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 light-chain variable-region gene families. To understand the pattern of long-term evolution of the heavy-chain variable-region (V-H) gene family, which is composed of a large number of member genes, the evolutionary relationships of representative V-H genes from diverse organisms of vertebrates were studied by constructing a phylogenetic tree. This tree 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 from mammals and amphibians. The phylogenetic analysis also suggests that mammalian V-H genes are classified into three clusters-i.e., mammalian clans I, II, and III-and that these clans have coexisted in the genome 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 was 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 that the V-H gene family has been subject to concerted evolution that homogenizes member genes. These observations indicate that the V-H genes are subject to divergent evolution due to diversifying selection and evolution by the birth-and-death process caused by gene duplication and dysfunctioning mutation. Thus, the evolutionary pattern of this monofunctional multigene family is quite different from that of such gene families as the ribosomal RNA and histone gene families.