The nucleotide diversity of MICA and MICB suggests the effect of overdominant selection

The major histocompatibility complex (MHC) class I-related molecules A and B (MICA and MICB) are stress-inducible cell surface antigens that are recognized by immunocytes bearing the receptor NKG2D. In our study we estimated the average number of synonymous (pis) and nonsynonymous nucleotide substitutions (pia) per site in exons 2-4 of MICA and MICB. In exons 2 and 3 of MICB only nonsynonymous substitutions were found, and in exon 3 of MICA pia clearly exceeded pis. This finding is in contrast to the evolutionary parameters found in most other genes, and is reminiscent of the elevated pia values caused by overdominant selection in the peptide-binding region of conventional MHC class I molecules. It may be explained by the hypothetical interaction with nonpeptide antigens, or by resistance against pathogens.