H-2 Antigens pp 89-102 | Cite as

Can Heterozygote Advantage Account for the Maintenance of H-2 Polymorphisms

  • Wayne K. Potts
  • C. Jo Manning
  • Ammon B. Peck
  • Marjorie Price-LaFace
  • Edward K. Wakeland
Part of the NATO ASI Series book series (NSSA, volume 144)


Discovering the forces that maintain the extreme polymorphisms found at loci within the major histocompatibility complex (MHC) is critical to understanding the role of MHC gene products in nature. It is often assumed that MHC polymorphisms are maintained in natural populations by heterozygote advantage. The feasibility of this assumption is examined by applying population genetics models developed by Sewall Wright to relevant parameters for the MHC of Mus musculus (H-2). The parameters that affect the number of alleles that can be maintained (assuming random mating) are effective population size (Ne), mutation rate (p), and the selection against homozygotes relative to heterozygotes (s). The number of alleles that can be maintained for various combinations of Ne, p, and s are presented graphically. Even with extreme parameter values maximizing the number of alleles at equilibrium (Ne=100, p=10−4, s=1) only about seven alleles can be maintained within local populations. More commonly accepted sets of parameters indicate that heterozygote advantage could only account for the maintenance of four to five alleles. An analysis of previously published data suggest that local populations carry approximately ten alleles at both the K and D loci. These results indicate that either our estimates of the relevant parameters and number of alleles actually maintained contain significant errors, or that factors other than heterozygote advantage contribute to the maintenance of H-2 polymorphisms. We briefly review a number of mechanisms other than heterozygote advantage that could play a role in the maintenance of MHC polymorphisms, including frequency dependent selection, variation in pathogen assemblages across space and time, mating preferences, and transmission distortion. We present data from a retrospective analysis of backcross and F2 matings made during the early development of H-2 homozygous lines that show transmission distortion leading to a 52% deficiency of H-2 homozygotes (n=80, p<.002). This level of transmission distortion would contribute significantly to the maintenance of H-2 polymorphisms.


Major Histocompatibility Complex Frequency Dependent Selection Wild Mouse Major Histocompatibility Complex Allele Major Histocompatibility Complex Diversity 
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Copyright information

© Springer Science+Business Media New York 1987

Authors and Affiliations

  • Wayne K. Potts
    • 1
    • 2
  • C. Jo Manning
    • 3
  • Ammon B. Peck
    • 1
  • Marjorie Price-LaFace
    • 1
  • Edward K. Wakeland
    • 1
  1. 1.Laboratory of Molecular Biology, Department of PathologyUniversity of FloridaGainesvilleUSA
  2. 2.Department of ZoologyUniversity of WashingtonSeattleUSA
  3. 3.Department of PsychologyUniversity of WashingtonSeattleUSA

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