Evolution of immunoglobulin kappa chain variable region genes in vertebrates

Abstract

The major source of immunoglobulin diversity is variation in DNA sequence among multiple copies of variable region (V) genes of the heavy- and light-chain multigene families. In order to clarify the evolutionary pattern of the multigene family of immunoglobulin light K chain V region (V(k)) genes, phylogenetic analyses of V(K), genes from humans and other vertebrate species were conducted. The results obtained indicate that the V(K) genes so far sequenced can be grouped into three major monophyletic clusters, the cartilaginous fish, bony fish and amphibian, and mammalian clusters, and that the cartilaginous fish cluster first separated from the rest of the V(K) genes and then the remaining two clusters diverged. The mammalian V(K) genes can further be divided into 10 V(K) groups, 7 of which are present in the human genome. Human and mouse V(K) genes from different V(K) groups are intermingled rather than clustered on the chromosome, and there are a large number of pseudogenes scattered on the chromosome. This indicates that the chromosomal locations of V(K) genes have been shuffled many times by gene duplication, deletion, and transposition in the evolutionary process and that many genes have become nonfunctional during this process. This mode of evolution is consistent with the model of birth-and-death evolution rather than with the model of concerted evolution. An analysis of duplicate V(K) functional genes and pseudogenes in the human genome has indicated that pseudogenes evolve faster than functional genes but that the rate of nonsynonymous nucleotide substitution in the complementarity-determining regions of V(K) genes has been enhanced by positive Darwinian selection.