Resolution of the Novel Immune-Type Receptor Gene Cluster in Zebrafish

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 101; no. 44; pp. 15706 - 15711
• Main Authors: Yoder, Jeffrey A., Litman, Ronda T., Mueller, M. Gail, Desai, Salil, Dobrinski, Kimberly P., Montgomery, Jennifer S., Buzzeo, Matthew P., Ota, Tatsuya, Amemiya, Chris T., Trede, Nikolaus S., Wei, Sheng, Djeu, Julie Y., Humphray, Sean, Jekosch, Kerstin, Jose A. Hernandez Prada, Ostrov, David A., Litman, Gary W., Herzenberg, Leonard A.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 02-11-2004; National Acad Sciences
• Subjects: Alleles; Alternative Splicing; Amino Acid Sequence; Animals; Biological Sciences; Cells; Chromosome Mapping; Chromosomes; Complementary DNA; Danio rerio; DNA, Complementary - genetics; Evolution, Molecular; Fish; Freshwater; Genes; Genetic Variation; Genomes; Genomics; Immunology; Lectins; Lectins, C-Type - chemistry; Lectins, C-Type - genetics; Leukocytes; Models, Molecular; Molecular Sequence Data; Multigene Family; Phylogeny; Protein Structure, Tertiary; Receptors; Receptors, Immunologic - chemistry; Receptors, Immunologic - genetics; Sequencing; Zebrafish - genetics; Zebrafish - immunology; Zebrafish Proteins - chemistry; Zebrafish Proteins - genetics; Zebrafish Proteins - immunology
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0405242101

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 ≈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.