EVOLUTION OF IMMUNOGLOBULIN V-H PSEUDOGENES IN CHICKENS

In chickens, there is a single functional gene (V(H)1) coding for the heavy chain variable region of immunoglobulins, and immunoglobulin div ersity is generated by gene conversion of the V(H)1 gene by many varia ble region pseudogenes (Psi V-H's) that exist on the 5' side of the V( H)1 gene. To understand the evolution of this unique genetic system, w e conducted statistical analyses of V(H)1 and Psi V-H genes together w ith functional V-H genes from other higher vertebrate species. The res ults indicate, first, that chicken V-H genes are all closely related t o one another and were derived relatively recently from an ancestral g ene belonging to one of the three major groups of V-H genes in higher vertebrates. Second, the rate of nonsynonymous substitution is slightl y higher than that of synonymous substitution in the complementarity-d etermining regions (CDRs), which suggests that diversity-enhancing sel ection has operated in the CDRs even for pseudogenes. However, both th e rates of synonymous and nonsynonymous substitution are higher in the CDRs than in the framework regions (FRs), apparently because of an in teraction between positive selection and meiotic gene conversion in th e CDRs. Third, a dot matrix analysis of the Psi V-H genes and genomic diversity (D) genes has indicated that the 3' end of Psi V-H genes is attached by D-gene-like sequences, and this region of Psi V-H genes ha s high similarity with D gene sequences. This suggests that V and D ge nes were fused at some point of evolutionary time and this fused eleme nt multiplied by gene duplication. Finally, two alternative hypotheses of explaining the evolution of the chicken V-H gene system are presen ted.