Heterozygosity at individual amino acid sites: Extremely high levels for HLA-A and -B genes

Philip W. Hedrick, Thomas S. Whittam, Peter Parham

Research output: Contribution to journalArticlepeer-review

93 Scopus citations


The amino acid heterozygosities per site for HLA-A and -B loci are determined to be extremely high by combining population serotypic frequencies with amino acid sequences. For the 54 amino acid sites thought to have functional importance, the average heterozygosity per site is 0.301. Sixteen positions have heterozygosities >0.5 at one or both loci and the frequencies of amino acids at a given position are very even, resulting in nearly the maximum heterozygosity possible. Furthermore, the high heterozygosity is concentrated in the peptide-interacting sites, whereas the sites that interact with the T-cell receptor have lower heterozygosity. Overall, these results indicate the importance of some form of balancing selection operating at HLA loci, maybe even at the individual amino acid level.

Original languageEnglish (US)
Pages (from-to)5897-5901
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number13
StatePublished - Jul 1 1991
Externally publishedYes


  • Evolution
  • Histocompatibility
  • Polymorphism

ASJC Scopus subject areas

  • General


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