Number Of Major Histocompatibility Complex Alleles Research Articles

Relationship between genome-wide and MHC class I and II genetic diversity and complementarity in a nonhuman primate.

Although mate choice is expected to favor partners with advantageous genetic properties, the relative importance of genome‐wide characteristics, such as overall heterozygosity or kinship, versus specific loci, is unknown. To disentangle genome‐wide and locus‐specific targets of mate choice, we must first understand congruence in global and local variation within the same individual. This study compares genetic diversity, both absolute and relative to other individuals (i.e., complementarity), assessed across the genome to that found at the major histocompatibility complex (MHC), a hyper‐variable gene family integral to immune system function and implicated in mate choice across species. Using DNA from 22 captive olive baboons (Papio anubis), we conducted double digest restriction site‐associated DNA sequencing to estimate genome‐wide heterozygosity and kinship, and sequenced two class I and two class II MHC loci. We found that genome‐wide diversity was not associated with MHC diversity, and that diversity at class I MHC loci was not correlated with diversity at class II loci. Additionally, kinship was a significant predictor of the number of MHC alleles shared between dyads at class II loci. Our results provide further evidence of the strong selective pressures maintaining genetic diversity at the MHC in comparison to other randomly selected sites throughout the genome. Furthermore, our results indicate that class II MHC disassortative mate choice may mediate inbreeding avoidance in this population. Our study suggests that mate choice favoring genome‐wide genetic diversity is not always synonymous with mate choice favoring MHC diversity, and highlights the importance of controlling for kinship when investigating MHC‐associated mate choice.

Evolution of innate and adaptive immune genes in a non-model waterbird, the common tern.

Toll-like receptors (TLRs) and the Major Histocompatibility Complex (MHC) are the key pathogen-recognition genes of vertebrate immune system and they have a crucial role in the initiation of innate and adaptive immune response, respectively. Recent advancements in sequencing technology sparked research on highly duplicated MHC genes in non-model species, but TLR variation in natural vertebrate populations has remained little studied and comparisons of polymorphism across both TLRs and MHC are scarce. Here, we aimed to compare variation across innate (four TLR loci) and adaptive (MHC class I and class II) immune genes in a non-model avian species, the common tern Sterna hirundo. We detected relatively high allelic richness at TLR genes (9-48 alleles per locus), which was similar to or even higher than the estimated per locus allelic richness at the MHC (24-30 alleles at class I and 13-16 alleles at class II under uniform sample sizes). Despite this, the total number of MHC alleles across all duplicated loci (four class I and three class II) was much higher and MHC alleles showed greater sequence divergence than TLRs. Positive selection targeted relatively more sites at the MHC than TLRs, but the strength of selection (dN/dS ratios) at TLRs was higher when compared to MHC class I. There were also differences in the signature of positive selection and recombination (gene conversion) between MHC class I and II (stronger signature at class II), suggesting that mechanisms maintaining variation at the MHC may vary between both classes. Our study indicates that allelic richness of both innate and adaptive immune receptors may be maintained at relatively high levels in viable avian populations and we recommend a transition from the traditional gene-specific to multi-gene approach in studying molecular evolution of vertebrate immune system.

Urbanization processes drive divergence at the major histocompatibility complex in a common waterbird.

Urban sprawl is one of the most common landscape alterations occurring worldwide, and there is a growing list of species that are recognised to have adapted to urban life. To be successful, processes of urban colonization by wildlife require a broad spectrum of phenotypic (e.g., behavioural or physiological) adjustments, but evidence for genetic adaptations is much scarcer. One hypothesis proposes that different pathogen-driven selective pressures between urban and non-urban landscapes leads to adaptations in host immune genes. Here, we examined urbanization-related differentiation at the key pathogen-recognition genes of vertebrate adaptive immunity-the major histocompatibility complex (MHC)-in a common waterbird, the Eurasian coot (Fulica atra). Samples were collected from an old urban population (established before the 1950s), a new urban population (established in the 2000s), and two rural populations from central Poland. We found strong significant divergence (as measured with Jost’s D) at the MHC class II between the old urban population and the remaining (new urban and rural) populations. Also, there was a moderate, but significant divergence at the MHC between the new urban population and two rural populations, while no divergence was found between the two rural populations. The total number of MHC alleles and the number of private (population-specific) MHC alleles was lower in old urban populations, as compared to the rural ones. These patterns of differentiation at the MHC were not consistent with patterns found for neutral genetic markers (microsatellites), which showed few differences between the populations. Our results indicate that MHC allele composition depended on the level of anthropogenic disturbance and the time which passed since urban colonization, possibly due to the processes of genotype sorting and local adaptation. As such, our study contributes to the understanding of genetic mechanisms associated with urbanization processes in wildlife.

Mating preferences can drive expansion or contraction of major histocompatibility complex gene family.

