Molecular Biology and Evolution, Vol 1, 195-212, Copyright © 1984 by Society for Molecular Biology and Evolution
T Gojobori and M Nei
With the aim of understanding the concerted evolution of the immunoglobulin
VH multigene family, a phylogenetic tree for the DNA sequences of 16 mouse
and five human germ line genes was constructed. This tree indicates that
all genes in this family have undergone substantial evolutionary
divergence. The most closely related genes so far identified in the mouse
genome seem to have diverged about 6 million years (MY) ago, whereas the
most distantly related genes diverged about 300 MY ago. This suggests that
gene duplication caused by unequal crossing-over or gene conversion occurs
very slowly in this gene family. The rate of occurrence of gene duplication
in the VH gene family has been estimated to be 5 x 10(-7) per gene per
year, which seems to be at least about 100 times lower than that for the
rRNA gene family. This low rate of concerted evolution in the VH gene
family helps retain intergenic genetic variability that in turn contributes
to antibody diversity. Because of accumulation of destructive mutations,
however, about one-third of the mouse and human VH genes seem to have
become nonfunctional. Many of these pseudogenes have apparently originated
recently, but some of them seem to have existed in the genome for more than
10 MY. The rate of nucleotide substitution for the
complementarity-determining regions (CDRs) is as high as that of
pseudogenes. This suggests that there is virtually no purifying selection
operating in the CDRs and that germ line mutations are effectively used for
generating antibody diversity.
ORIGINAL ARTICLE
Concerted evolution of the immunoglobulin VH gene family
University of Texas, Houston.
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