The Nature of Selection on the Major Histocompatibility Complex

Critical Reviews in Immunology
V ApaniusWayne K Potts

Abstract

Only natural selection can account for the extreme genetic diversity of genes of the major histocompatibility complex (MHC). Although the structure and function of classic MHC genes is well understood at the molecular and cellular levels, there is controversy about how MHC diversity is selectively maintained. The diversifying selection can be driven by pathogen interactions and inbreeding avoidance mechanisms. Pathogen-driven selection can maintain MHC polymorphism based on heterozygote advantage or frequency-dependent selection due to pathogen evasion of MHC-dependent immune recognition. Empirical evidence demonstrates that specific MHC haplotypes are resistant to certain infectious agents, while susceptible to others. These data are consistent with both heterozygote advantage and frequency-dependent models. Additional research is needed to discriminate between these mechanisms. Infectious agents can precipitate autoimmunity and can potentially contribute to MHC diversity through molecular mimicry and by favoring immunodominance. MHC-dependent abortion and mate choice, based on olfaction, can also maintain MHC diversity and probably functions both to avoid genome-wide inbreeding and produce MHC-heterozygous offspring with incr...Continue Reading

Citations

Nov 21, 2018·Virologica Sinica·Jiajie Wei, Jonathan W Yewdell
Apr 21, 2020·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Jan HavlíčekS Craig Roberts
Aug 30, 2020·Nature Reviews. Genetics·Dieter Ebert, Peter D Fields
Aug 3, 2021·Frontiers in Cell and Developmental Biology·Xinwen WangXiaochun Bai
Aug 6, 2021·Scientific Reports·Jaakko L O PohjoismäkiSteve Smith

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