COEVOLUTION OF IMMUNOGLOBULIN HEAVY-CHAIN AND LIGHT-CHAIN VARIABLE-REGION GENE FAMILIES

The gene families encoding the immunoglobulin variable regions of heav y (V-H) and light (V-L) chains in vertebrates are composed of many gen es. However, the gene number and the extent of diversity among V-H and V-L gene copies vary with species. To examine the causes of this vari ation and the evolutionary forces for these multigene families, we con ducted a phylogenetic analysis of V-H and V-L genes from the species o f amniotes. The results of our analysis showed that for each species, V-H and V-L genes have the same pattern of clustering in the trees, an d, according to this clustering pattern, the species can be divided in to two groups. In the first group of species (humans and mice), V-H an d V-L genes were extensively intermingled with genes from other organi sms; in the second group of species (chickens, rabbits, cattle, sheep, swine, and horses), the genes tended to form clusters within the same group of organisms. These results suggest that the V-H and V-L multig ene families have evolved in the same fashion: they have undergone coo rdinated contraction and expansion of gene repertoires such that each group of organisms is characterized by a certain level of diversity of V-H and V-L genes. The extent of diversity among copies of V-H and V- L genes in each species is related to the mechanism of generation of a ntibody variety. In humans and mice, DNA rearrangement of immunoglobul in variable, diversity, and joining-segment genes is a main source of antibody diversity, whereas in chickens, rabbits, cattle, sheep, swine , and horses, somatic hypermutation and somatic gene conversion play i mportant roles. The evolutionary pattern of V-H and V-L multigene fami lies is consistent with the birth-and-death model of evolution, yet di fferent levels of diversifying selection seem to operate in the V-H an d V-L genes of these two groups of species.