Genetics, Vol. 156, 867-877, October 2000, Copyright © 2000

The Implications of Intergenic Polymorphism for Major Histocompatibility Complex Evolution

Colm O'hUigina, Yoko Sattab, Anja Hausmanna, Roger L. Dawkinsc, and Jan Kleina
a Max-Planck-Institut für Biologie, Abteilung Immungenetik, D-72076 Tübingen, Germany,
b Department for Biosystems Science, Graduate University for Advanced Studies, Hayama, Kanagawa 240-0193, Japan
c The Centre for Molecular Immunology and Instrumentation, The University of Western Australia, Perth, Australia

Corresponding author: Colm O'hUigin, Max-Planck-Institut für Biologie, Abt. Immungenetik, Corrensstr. 42, 72076 Tübingen, Germany., colm{at}tuebingen.mpg.de (E-mail)

Communicating editor: N. TAKAHATA

A systematic survey of six intergenic regions flanking the human HLA-B locus in eight haplotypes reveals the regions to be up to 20 times more polymorphic than the reported average degree of human neutral polymorphism. Furthermore, the extent of polymorphism is directly related to the proximity to the HLA-B locus. Apparently linkage to HLA-B locus alleles, which are under balancing selection, maintains the neutral polymorphism of adjacent regions. For these linked polymorphisms to persist, recombination in the 200-kb interval from HLA-B to TNF must occur at a low frequency. The high degree of polymorphism found distal to HLA-B suggests that recombination is uncommon on both sides of the HLA-B locus. The least-squares estimate is 0.15% per megabase with an estimated range from 0.02 to 0.54%. These findings place strong restrictions on possible recombinational mechanisms for the generation of diversity at the HLA-B.




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