Evolutionary Genetics of the Major Histocompatibility Complex

The major histocompatibility complex (MHC) is becoming one of the most thoroughly investigated regions in vertebrate genomes. This region was first studied because of its importance in tissue transplantation and the immune system in humans. Now there is detailed genetic knowledge on many of the over 80 genes in the MHC, both about the extent and pattern of genetic variation in this region and about the molecular structure and functions of the molecules coded by its genes. For example, the level of amino acid heterozygosity is often extremely high, reaching over 60% at some amino acid sites with primary immune function (i.e., those involved with presenting peptides to the T-cell receptor). The frequency distribution of alleles at many of the loci in this region is quite even, and, in some populations, there is an observed deficiency of homozygotes. These and other observations point to the importance of some type of balancing selection operating in this region. It is generally assumed that this selection is related to the basic role of the MHC as part of the vertebrate immune system acting to prevent attack by viruses, bacteria, and other parasites. In addition, research suggests that there is selection at the MHC involved with maternal-fetal interactions and nonrandom mating. As a result of our detailed understanding of this region and its obvious selective importance, it now can be considered another classic example of an adaptive polymorphism, one that may be used as an evolutionary genetic paradigm.