DIVERGENT EVOLUTION AND EVOLUTION BY THE BIRTH-AND-DEATH PROCESS IN THE IMMUNOGLOBULIN V-H GENE FAMILY

Immunoglobulin diversity is generated primarily by the heavy- and ligh t-chain variable-region gene families. To understand the pattern of lo ng-term evolution of the heavy-chain variable-region (V-H) gene family , which is composed of a large number of member genes, the evolutionar y relationships of representative V-H genes from diverse organisms of vertebrates were studied by constructing a phylogenetic tree. This tre e indicates that the vertebrate V-H genes can be classified into group A, B, C, D, and E genes. All V-H genes from cartilaginous fishes such as sharks and skates form a monophyletic group and belong to group E, whereas group D consists of bony-fish V-H genes. By contrast, group C includes not only some fish genes but also amphibian, reptile, bird, and mammalian genes. Group A and B genes were composed of the genes fr om mammals and amphibians. The phylogenetic analysis also suggests tha t mammalian V-H genes are classified into three clusters-i.e., mammali an clans I, II, and III-and that these clans have coexisted in the gen ome for >400 Myr. To study the short-term evolution of V-H genes, the phylogenetic analysis of human group A (dan I) and C (dan III) genes w as also conducted. The results obtained show that V-H pseudogenes have evolved much faster than functional genes and that they have branched off from various functional V-H genes. There is little indication tha t the V-H gene family has been subject to concerted evolution that hom ogenizes member genes. These observations indicate that the V-H genes are subject to divergent evolution due to diversifying selection and e volution by the birth-and-death process caused by gene duplication and dysfunctioning mutation. Thus, the evolutionary pattern of this monof unctional multigene family is quite different from that of such gene f amilies as the ribosomal RNA and histone gene families.