons are 3–4 kb long and code for an approximately 700-aa TPase that is not similar to TPases from any other transposon superfamilies. Computational analysis of Transib elements, including their numerous insertions into copies of other transposons, demonstrated that Transib transposons are flanked by 5-bp target site duplications (TSDs), which also distinguishes this superfamily from all the others [17]. Transib transpositions are expected to be catalyzed by the binding of the TPase to TIRs of autonomous and nonautonomous transposons [17]. As discussed in this paper, in addition to the fruit fly (Drosophila melanogaster) and African malaria mosquito (Anopheles gambiae) genomes, in which Transib transposons were originally discovered, these genes are also present in diverse animals (Table S1), including other species of fruit fly (e.g., Drosophila pseudoobscura, Drosophila willistoni), yellow fever mosquito (Anopheles aegypti), silkworm (Bombyx mori), red flour beetle (Tribolium castaneum), dog hookworm (Ancylostoma caninum), freshwater flatworm (Schmidtea mediterranea), hydra (Hydra magnipapillata), sea urchin (Strongylocentrotus purpuratus), and soybean rust (Phakopsora pachyrhizi). Genomes of plants and vertebrates seem to be free of any recognizable Transib transposons (Figure 1).


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

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

Schematic Presentation of Transib transposons, RAG1, RAG2, and RAG1-Like Proteins in EukaryotesThe basic timescale of the evolutionary tree is based on published literature [49–51]. Red circles mark species in which Transib TPases were found. Gray squares indicate RAG2; orange and blue ellipses show the RAG1 core and RAG1 N-terminal domain, respectively. Overall taxonomy, including common and Latin names, is reported on the right side of the figure. A question mark at the lamprey lineage indicates insufficient sequence data. A lack of any labels means that the Transib TPase and RAG1/2 are not present in the sequenced portions of the corresponding genomes. Among branches lacking Transib TPases, only lamprey and crocodile genomes are not extensively sequenced to date. In sea anemone, the RAG1 core–like protein is capped by the ring finger motif, which also forms the C-terminus in the RAG1 N-terminal domain. In fungi, the Transib TPase was detected in soybean rust only.
© Copyright Policy
Related In: Results  -  Collection

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

pbio-0030181-g001: Schematic Presentation of Transib transposons, RAG1, RAG2, and RAG1-Like Proteins in EukaryotesThe basic timescale of the evolutionary tree is based on published literature [49–51]. Red circles mark species in which Transib TPases were found. Gray squares indicate RAG2; orange and blue ellipses show the RAG1 core and RAG1 N-terminal domain, respectively. Overall taxonomy, including common and Latin names, is reported on the right side of the figure. A question mark at the lamprey lineage indicates insufficient sequence data. A lack of any labels means that the Transib TPase and RAG1/2 are not present in the sequenced portions of the corresponding genomes. Among branches lacking Transib TPases, only lamprey and crocodile genomes are not extensively sequenced to date. In sea anemone, the RAG1 core–like protein is capped by the ring finger motif, which also forms the C-terminus in the RAG1 N-terminal domain. In fungi, the Transib TPase was detected in soybean rust only.
Mentions: The Transib superfamily is one of ten superfamilies of DNA transposons detected so far in eukaryotes [17]. Like other DNA transposons, Transib transposons exist as autonomous and nonautonomous elements. The autonomous Transib transposons are 3–4 kb long and code for an approximately 700-aa TPase that is not similar to TPases from any other transposon superfamilies. Computational analysis of Transib elements, including their numerous insertions into copies of other transposons, demonstrated that Transib transposons are flanked by 5-bp target site duplications (TSDs), which also distinguishes this superfamily from all the others [17]. Transib transpositions are expected to be catalyzed by the binding of the TPase to TIRs of autonomous and nonautonomous transposons [17]. As discussed in this paper, in addition to the fruit fly (Drosophila melanogaster) and African malaria mosquito (Anopheles gambiae) genomes, in which Transib transposons were originally discovered, these genes are also present in diverse animals (Table S1), including other species of fruit fly (e.g., Drosophila pseudoobscura, Drosophila willistoni), yellow fever mosquito (Anopheles aegypti), silkworm (Bombyx mori), red flour beetle (Tribolium castaneum), dog hookworm (Ancylostoma caninum), freshwater flatworm (Schmidtea mediterranea), hydra (Hydra magnipapillata), sea urchin (Strongylocentrotus purpuratus), and soybean rust (Phakopsora pachyrhizi). Genomes of plants and vertebrates seem to be free of any recognizable Transib transposons (Figure 1).

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