Advances in the evolutionary understanding of MHC polymorphism

J Radwan, Wiesław Babik, Jim Kaufman, Tobias L. Lenz, Jamie Winternitz

Research output: Contribution to journalArticlepeer-review


Proteins encoded by the classical major histocompatibility complex (MHC) genes incite the vertebrate adaptive immune response by presenting peptide antigens on the cell surface.

Here, we review mechanisms explaining landmark features of these genes: extreme polymorphism, excess of non-synonymous changes in peptide-binding domains and long gene genealogies. Recent studies provide evidence that these features may arise due to pathogens evolving ways to evade immune response guided by the locally common MHC alleles. However, complexities of selection on MHC genes are simultaneously being revealed that need to be incorporated into existing theory. These include pathogen-driven selection for antigen binding breadth and expansion of the MHC gene family, associated autoimmunity trade-offs, hitchhiking of deleterious mutations linked to the MHC, geographic subdivision and adaptive introgression.
Original languageEnglish
Pages (from-to)298-311
JournalTrends in Genetics
Issue number4
Early online date7 Feb 2020
Publication statusE-pub ahead of print - 7 Feb 2020


  • balancing selection
  • major histocompatibility complex
  • polymorphism
  • negative 16 frequency-dependent selection
  • heterozygote advantage
  • MHC-KIR interaction


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