MHC heterozygosity confers a selective advantage against multiple-strain infections

Penn, Dustin J.; Damjanovich, Kristy; Potts, Wayne K.

doi:10.1073/pnas.162006499

Cited by 557 publications

(491 citation statements)

References 52 publications

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“…(c) MHC and fitness Increased MHC diversity has been both theoretically and empirically linked to increased pathogen resistance and survival (Potts & Slev 1995;Hedrick 2002;Penn et al 2002). Indeed, strong pathogen-mediated balancing selection is thought to be responsible for maintaining the remarkably high levels of variation observed at several MHC loci in the otherwise genetically monomorphic endemic San Nicolas Island fox, Urocyon littoralis dickeyi (Aguilar et al 2004).…”

Section: Discussion (A) Mhc-based Mate Choicementioning

confidence: 99%

MHC-based patterns of social and extra-pair mate choice in the Seychelles warbler

et al. 2005

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The existence and nature of indirect genetic benefits to mate choice remain contentious. Major histocompatibility complex (MHC) genes, which play a vital role in determining pathogen resistance in vertebrates, may be the link between mate choice and the genetic inheritance of vigour in offspring. Studies have shown that MHC-dependent mate choice can occur in mammal and fish species, but little work has focused on the role of the MHC in birds. We tested for MHC-dependent mating patterns in the Seychelles warbler (Acrocephalus sechellensis). There was no influence of MHC class I exon 3 variation on the choice of social mate. However, females were more likely to obtain extra-pair paternity (EPP) when their social mate had low MHC diversity, and the MHC diversity of the extra-pair male was significantly higher than that of the cuckolded male. There was no evidence that females were mating disassortatively, or that they preferred males with an intermediate number of MHC bands. Overall, the results are consistent with the 'good genes' rather than the 'genetic compatibility' hypothesis. As female choice will result in offspring of higher MHC diversity, MHC-dependent EPP may provide indirect benefits in the Seychelles warbler if survival is positively linked to MHC diversity.

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Section: Discussion (A) Mhc-based Mate Choicementioning

confidence: 99%

MHC-based patterns of social and extra-pair mate choice in the Seychelles warbler

et al. 2005

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“…MHC heterozygosity has been shown to be associated with decreased infection rates in both laboratory and field studies (McClelland et al 2003;Froeschke and Sommer 2005), but several other studies have found no such association (Harf and Sommer 2005;Dionne et al 2009). Ilmonen et al (2007) found that wild-derived mice that were MHC heterozygotes did not show better resistance to Salmonella or better survival in semi-natural enclosures, even though earlier laboratory experiments documented a heterozygote advantage (Penn et al 2002). These results emphasise the importance of studies on wild, outbred species.…”

Section: Effects Of the Mhc On Infection And Survival Ratesmentioning

confidence: 95%

MHC influences infection with parasites and winter survival in the root vole Microtus oeconomus

et al. 2012

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Selective pressure from parasites is thought to maintain the polymorphism of major histocompatibility complex (MHC) genes. Although a number of studies have shown a relationship between the MHC and parasitic infections, the fitness consequences of such associations are less well documented. In the present paper, we characterised the variation in exon 2 of MHC class II DRB gene in the root vole and examined the effects of that gene on parasite prevalence and winter survival. We identified 18 unique exon 2 sequences, which translated into 10 unique amino acid sequences. Phylogenetic analysis revealed the presence of three distinct clusters, and allele distributions among these individuals suggested that the clusters correspond to three different loci. Although the rate of synonymous substitutions (d S ) exceeded the rate of nonsynonymous substitutions (d N ) across sequences, implying purifying selection, d N was significantly elevated at antigen-binding sites, suggesting that these sites could be under positive selection. Screening for parasites revealed a moderate prevalence of infection with gastrointestinal parasites (24 % infected), but a high infection rate for blood parasites (56 % infected). Infection with the blood parasite Babesia ssp. decreased survival almost twofold (25.7 vs. 13.9 %). Animals possessing the amino acid sequence AA*08 survived better than others (44.9 vs. 22 %), and they were infected with Babesia ssp. less often (13.9 vs 25.7 %). In contrast, individuals carrying allele AA*05 were infected more often (31.7 vs. 15.3 %). Heterozygosity at one of the putative loci was associated with a lower probability of infection with Babesia ssp., but at the other locus, the association was reversed. The unexpected latter result could be at least partly explained by the increased frequency of the susceptible allele AA*05 among heterozygotes. Overall, we demonstrate that infection with Babesia ssp. is a strong predictor of Electronic supplementary material The online version of this article

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“…A commonly held view is that the polymorphism is due to selection favoring MHC heterozygous hosts (Doherty and Zinkernagel 1975;Nei 1988, 1989;Takahata and Nei 1990;Hughes and Nei 1992). Since different MHC molecules bind different peptides, MHC heterozygous hosts can present a greater variety of peptides, and hence defend themselves against a larger variety of pathogens compared with MHC homozygous individuals (Penn et al 2002). It has indeed been shown that MHC heterozygosity correlates negatively with disease in HIV-infected patients (Carrington et al 1999), with HTLV-1 infection in humans (Jeffery et al 2000), and with LCMV infection in mice (Weidt et al 1995).…”

Section: Introductionmentioning

confidence: 99%

MHC polymorphism under host-pathogen coevolution

2004

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The genes encoding major histocompatibility (MHC) molecules are among the most polymorphic genes known for vertebrates. Since MHC molecules play an important role in the induction of immune responses, the evolution of MHC polymorphism is often explained in terms of increased protection of hosts against pathogens. Two selective pressures that are thought to be involved are (1) selection favoring MHC heterozygous hosts, and (2) selection for rare MHC alleles by host-pathogen coevolution. We have developed a computer simulation of coevolving hosts and pathogens to study the relative impact of these two mechanisms on the evolution of MHC polymorphism. We found that heterozygote advantage per se is insufficient to explain the high degree of polymorphism at the MHC, even in very large host populations. Host-pathogen coevolution, on the other hand, can easily account for realistic polymorphisms of more than 50 alleles per MHC locus. Since evolving pathogens mainly evade presentation by the most common MHC alleles in the host population, they provide a selective pressure for a large variety of rare MHC alleles. Provided that the host population is sufficiently large, a large set of MHC alleles can persist over many host generations under hostpathogen coevolution, despite the fact that allele frequencies continuously change.

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MHC heterozygosity confers a selective advantage against multiple-strain infections

Cited by 557 publications

References 52 publications

MHC-based patterns of social and extra-pair mate choice in the Seychelles warbler

MHC-based patterns of social and extra-pair mate choice in the Seychelles warbler

MHC influences infection with parasites and winter survival in the root vole Microtus oeconomus

MHC polymorphism under host-pathogen coevolution

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