Heterozygote advantage fails to explain the high degree of polymorphism of the MHC View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2004-01-13

AUTHORS

Rob J. De Boer, José A. M. Borghans, Michiel van Boven, Can Keşmir, Franz J. Weissing

ABSTRACT

Major histocompatibility (MHC) molecules are encoded by extremely polymorphic genes and play a crucial role in vertebrate immunity. Natural selection favors MHC heterozygous hosts because individuals heterozygous at the MHC can present a larger diversity of peptides from infectious pathogens than homozygous individuals. Whether or not heterozygote advantage is sufficient to account for a high degree of polymorphism is controversial, however. Using mathematical models we studied the degree of MHC polymorphism arising when heterozygote advantage is the only selection pressure. We argue that existing models are misleading in that the fitness of heterozygotes is not related to the MHC alleles they harbor. To correct for this, we have developed novel models in which the genotypic fitness of a host directly reflects the fitness contributions of its MHC alleles. The mathematical analysis suggests that a high degree of polymorphism can only be accounted for if the different MHC alleles confer unrealistically similar fitnesses. This conclusion was confirmed by stochastic simulations, including mutation, genetic drift, and a finite population size. Heterozygote advantage on its own is insufficient to explain the high population diversity of the MHC. More... »

PAGES

725-731

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00251-003-0629-y

DOI

http://dx.doi.org/10.1007/s00251-003-0629-y

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1016761071

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/14722686


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