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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 kappa chain V
region (V kappa) genes, phylogenetic analyses of V kappa genes from humans
and other vertebrate species were conducted. The results obtained indicate
that the V kappa 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 kappa genes and then the remaining two clusters
diverged. The mammalian V kappa genes can further be divided into 10 V
kappa groups, 7 of which are present in the human genome. Human and mouse V
kappa genes from different V kappa 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 kappa 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 kappa 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
kappa genes has been enhanced by positive Darwinian selection.
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