How pathogens drive genetic diversity: MHC, mechanisms and misunderstandings

Abstract

Major histocompatibility complex (MHC) genes have been put forward as a model for studying how genetic diversity is maintained in wild populations. Pathogen-mediated selection (PMS) is believed to generate the extraordinary levels of MHC diversity observed. However, establishing the relative importance of the three proposed mechanisms of PMS (heterozygote advantage, rare-allele advantage and fluctuating selection) has proved extremely difficult. Studies have attempted to differentiate between mechanisms of PMS using two approaches: (i) comparing MHC diversity with that expected under neutrality and (ii) relating MHC diversity to pathogen regime. Here, we show that in many cases the same predictions arise from the different mechanisms under these approaches, and that most studies that have inferred one mechanism of selection have not fully considered the alternative explanations. We argue that, while it may be possible to demonstrate that particular mechanisms of PMS are occurring, resolving their relative importance within a system is probably impossible. A more realistic target is to continue to demonstrate when and where the different mechanisms of PMS occur, with the aim of determining their relative importance across systems. We put forward what we believe to be the most promising approaches that will allow us to progress towards achieving this.

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

“…A functional hallmark of MHC genes is extensive diversification concentrated in the peptide-binding region (PBR). 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 influences infection with parasites and winter survival in the root vole Microtus oeconomus

“…They code membrane proteins that present antigens to T lymphocytes and thus are involved in mounting an immune response against pathogens. The MHC has been demonstrated to influence parasitic infections across a broad taxonomic range of non-model species in natural populations, and as such, it is believed that host-parasite interactions can drive high levels of polymorphism, which are characteristic of MHC loci (reviewed in Bernatchez and Landry 2003;Piertney and Oliver 2006;Spurgin and Richardson 2010). Three primary mechanisms explaining the role of parasites in maintaining MHC polymorphism have been proposed, although the determination of their relative importance remains an empirical challenge .…”

“…Although associations between MHC genes and infection with parasites are relatively well documented (reviewed in Spurgin and Richardson 2010), their fitness consequences are less well understood. Nevertheless, survival-related MHC alleles have been observed in the Seychelles warbler (Brouwer et al 2010), Soay sheep (Paterson et al 1998), and brushtail possum (Banks et al 2010).…”

Assembly and characterization of the MHC class I region of the Yangtze finless porpoise (Neophocaena asiaeorientalis asiaeorientalis)

“…Thus, it is usually difficult to isolate and identify independent MHC class I gene loci that respond to selection pressure, mate behavior, and parasite resistance using universal primers (Piertney and Oliver 2006;Spurgin and Richardson 2010).…”