Evolution of the immunoglobulin heavy chain variable region (Igh-V) locus in the genus Mus

The evolution of the mouse immunoglobulin heavy chain variable region (Igh-V) locus was investigated by the comprehensive analysis of variable region (Vh) gene family content and restriction fragment polymorphism in the genus Mus. The examination of natural Mus domesticus populations suggests an important role for recombination in the generation of the considerable restriction fragment polymorphism found at the Igh-V locus. Although the sizes of individual Vh gene families vary widely both within and between different Mus species, evolutionary trends of Vh gene family copy number are revealed by the analysis of homologues of mouse Vh gene families in Rattus and Peromyscus. Processes of duplication, deletion, and sequence divergence all contribute to the evolution of Vh gene copy number. Certain Vh gene families have expanded or contracted differently in the various muroid lineages examined. Collectively, these findings suggest that the evolution of individual Vh family size is not driven by strong selective pressure but is relatively neutral, and that gene flow, rather than selection, serves to maintain the high level of restriction fragment polymorphism seen in M. domesticus.