RAG Recombinase as a Selective Pressure for Genome Evolution
Autor(a) principal: | |
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Data de Publicação: | 2016 |
Outros Autores: | , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.7/728 |
Resumo: | The RAG recombinase is a domesticated transposable element co-opted in jawed vertebrates to drive the process of the so-called V(D)J recombination, which is the hallmark of the adaptive immune system to produce antigen receptors. RAG targets, namely, the Recombination Signal Sequences (RSS), are rather long and degenerated sequences, which highlights the ability of the recombinase to interact with a wide range of target sequences, including outside of antigen receptor loci. The recognition of such cryptic targets by the recombinase threatens genome integrity by promoting aberrant DNA recombination, as observed in lymphoid malignancies. Genomes evolution resulting from RAG acquisition is an ongoing discussion, in particular regarding the counter-selection of sequences resembling the RSS and the modifications of epigenetic regulation at these potential cryptic sites. Here, we describe a new bioinformatics tool to map potential RAG targets in all jawed vertebrates. We show that our REcombination Classifier (REC) outperforms the currently available tool and is suitable for full genomes scans from species other than human and mouse. Using the REC, we document a reduction in density of potential RAG targets at the transcription start sites of genes co-expressed with the rag genes and marked with high levels of the trimethylation of the lysine 4 of the histone 3 (H3K4me3), which correlates with the retention of functional RAG activity after the horizontal transfer. |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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7160 |
spelling |
RAG Recombinase as a Selective Pressure for Genome EvolutionBioinformatic RSS classifierCryptic RSSmotif evolutionRecombination ClassifierThe RAG recombinase is a domesticated transposable element co-opted in jawed vertebrates to drive the process of the so-called V(D)J recombination, which is the hallmark of the adaptive immune system to produce antigen receptors. RAG targets, namely, the Recombination Signal Sequences (RSS), are rather long and degenerated sequences, which highlights the ability of the recombinase to interact with a wide range of target sequences, including outside of antigen receptor loci. The recognition of such cryptic targets by the recombinase threatens genome integrity by promoting aberrant DNA recombination, as observed in lymphoid malignancies. Genomes evolution resulting from RAG acquisition is an ongoing discussion, in particular regarding the counter-selection of sequences resembling the RSS and the modifications of epigenetic regulation at these potential cryptic sites. Here, we describe a new bioinformatics tool to map potential RAG targets in all jawed vertebrates. We show that our REcombination Classifier (REC) outperforms the currently available tool and is suitable for full genomes scans from species other than human and mouse. Using the REC, we document a reduction in density of potential RAG targets at the transcription start sites of genes co-expressed with the rag genes and marked with high levels of the trimethylation of the lysine 4 of the histone 3 (H3K4me3), which correlates with the retention of functional RAG activity after the horizontal transfer.Oxford University PressARCAPassagem-Santos, D.Bonnet, M.Sobral, D.Trancoso, I.Silva, J.G.Barreto, V.M.Athanasiadis, A.Demengeot, J.Pereira-Leal, J.B.2017-01-13T11:43:25Z2016-12-142016-12-14T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.7/728eng10.1093/gbe/evw261info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-11-21T14:18:50Zoai:arca.igc.gulbenkian.pt:10400.7/728Portal AgregadorONGhttps://www.rcaap.pt/oai/openairemluisa.alvim@gmail.comopendoar:71602024-11-21T14:18:50Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
RAG Recombinase as a Selective Pressure for Genome Evolution |
title |
RAG Recombinase as a Selective Pressure for Genome Evolution |
spellingShingle |
RAG Recombinase as a Selective Pressure for Genome Evolution Passagem-Santos, D. Bioinformatic RSS classifier Cryptic RSS motif evolution Recombination Classifier |
title_short |
RAG Recombinase as a Selective Pressure for Genome Evolution |
title_full |
RAG Recombinase as a Selective Pressure for Genome Evolution |
title_fullStr |
RAG Recombinase as a Selective Pressure for Genome Evolution |
title_full_unstemmed |
RAG Recombinase as a Selective Pressure for Genome Evolution |
title_sort |
RAG Recombinase as a Selective Pressure for Genome Evolution |
author |
Passagem-Santos, D. |
author_facet |
Passagem-Santos, D. Bonnet, M. Sobral, D. Trancoso, I. Silva, J.G. Barreto, V.M. Athanasiadis, A. Demengeot, J. Pereira-Leal, J.B. |
author_role |
author |
author2 |
Bonnet, M. Sobral, D. Trancoso, I. Silva, J.G. Barreto, V.M. Athanasiadis, A. Demengeot, J. Pereira-Leal, J.B. |
author2_role |
author author author author author author author author |
dc.contributor.none.fl_str_mv |
ARCA |
dc.contributor.author.fl_str_mv |
Passagem-Santos, D. Bonnet, M. Sobral, D. Trancoso, I. Silva, J.G. Barreto, V.M. Athanasiadis, A. Demengeot, J. Pereira-Leal, J.B. |
dc.subject.por.fl_str_mv |
Bioinformatic RSS classifier Cryptic RSS motif evolution Recombination Classifier |
topic |
Bioinformatic RSS classifier Cryptic RSS motif evolution Recombination Classifier |
description |
The RAG recombinase is a domesticated transposable element co-opted in jawed vertebrates to drive the process of the so-called V(D)J recombination, which is the hallmark of the adaptive immune system to produce antigen receptors. RAG targets, namely, the Recombination Signal Sequences (RSS), are rather long and degenerated sequences, which highlights the ability of the recombinase to interact with a wide range of target sequences, including outside of antigen receptor loci. The recognition of such cryptic targets by the recombinase threatens genome integrity by promoting aberrant DNA recombination, as observed in lymphoid malignancies. Genomes evolution resulting from RAG acquisition is an ongoing discussion, in particular regarding the counter-selection of sequences resembling the RSS and the modifications of epigenetic regulation at these potential cryptic sites. Here, we describe a new bioinformatics tool to map potential RAG targets in all jawed vertebrates. We show that our REcombination Classifier (REC) outperforms the currently available tool and is suitable for full genomes scans from species other than human and mouse. Using the REC, we document a reduction in density of potential RAG targets at the transcription start sites of genes co-expressed with the rag genes and marked with high levels of the trimethylation of the lysine 4 of the histone 3 (H3K4me3), which correlates with the retention of functional RAG activity after the horizontal transfer. |
publishDate |
2016 |
dc.date.none.fl_str_mv |
2016-12-14 2016-12-14T00:00:00Z 2017-01-13T11:43:25Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.7/728 |
url |
http://hdl.handle.net/10400.7/728 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
10.1093/gbe/evw261 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Oxford University Press |
publisher.none.fl_str_mv |
Oxford University Press |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
mluisa.alvim@gmail.com |
_version_ |
1817549557455650816 |