Characterization of approximately 50 kb of the immunoglobulin VH locus of the Japanese pufferfish, Fugu rubripes

Abstract.

The variable region of the immunoglobulin heavy chain is created by a somatic rearrangement of a limited number of germline genes. This mechanism of gene assembly [V(D)J recombination] has been found to take place only in jawed vertebrates (gnathostomes). To understand how this mechanism evolved and diversified it is necessary to study the genomic organization of the heavy-chain gene in different vertebrate lineages. Since there is scant sequence information on the VH locus in fish, shotgun sequencing of a cosmid clone containing part of the VH genomic region of the Japanese pufferfish, Fugu rubripes, was undertaken. Eight full-length VH genes were isolated and characterized. They have higher homology to trout genes, but show the same structural features as VHs found in other vertebrates. Two VH subgroups have been identified whose members are interspersed. The frequency of synonymous and nonsynonymous substitution for VH comparisons between family members was found to be higher in the complementarity-determining regions than in the framework regions. Finally, there are four other genes interspersed with the VH genes, one of which is the first full-length retrotransposon element characterized in vertebrates.