title: Structure and evolutionary history of a large family of NLR proteins in the zebrafish.
abstract: Multicellular eukaryotes have evolved a range of mechanisms for immune recognition. A widespread family involved in innate immunity are the NACHT-domain and leucine-rich-repeat-containing (NLR) proteins. Mammals have small numbers of NLR proteins, whereas in some species, mostly those without adaptive immune systems, NLRs have expanded into very large families. We describe a family of nearly 400 NLR proteins encoded in the zebrafish genome. The proteins share a defining overall structure, which arose in fishes after a fusion of the core NLR domains with a B30.2 domain, but can be subdivided into four groups based on their NACHT domains. Gene conversion acting differentially on the NACHT and B30.2 domains has shaped the family and created the groups. Evidence of positive selection in the B30.2 domain indicates that this domain rather than the leucine-rich repeats acts as the pathogen recognition module. In an unusual chromosomal organization, the majority of the genes are located on one chromosome arm, interspersed with other large multigene families, including a new family encoding zinc-finger proteins. The NLR-B30.2 proteins represent a new family with diversity in the specific recognition module that is present in fishes in spite of the parallel existence of an adaptive immune system.
authors.affiliation: Wellcome Trust Sanger Institute, Cambridge, UK.
authors.forename: Kerstin
authors.identifier: http://orcid.org/0000-0003-2237-513X
authors.initials: K
authors.lastname: Howe
authors.affiliation: Institut für Genetik, Universität zu Köln, Köln, Germany The European Molecular Biology Laboratory, Heidelberg, Germany.
authors.forename: Philipp H
authors.identifier: http://orcid.org/0000-0001-6776-0934
authors.initials: PH
authors.lastname: Schiffer
authors.affiliation: Institut für Genetik, Universität zu Köln, Köln, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Zielinski
authors.affiliation: Institut für Genetik, Universität zu Köln, Köln, Germany.
authors.forename: Thomas
authors.identifier: http://orcid.org/0000-0002-8932-2772
authors.initials: T
authors.lastname: Wiehe
authors.affiliation: Wellcome Trust Sanger Institute, Cambridge, UK.
authors.forename: Gavin K
authors.identifier: http://orcid.org/0000-0003-2294-0135
authors.initials: GK
authors.lastname: Laird
authors.affiliation: Wellcome Trust Sanger Institute, Cambridge, UK The European Molecular Biology Laboratory, The European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, UK.
authors.forename: John C
authors.identifier: http://orcid.org/0000-0001-9092-0852
authors.initials: JC
authors.lastname: Marioni
authors.affiliation: Bioinformatics and Genomics Programme, Centre for Genomic Regulation (CRG) 88 Dr. Aiguader, 08003 Barcelona, Spain Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain.
authors.forename: Onuralp
authors.identifier: http://orcid.org/0000-0001-8308-6855
authors.initials: O
authors.lastname: Soylemez
authors.affiliation: Bioinformatics and Genomics Programme, Centre for Genomic Regulation (CRG) 88 Dr. Aiguader, 08003 Barcelona, Spain Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain Institució Catalana de Recerca i Estudis Avançats (ICREA), 23 Pg. Lluís Companys, 08010 Barcelona, Spain.
authors.forename: Fyodor
authors.initials: F
authors.lastname: Kondrashov
authors.affiliation: Institut für Genetik, Universität zu Köln, Köln, Germany The European Molecular Biology Laboratory, Heidelberg, Germany mleptin@uni-koeln.de.
authors.forename: Maria
authors.identifier: http://orcid.org/0000-0001-7097-348X
authors.initials: M
authors.lastname: Leptin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D019143:Evolution, Molecular; D016678:Genome; D005810:Multigene Family; D000070576:NLR Proteins / Q000737:chemistry* / Q000235:genetics*; D000072417:Protein Domains; D013997:Time Factors; D015027:Zebrafish / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000737:chemistry* / Q000235:genetics*
chemical_list: D000070576:NLR Proteins; D029961:Zebrafish Proteins
keywords: B30.2; NACHT; SPRY; gene conversion; genome evolution; innate immune system