title: Resolution of the novel immune-type receptor gene cluster in zebrafish.
abstract: The novel immune-type receptor (NITR) genes encode a unique multigene family of leukocyte regulatory receptors, which possess an extracellular Ig variable (V) domain and may function in innate immunity. Artificial chromosomes that encode zebrafish NITRs have been assembled into a contig spanning approximately 350 kb. Resolution of the complete NITR gene cluster has led to the identification of eight previously undescribed families of NITRs and has revealed the presence of C-type lectins within the locus. A maximum haplotype of 36 NITR genes (138 gene sequences in total) can be grouped into 12 distinct families, including inhibitory and activating receptors. An extreme level of interindividual heterozygosity is reflected in allelic polymorphisms, haplotype variation, and family-specific isoform complexity. In addition, the exceptional diversity of NITR sequences among species suggests divergent evolution of this multigene family with a birth-and-death process of member genes. High-confidence modeling of Nitr V-domain structures reveals a significant shift in the spatial orientation of the Ig fold, in the region of highest interfamily variation, compared with Ig V domains. These studies resolve a complete immune gene cluster in zebrafish and indicate that the NITRs represent the most complex family of activating/inhibitory surface receptors thus far described.
authors.affiliation: Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, NC 27606, USA.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Yoder
authors.forename: Ronda T
authors.initials: RT
authors.lastname: Litman
authors.forename: M Gail
authors.initials: MG
authors.lastname: Mueller
authors.forename: Salil
authors.initials: S
authors.lastname: Desai
authors.forename: Kimberly P
authors.initials: KP
authors.lastname: Dobrinski
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Montgomery
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Buzzeo
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Ota
authors.forename: Chris T
authors.initials: CT
authors.lastname: Amemiya
authors.forename: Nikolaus S
authors.initials: NS
authors.lastname: Trede
authors.forename: Sheng
authors.initials: S
authors.lastname: Wei
authors.forename: Julie Y
authors.initials: JY
authors.lastname: Djeu
authors.forename: Sean
authors.initials: S
authors.lastname: Humphray
authors.forename: Kerstin
authors.initials: K
authors.lastname: Jekosch
authors.forename: Jose A
authors.initials: JA
authors.lastname: Hernandez Prada
authors.forename: David A
authors.initials: DA
authors.lastname: Ostrov
authors.forename: Gary W
authors.initials: GW
authors.lastname: Litman
mesh_terms: D000483:Alleles; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D002874:Chromosome Mapping; D018076:DNA, Complementary / Q000235:genetics; D019143:Evolution, Molecular; D014644:Genetic Variation; D037181:Lectins, C-Type / Q000737:chemistry / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D005810:Multigene Family; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D011971:Receptors, Immunologic / Q000737:chemistry / Q000235:genetics*; D015027:Zebrafish / Q000235:genetics* / Q000276:immunology*; D029961:Zebrafish Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology
chemical_list: D018076:DNA, Complementary; D037181:Lectins, C-Type; D011971:Receptors, Immunologic; D029961:Zebrafish Proteins