EVOLUTION OF IMMUNOGLOBULIN-KAPPA CHAIN VARIABLE REGION GENES IN VERTEBRATES

The major source of immunoglobulin diversity is variation in DNA seque nce among multiple copies of variable region (V) genes of the heavy- a nd light-chain multigene families. In order to clarify the evolutionar y pattern of the multigene family of immunoglobulin light kappa chain V region (V-kappa) genes, phylogenetic analyses of V-kappa genes from humans and other vertebrate species were conducted. The results obtain ed indicate that the V-kappa genes so far sequenced can be grouped int o three major monophyletic clusters, the cartilaginous fish, bony fish and amphibian, and mammalian clusters, and that the cartilaginous fis h cluster first separated from the rest of the V-kappa genes and then the remaining two clusters diverged. The mammalian V-kappa genes can f urther be divided into 10 V-kappa groups, 7 of which are present in th e human genome. Human and mouse V-kappa genes from different V-kappa g roups are intermingled rather than clustered on the chromosome, and th ere are a large number of pseudogenes scattered on the chromosome. Thi s indicates that the chromosomal locations of V-kappa genes have been shuffled many times by gene duplication, deletion, and transposition i n the evolutionary process and that many genes have become nonfunction al during this process. This mode of evolution is consistent with the model of birth-and-death evolution rather than with the model of conce rted evolution. An analysis of duplicate V-kappa functional genes and pseudogenes in the human genome has indicated that pseudogenes evolve faster than functional genes but that the rate of nonsynonymous nucleo tide substitution in the complementarity-determining regions of V-kapp a genes has been enhanced by positive Darwinian selection.