Computer simulation analysis suggests weak balancing selection operative at the MICA locus

A high degree of polymorphism has been reported at the major histocompatibi lity class I chain-related gene A (MICA) locus, which is located 46 kb away from HLA-Bin the human major histocompatibility complex (MHC) class I regi on. Although it is known that the polymorphisms at the conventional MHC cla ss I loci have been maintained by balancing selection, it is unclear whethe r positive natural selection is also operative in maintaining the polymorph ism at the MICA locus. In order to explain the degree of polymorphism at th e MICA locus, a computer simulation study was carried out. The high degree of polymorphism at the MICA locus (heterozygosity and number of polymorphic residues) could not be explained solely by balancing selection at the HLA- B locus even if no recombination was assumed between MICA and HLA-B, Althou gh there is no definite evidence indicating that balancing selection is ope rative at the MICA locus, our results suggest that the MICA gene is subject to weak balancing selection.