Abstract
MHC genes, which code for proteins responsible for presenting pathogen-derived antigens to the host immune system, show remarkable copy-number variation both between and within species. However, the evolutionary forces driving this variation are poorly understood. Here, we use computer simulations to investigate whether evolution of the number of MHC variants in the genome can be shaped by the number of pathogen species the host population encounters (pathogen richness). Our model assumed that while increasing a range of pathogens recognised, expressing additional MHC variants also incurs costs such as an increased risk of autoimmunity. We found that pathogen richness selected for high MHC copy number only when the costs were low. Furthermore, the shape of the association was modified by the rate of pathogen evolution, with faster pathogen mutation rates selecting for increased host MHC copy number, but only when pathogen richness was low to moderate. Thus, taking into account factors other than pathogen richness may help explain wide variation between vertebrate species in the number of MHC genes. Within population, variation in the number of unique MHC variants carried by individuals (INV) was observed under most parameter combinations, except at low pathogen richness. This variance gave rise to positive correlations between INV and host immunocompetence (proportion of pathogens recognised). However, within-population variation in host immunocompetence declined with pathogen richness. Thus, counterintuitively, pathogens can contribute more to genetic variance for host fitness in species exposed to fewer pathogen species, with consequences to predictions from “Hamilton-Zuk” theory of sexual selection.
Highlights
Major histocompatibility complex (MHC) genes code for proteins that present pathogenderived oligopeptides to T-cells, initiating an adaptive immune response
The polymorphism is driven by coevolution with parasites which are selected to evade recognition by MHC proteins
Expressing many MHC molecules could ensure that an individual could present antigens of most pathogen species encountered, but this comes at a cost, such as enhanced negative selection on lymphocytes leading to holes in T-cell receptor repertoire
Summary
Major histocompatibility complex (MHC) genes code for proteins that present pathogenderived oligopeptides (antigens) to T-cells, initiating an adaptive immune response. MHC genes are highly polymorphic, with dozens to hundreds of variants typically segregating in natural populations (reviewed in [1,2,3]) This extreme polymorphism is thought to result from balancing selection imposed by pathogenic organisms [4, 5], and broadly-reported associations between MHC variants and susceptibility to infection are consistent with the role of pathogens in driving MHC evolution (reviewed in [3]). A meta-analysis based on 112 mammalian species showed that the signs, let alone the strength, of such associations may vary between taxa [10] Interpretation of these differences is hindered by the scarcity of theoretical work exploring the impact of parasite richness on MHC diversity
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