| To understand the diversity and evolution of the variable region (V) multigene families of T-cell receptors (TCR) and immunoglobulins (Ig) in vertebrates, the following four related studies were conducted. (1) I examined the diversity and evolution of TCR V genes in mammals and birds. I have shown that mammalian and avian genes intermingle extensively in the phylogenetic trees and can be classified into different gene groups. I found that humans and mice possess TCR V genes from almost all the groups, while other species lost the groups to different extents. This result is similar to that obtained for the Ig V genes and suggests that TCR and Ig V genes evolve in a coordinated fashion. (2) To investigate the evolutionary mechanism of the TCR V genes, I conducted a phylogenetic analysis of the complete genomic Vbeta (V region of beta chain) sequences from humans and mice. I found that the Vbeta gene regions have undergone frequent gene duplication and inactivation, and that the genes closely located in the genome do not necessarily cluster together in the phylogenetic tree. I presented evidence that the latter is caused by duplications involving a large DNA block rather than a single gene. In general, evolution of the Vbeta family is consistent with the birth-and-death model. (3) In rabbits, there is one Ig V locus (VH1) that is highly polymorphic. This polymorphism is also shared by the snowshoe hare. To understand the evolution of this trans-species polymorphism, I have estimated the persistence time of three polymorphic VH1 alleles and showed that these alleles have been maintained in the population for approximately 50 million years. (4) Camelids (camels and llamas) possess a novel type of Ig which is composed of two identical heavy chains only. To study the evolution of this "heavy-chain" Ig, I conducted a phylogenetic analysis of the V HH (V region in the heavy-chain Ig) genes from camels and llamas with the VH genes from mammals. I found that positive selection is operating on the antigen-binding regions of the VHH genes and that adaptive changes have occurred in the functionally important sites in the VHH genes. |
