title: RAG Recombinase as a Selective Pressure for Genome Evolution.
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.
authors.affiliation: Instituto Gulbenkian de Ciência, Oeiras, Portugal.
authors.forename: D
authors.initials: D
authors.lastname: Passagem-Santos
authors.affiliation: Instituto Gulbenkian de Ciência, Oeiras, Portugal.
authors.forename: M
authors.initials: M
authors.lastname: Bonnet
authors.affiliation: Instituto Gulbenkian de Ciência, Oeiras, Portugal.
authors.forename: D
authors.initials: D
authors.lastname: Sobral
authors.affiliation: Instituto Gulbenkian de Ciência, Oeiras, Portugal.
authors.forename: I
authors.initials: I
authors.lastname: Trancoso
authors.affiliation: Instituto Gulbenkian de Ciência, Oeiras, Portugal.
authors.forename: J G
authors.initials: JG
authors.lastname: Silva
authors.affiliation: Instituto Gulbenkian de Ciência, Oeiras, Portugal.
authors.forename: V M
authors.initials: VM
authors.lastname: Barreto
authors.affiliation: Instituto Gulbenkian de Ciência, Oeiras, Portugal.
authors.forename: A
authors.initials: A
authors.lastname: Athanasiadis
authors.affiliation: Instituto Gulbenkian de Ciência, Oeiras, Portugal jleal@igc.gulbenkian.pt jocelyne@igc.gulbenkian.pt.
authors.forename: J
authors.initials: J
authors.lastname: Demengeot
authors.affiliation: Instituto Gulbenkian de Ciência, Oeiras, Portugal jleal@igc.gulbenkian.pt jocelyne@igc.gulbenkian.pt.
authors.forename: J B
authors.initials: JB
authors.lastname: Pereira-Leal
mesh_terms: D000818:Animals; D019143:Evolution, Molecular; D016678:Genome; D059372:Nucleotide Motifs; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA / Q000379:methods; D012984:Software; D045567:VDJ Recombinases / Q000235:genetics*; D014714:Vertebrates / Q000235:genetics
chemical_list: D045567:VDJ Recombinases
keywords: Bioinformatic RSS classifier; Cryptic RSS; Recombination Classifier; motif evolution