RAG Recombinase as a Selective Pressure for Genome Evolution

Passagem-Santos, D.; Bonnet, M.; Sobral, D.; Trancoso, I.; Silva, J.G.; Barreto, V.M.; Athanasiadis, A.; Demengeot, J.; Pereira-Leal, J.B.

Publication

RAG Recombinase as a Selective Pressure for Genome Evolution

2016-12-14Journal article

dc.contributor.author	Passagem-Santos, D.
dc.contributor.author	Bonnet, M.
dc.contributor.author	Sobral, D.
dc.contributor.author	Trancoso, I.
dc.contributor.author	Silva, J.G.
dc.contributor.author	Barreto, V.M.
dc.contributor.author	Athanasiadis, A.
dc.contributor.author	Demengeot, J.
dc.contributor.author	Pereira-Leal, J.B.
dc.date.accessioned	2017-01-13T11:43:25Z
dc.date.available	2017-01-13T11:43:25Z
dc.date.issued	2016-12-14
dc.description.abstract	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.	pt_PT
dc.description.sponsorship	Instituto Gulbenkian de Ciência; Optimus alive award; Fundação para a Ciência e Tecnologia grant: (SFRH/BPD/65292/2009).	pt_PT
dc.description.version	info:eu-repo/semantics/publishedVersion	pt_PT
dc.identifier.citation	D. Passagem-Santos, M. Bonnet, D. Sobral, I. Trancoso, J.G. Silva, V.M. Barreto, A. Athanasiadis, J. Demengeot, and J.B. Pereira-Leal RAG Recombinase as a Selective Pressure for Genome Evolution Genome Biol Evol (2016) Vol. 8 3364-3376 first published online November 9, 2016 doi:10.1093/gbe/evw261	pt_PT
dc.identifier.doi	10.1093/gbe/evw261	pt_PT
dc.identifier.uri	http://hdl.handle.net/10400.7/728
dc.language.iso	eng	pt_PT
dc.peerreviewed	yes	pt_PT
dc.publisher	Oxford University Press	pt_PT
dc.relation.publisherversion	http://gbe.oxfordjournals.org/content/8/11/3364.long#sec-1	pt_PT
dc.rights.uri	http://creativecommons.org/licenses/by-nc/4.0/	pt_PT
dc.subject	Bioinformatic RSS classifier	pt_PT
dc.subject	Cryptic RSS	pt_PT
dc.subject	motif evolution	pt_PT
dc.subject	Recombination Classifier	pt_PT
dc.title	RAG Recombinase as a Selective Pressure for Genome Evolution	pt_PT
dc.type	journal article
dspace.entity.type	Publication
oaire.awardURI	info:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FBIA-GEN%2F116830%2F2010/PT
oaire.awardURI	info:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBD%2F51179%2F2010/PT
oaire.citation.endPage	3376	pt_PT
oaire.citation.issue	11	pt_PT
oaire.citation.startPage	3364	pt_PT
oaire.citation.title	Genome Biology and Evolution	pt_PT
oaire.citation.volume	8	pt_PT
oaire.fundingStream	3599-PPCDT
oaire.fundingStream	SFRH
project.funder.identifier	http://doi.org/10.13039/501100001871
project.funder.identifier	http://doi.org/10.13039/501100001871
project.funder.name	Fundação para a Ciência e a Tecnologia
project.funder.name	Fundação para a Ciência e a Tecnologia
rcaap.rights	openAccess	pt_PT
rcaap.type	article	pt_PT
relation.isProjectOfPublication	210a45bb-0e47-4205-913a-112af5d6ea85
relation.isProjectOfPublication	3052cda2-485d-4323-ad70-20a562c58e35
relation.isProjectOfPublication.latestForDiscovery	210a45bb-0e47-4205-913a-112af5d6ea85