Coevolution of immunoglobulin heavy- and light-chain variable-region gene families

The gene families encoding the immunoglobulin variable regions of heavy (V-H) and light (V-L) chains in vertebrates are composed of many genes. 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 variation and the evolutionary forces for these multigene families, we conducted a phylogenetic analysis of V-H and V-L genes from the species of 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, and, according to this clustering pattern, the species can be divided into two groups. In the first group of species (humans and mice), V-H and V-L genes were extensively intermingled with genes from other organisms; 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 multigene families have evolved in the same fashion: they have undergone coordinated 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 antibody variety. In humans and mice, DNA rearrangement of immunoglobulin 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 important roles. The evolutionary pattern of V-H and V-L multigene families is consistent with the birth-and-death model of evolution, yet different levels of diversifying selection seem to operate in the V-H and V-L genes of these two groups of species.