Heavy-chain variable regions in carcharhine sharks: development of a comprehensive model for the evolution of VH domains among the gnathanstomes.

We determined the sequence of 18 DNA clones encoding VH regions of sandbar shark and bull shark. All of these sequences exhibit key structural coding features characteristic of known VH genes of higher vertebrates. These VH sequences disclosed considerable diversity, and can be divided into six families according to the criterion of 80% DNA sequence identity. The overlapping of some VH gene clones to two or more families is a particular feature found in carcharhine sharks, which suggests that VH diversification is a continuing process. The basic sequence patterns of heavy-chain V regions found in all representative gnathanstomes and in VH of the shark heavy immunoglobulin IgW provides evidence for selection of canonical residues in all VH structures. Elasmobranch VH sequences can be divided into two classes or clans, one comprising the 'classical' VH set and the other comprising VHS related to those of IgW (V omega). Phylogenetic analyses place the VH cluster as the root of all the classic VHS and indicates that the V omega set is most probably that of the primordial heavy chain.