Molecular Biology and Evolution, Vol 6, 559-579, Copyright © 1989 by Society for Molecular Biology and Evolution
AL Hughes and M Nei
The class I major histocompatibility complex genes are composed of
classical and nonclassical genes, the latter being largely nonfunctional.
To understand the evolutionary relationships of the two groups of class I
genes, a phylogenetic analysis of DNA sequences was conducted using 45
genes from six mammalian and one avian species. The results indicate that
nonclassical genes in one species are more closely related to classical
genes from the same species than to nonclassical genes from a species
belonging to a different order or family. This indicates that the
differentiation of classical and nonclassical genes occurs rather rapidly
in the genome. Classical genes are apparently duplicated with a high
frequency in the evolutionary process, and many of the duplicated genes
seem to degenerate into nonclassical genes as a result of deleterious
mutation. The nonclassical Qa genes in the mouse have sequences homologous
to regulatory sequences involved in the universal expression of classical
class I genes, but they have accumulated numerous nucleotide substitutions
in these sequences. The pattern of nucleotide substitution in nonclassical
genes is different from that in classical genes. In nonclassical genes, the
rate of nonsynonymous substitution is higher in the antigen recognition
site than in other gene regions, as is true of classical genes. However,
unlike the case of classical genes, the nonsynonymous rate does not always
exceed the synonymous rate in the antigen recognition site. Nonclassical
proteins further differ from classical proteins in having amino acid
replacements in conserved antigen recognition site positions. These
observations are consistent with the hypothesis that nonclassical genes
have originated from classical genes but have lost classical class I
function because of deleterious mutation.
REVIEW ARTICLE
Evolution of the major histocompatibility complex: independent origin of nonclassical class I genes in different groups of mammals
Center for Demographic and Population Genetics, University of Texas Health Science Center, Houston 77225.
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