Distinct patterns of IgH structure and organization in a divergent lineage of chrondrichthyan fishes

Abstract

 Immunoglobulin heavy chain (IgH) genes in representative chondrichthyan fishes (sharks and skates) consist of independently functioning clusters, containing separate variable (V _H ), diversity (D _H ), and joining (J _H ) region elements and constant (C _H ) region exons. IgH loci have been characterized in Hydrolagus colliei (spotted ratfish), a modern representative of a major independent chondrichthyan lineage. Three distinct families of IgH gene clusters were identified. The most numerous genes consist of unjoined V _H -D ₁ -D ₂ -J _H segments that correspond to the most abundant Hydrolagus spleen (cDNA) transcripts which apparently arise from a diversified gene family. In the second cluster type, V _H , D _H , and J _H segments are germline-joined, whereas the C _H exons exhibit typical organization. This gene type is found in only a few copies per haploid genome and both transmembrane and secretory transcripts have been identified. A third cluster type has been identified that consists of unjoined V _H elements but lacks a typical C _H 1 exon, which is substituted with a second C _H 2-like exon. Transcripts from this third cluster type also appear to derive from a diversified gene family. Genomic D regions of the two unjoined clone types exhibit structural differences that are consistent with incorporation of recombination machinery-mediated events. Genomic library screening indicates that 90% of V _H ⁺ clones are truncated, nearly identical pseudogenes (lacking J _H and C _H ). These studies demonstrate an early phylogenetic origin for the cluster type of gene organization and document extensive organizational diversification within an apparent single class of IgH genes.