Heterozygote advantage can explain the extraordinary diversity of immune genes

Abstract

AbstractThe 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 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 present an eco-evolutionary model showing that evolution can in a self-organising process result in the emergence of more than 100 alleles maintained by heterozygote advantage. Thus, our model shows that heterozygote advantage is a much more potent force in explaining the extraordinary polymorphism found at MHC loci than currently recognised. Our model applies more generally and can explain polymorphism at any gene involved in multiple functions important for survival.