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Dryad

Heterozygote advantage can explain the extraordinary diversity of immune genes

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Nov 25, 2024 version files 72.88 KB

Abstract

The majority of highly polymorphic genes are related to immune functions and with over 100 alleles within a population, genes of the major histocompatibility complex (MHC) are the most polymorphic loci in vertebrates. How such extraordinary polymorphism arose and is maintained is controversial. One possibility is heterozygote advantage (HA), which can in principle maintain any number of alleles, but biologically explicit models based on this mechanism have so far failed to reliably predict the coexistence of significantly more than ten alleles. We here present an eco-evolutionary model showing that under HA evolution can result in the emergence and maintenance of more than 100 alleles if the following two assumptions are fulfilled: first, pathogens are lethal in the absence of an appropriate immune defense; second, the combined effect of multiple pathogens on host survival exceeds the sum of the effects of each pathogen alone. Thus, our results show that HA can be a more potent force in explaining the extraordinary polymorphism found at MHC loci than currently recognized.