Evolution at HLA: possible explanations for the deficiency of homozygotes in two populations

There is substantial evidence that some form of balancing selection is important for loci in the HLA region. Two classic studies found a large deficiency of homozygotes for these loci. Four possible proposed selective explanations were proposed: (1) heterozygous advantage; (2) linked lethal; (3) maternal-fetal interaction, and (4) resistance to infectious disease. These hypotheses as well as another explanation, different male and female gametic frequencies, have been examined here to try and evaluate their potential impact on genotypic frequencies. For any of these selective mechanisms to alone account for the observed homozygous deficiency, selection and/or others factors would have to be extremely strong. The linked lethal selection model and the hypothesis based on different male and female gametic frequencies appear to be unlikely explanations for these observations. Other factors that may influence genotypic frequencies are also discussed.