Disentangling the roles of natural selection and genetic drift in shaping variation at MHC immunity genes

Abstract

The major histocompatibility complex (MHC) forms an integral component of the vertebrate immune response and, due to strong selection pressures, is one of the most polymorphic regions of the entire genome. Despite over 15 years of research, empirical studies offer highly contradictory explanations of the relative roles of different evolutionary forces, selection and genetic drift, acting on MHC genes during population bottlenecks. Here, we take a meta-analytical approach to quantify the results of studies into the effects of bottlenecks on MHC polymorphism. We show that the consequences of selection acting on MHC loci prior to a bottleneck event, combined with drift during the bottleneck, will result in overall loss of MHC polymorphism that is ∼15% greater than loss of neutral genetic diversity. These results are counter to general expectations that selection should maintain MHC polymorphism, but do agree with the results of recent simulation models and at least two empirical studies. Notably, our results suggest that negative frequency-dependent selection could be more important than overdominance for maintaining high MHC polymorphism in pre-bottlenecked populations.

Extensive diversification of MHC in Chinese giant salamanders Andrias davidianus (Anda-MHC) reveals novel splice variants

“…MHC diversity is tightly linked to diseases resistance, and maintained through balancing selection mediated by hostpathogen co-evolution (Piertney and Oliver, 2006;Spurgin and Richardson, 2010). Hence, the well-characterized function of MHC in immune defense, alongside their outstanding diverse nature, makes them exceptional candidates to study patterns of adaptive genetic variation determining pathogen resistance, specially in species of conservation concern (Sutton et al, 2011).…”

MHC class II diversity of koala (Phascolarctos cinereus) populations across their range

“…The limited population structure at MHC loci in these populations supports that, between populations within regions, the selective pressures or loss of diversity are similar. The degree of loss in MHC diversity can be greater than that of neutral diversity, because of the uneven MHC allele distribution caused by negative dependent selection (Sutton et al, 2011). This could be applicable to koalas in the north, whereby the few population-unique variants are a possible result of the differential loss of rare variants between populations following habitat decline and genetic drift.…”

Sexual selection and the evolutionary dynamics of the major histocompatibility complex

“…By stabilizing allele frequency variation at equilibrium, disassortative mating creates the optimal conditions for the maintenance of functional genetic variation in small populations [40]. Empirical studies indicate that MHC variation is often eroded during population bottlenecks at a rate that equals or exceeds that of neutral loci [29,41], but exceptional cases have been documented in which MHC variation has been maintained in the face of severe declines in population size [42,43]. Analyses of the intensity of sexual selection in such populations could help to explain whether non-random mating during periods of population decline and recovery can contribute to the maintenance of MHC diversity.…”

“…Unfortunately, while both natural and sexual selection probably contribute to the generation and maintenance of MHC diversity, the two mechanisms are expected to generate qualitatively similar patterns of variation, enhancing both allelic diversity and heterozygosity, something which has complicated efforts to discriminate their relative importance in wild populations [11,29]. Previous efforts to model the effects of selection on patterns of MHC variation have investigated the effects of natural and sexual selection in isolation, and have been unable to address the key question of how these two forms of selection are likely to interact in natural systems [30][31][32][33].…”