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. 1989 Feb;86(3):958-62.
doi: 10.1073/pnas.86.3.958.

Nucleotide substitution at major histocompatibility complex class II loci: evidence for overdominant selection

A L Hughes  1 , M Nei
Affiliations

Nucleotide substitution at major histocompatibility complex class II loci: evidence for overdominant selection

A L Hughes et al. Proc Natl Acad Sci U S A. 1989 Feb.

Abstract

To study the mechanism of maintenance of polymorphism at major histocompatibility complex (MHC) loci, synonymous and nonsynonymous (amino acid-altering) nucleotide substitutions in the putative antigen-recognition site (included in the first domain of the MHC molecule) and other regions of human and mouse class II genes were examined. In the putative antigen-recognition site, the rate of nonsynonymous substitution was found to exceed that of synonymous substitution, whereas in the second domain the former was significantly lower than the latter. In light of a previous theoretical study and parallel findings in class I MHC loci, we conclude that the unusually high degree of polymorphism at class II MHC loci is caused mainly by overdominant selection (heterozygote advantage) operating in the antigen-recognition site.

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