title: Diverse organization of immunoglobulin VH gene loci in a primitive vertebrate.
abstract: The immunoglobulin (Ig) heavy chain variable (VH) gene family of Heterodontus francisci (horned shark), a phylogenetically distant vertebrate, is unique in that VH, diversity (DH), joining (JH) and constant region (CH) gene segments are linked closely, in multiple individual clusters. The V regions of 12 genomic (liver and gonad) DNA clones have been sequenced completely and three organization patterns are evident: (i) VH-D1-D2-JH-CH with unique 12/22 and 12/12 spacers in the respective D recombination signal sequences (RSSs); VH and JH segments have 23 nucleotide (nt) spacers, (ii) VHDH-JH-CH, an unusual germline configuration with joined VH and DH segments and (iii) VHDHJH-CH, with all segmental elements being joined. The latter two configurations do not appear to be pseudogenes. Another VH-D1-D2-JH-CH gene possesses a D1 segment that is flanked by RSSs with 12 nt spacers and a D2 segment with 22/12 spacers. Based on the comparison of spleen, VH+ cDNA sequences to a germline consensus, it is evident that both DH segments as well as junctional and N-type diversity account for Ig variability. In this early vertebrate, the Ig genes share unique properties with higher vertebrate T-cell receptor as well as with Ig and may reflect the structure of a common ancestral antigen binding receptor gene.
authors.affiliation: Showa University Research Institute, St Petersburg, FL 33716.
authors.forename: F
authors.initials: F
authors.lastname: Kokubu
authors.forename: R
authors.initials: R
authors.lastname: Litman
authors.forename: M J
authors.initials: MJ
authors.lastname: Shamblott
authors.forename: K
authors.initials: K
authors.lastname: Hinds
authors.forename: G W
authors.initials: GW
authors.lastname: Litman
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D005075:Biological Evolution; D015139:Blotting, Southern; D004247:DNA / Q000235:genetics*; D015342:DNA Probes; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D008969:Molecular Sequence Data; D005810:Multigene Family; D009693:Nucleic Acid Hybridization; D015183:Restriction Mapping; D012754:Sharks / Q000235:genetics*
chemical_list: D015342:DNA Probes; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D004247:DNA