Contrasting roles of interallelic recombination at the HLA-A and HLA-B loci

A. L. Hughes, M. K. Hughes, David Watkins

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

A statistical study of DNA sequences of alleles at the highly polymorphic class I MHC loci of humans, HLA-A and HLA-B, showed evidence of both large- scale recombination events (involving recombination of exons 1-2 of one allele with exons 3-8 of another) and small-scale recombination events (involving apparent exchange of short DNA segments). The latter events occurred disproportionately in the region of the gene encoding the antigen recognition site (ARS) of the class I molecule. Furthermore, they involved the ARS codons which are under the strongest selection favoring allelic diversity at the amino acid level. Thus, the frequency of recombinant alleles appears to have been increased by some form of balancing selection (such as overdominant selection) favoring heterozygosity in the ARS. These analyses also revealed a striking difference between the A and B loci. Recombination events appear to have occurred about twice as frequently at the B locus, and recombinants at the B locus were significantly more likely to affect polymorphic sites in the ARS. At the A locus, there are well-defined allelic lineages that have persisted since prior to the human-chimpanzee divergence; but at the B locus, there is no evidence for such long-lasting allelic lineages. Thus, relatively frequent interallelic recombination has apparently been a feature of the long-term evolution of the B locus but not of the A locus.

Original languageEnglish
Pages (from-to)669-680
Number of pages12
JournalGenetics
Volume133
Issue number3
StatePublished - Jan 1 1993
Externally publishedYes

Fingerprint

HLA-A Antigens
HLA-B Antigens
Genetic Recombination
Antigens
Exons
Alleles
Pan troglodytes
Gene Frequency
Codon
Amino Acids
DNA
Genes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Contrasting roles of interallelic recombination at the HLA-A and HLA-B loci. / Hughes, A. L.; Hughes, M. K.; Watkins, David.

In: Genetics, Vol. 133, No. 3, 01.01.1993, p. 669-680.

Research output: Contribution to journalArticle

Hughes, AL, Hughes, MK & Watkins, D 1993, 'Contrasting roles of interallelic recombination at the HLA-A and HLA-B loci', Genetics, vol. 133, no. 3, pp. 669-680.
Hughes, A. L. ; Hughes, M. K. ; Watkins, David. / Contrasting roles of interallelic recombination at the HLA-A and HLA-B loci. In: Genetics. 1993 ; Vol. 133, No. 3. pp. 669-680.
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