RAG Recombinase as a Selective Pressure for Genome Evolution

Detalhes bibliográficos
Autor(a) principal: Passagem-Santos, D.
Data de Publicação: 2016
Outros Autores: Bonnet, M., Sobral, D., Trancoso, I., Silva, J.G., Barreto, V.M., Athanasiadis, A., Demengeot, J., Pereira-Leal, J.B.
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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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
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