Evolution of major histocompatibility complex gene copy number

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.

Long-Read Genome Assemblies Reveal Extraordinary Variation in the Number and Structure of MHC Loci in Birds

“…Some superfamilies (especially Sylvioidea, Passeroidea, and Muscicapoidea) with dozens of MHC loci, would seem to require a magnitude higher number of pathogens than basal groups, which does not appear biologically feasible ( Bentkowski and Radwan 2019 ). Another possibility is that there are different intrinsic costs of expressing many MHC variants between passerines and nonpasserines ( Bentkowski and Radwan 2019 ). For example, there could be different tradeoffs between MHC and T cell receptor diversity for these groups ( Migalska et al.…”

“…Sexual selection, maternal–fetal interactions, and demographic processes, such as genetic drift can also affect the evolution of the MHC and, hence, the number of loci ( Piertney and Oliver 2006 ). More recently, computer simulations suggest that complex interactions between three factors (pathogen richness, the intrinsic cost of expressing additional MHC variants, and pathogen mutation rate) drives the number of MHC genes in the genome ( Bentkowski and Radwan 2019 ). These interactions can generate variation in the number of MHC loci within species (paralogs) as well as between species (orthologs).…”

Endless forms of sexual selection

“…In one of these species with high extrapair mating, the bluethroat Luscinia svecica, individuals can have up to 56 different alleles and thus a minimum of 28 duplicated loci (Rekdal et al, 2018). Gene duplications ensure a high within-individual allelic repertoire and can be favoured under high pathogen pressure (Bentkowski & Radwan, 2019; Minias et al, 2018). Mate choice for resistant mates or mates that enhances the pathogen resistance in offspring will reinforce the natural selection for gene duplications.…”

Trade‐offs in expressed major histocompatibility complex diversity seen on a macroevolutionary scale among songbirds

“…2009; Eizaguirre et al. 2011; Bentkowski and Radwan 2019). Differences in optimal MHC diversity may help to explain the large between‐species variation and lower within‐species variation in MHC gene copy number in genomic DNA seen across many songbird species (O'Connor et al.…”