Major histocompatibility complex (MHC)-based mating rules can evolve as a way to avoid inbreeding or to increase offspring immune competence. While the role of mating preference in shaping the MHC diversity in vertebrates has been acknowledged, its impact on individual MHC diversity has not been considered. Here, we use computer simulations to investigate how simple mating rules favouring MHC-dissimilar partners affect the evolution of the number of MHC variants in individual genomes, accompanying selection for resistance to parasites. We showed that the effect of such preferences could sometimes be dramatic. If preferences are aimed at avoiding identical alleles, the equilibrium number of MHC alleles is much smaller than under random mating. However, if the mating rule minimizes the ratio of shared to different alleles in partners, MHC number is higher than under random mating. Additionally, our simulations revealed that a negative correlation between the numbers of MHC variants in mated individuals can arise from simple rules of MHC-disassortative mating. Our results reveal unexpected potential of MHC-based mating preferences to drive MHC gene family expansions or contractions and highlight the need to study the mechanistic basis of such preferences, which is currently poorly understood.

Immunological MHC supertypes and allelic expression: how low is the functional MHC diversity in free-ranging Namibian cheetahs?

Cheetahs (Acinonyx jubatus) are a textbook example of how habitat loss, human-wildlife conflicts and historic bottlenecks depleted genetic variability, both genome-wide and at the major histocompatibility complex (MHC), which plays an integral role in the adaptive immune response. However, free-ranging Namibian cheetahs show no signs of impaired immunocompetence or health. This contradicts theoretical expectations and poses the question whether the manner by which MHC diversity is judged needs to be revised. Here, we show that free-ranging Namibian cheetahs still harbour MHC alleles that are divergent enough to cover several functionally distinct MHC supertypes and thus are probably capable of binding and presenting a relatively broad range of antigens to T-cells. We detected a similar pattern in three other free-ranging, strongly bottlenecked cat species, supporting the hypothesis that species with a low MHC allelic diversity might be able to retain functional diversity not within but across loci. Moreover, the allelic composition influences the level of MHC class I and class II expression which also might play a significant role in pathogen defence. Thus, our study indicates that the evolutionary role of MHC diversity goes beyond counting the remaining number of MHC alleles and offers an explanation as to how cat species might have avoided impaired immuno-competence, despite showing low MHC allelic diversity. Although the low MHC diversity currently seems to be sufficient to ensure the health of free-ranging cheetahs, it is currently unknown whether it can provide sufficient protection from future threats through emerging new pathogens.

Female assortative mate choice functionally validates synthesized male odours of evolving stickleback river-lake ecotypes.

During mate choice decisions, females of many vertebrates use male olfactory cues to achieve immunogenetic optimality of their offspring. Three-spined sticklebacks (Gasterosteus aculeatus) populating habitats that differ in their parasite communities evolve locally adapted combinations of genetic variants encoded at the major histocompatibility complex (MHC). Such adaptation confers optimal resistance to the local parasite fauna. Immunogenetic signatures co-evolved with local parasites favour population-specific assortative mate choice behaviour. Previous studies have shown that female sticklebacks evaluate male MHC-associated olfactory cues during the process of mate choice, but how habitat-specific information is exchanged between males and females has remained elusive. Here, we directly demonstrate the molecular nature of the olfactory cue providing habitat-specific information. Under controlled laboratory conditions, females that are ready to mate prefer mixtures of synthetic MHC peptide ligands mimicking the optimal allele number of their original population. These results imply that female sticklebacks can determine the number of MHC alleles of their prospective mates, compare it to their own immunogenetic status, and, if optimal with respect to the immunogenetic complementarity, accept the male as mate. Our results suggest a potentially common mechanism of ecological speciation in vertebrates that is based on the olfactory assessment of habitat-specific immunogenetic diversity.

MHC-correlated preferences in diestrous female horses (Equus caballus)

Genes of the major histocompatibility complex (MHC) have been shown to influence communication in many vertebrates, possibly with context-specific MHC-correlated reactions. Here we test for MHC-linked female preferences in the polygynous horse (Equus caballus) by repeatedly exposing 19 mares to a group of seven sexually experienced stallions. Each mare was tested four times during two consecutive reproductive cycles, twice during estrus and twice during diestrus. Male plasma testosterone concentrations were determined from weekly blood samples, and equine leukocyte antigen (ELA) class I and II alleles were determined serologically at the end of the experiments. Perception of male attractiveness was strongly dependent on estrous cycle: mean preference scores did not correlate for mares in diestrus and estrus and varied more during estrus than during diestrus. We found elevated female interests for MHC-dissimilar stallions, but only during diestrus, not during estrus. Female preferences were not significantly predicted by mean male testosterone plasma concentrations. However, testosterone concentrations changed during the 11 weeks of the experiment. By the end of the experiment, average testosterone concentration was significantly correlated to the average number of MHC alleles the stallions shared with the mares. We conclude that the MHC affects female preferences for stallions, but non-MHC linked male characteristics can overshadow effects of the MHC during estrus.

Lack of Spatial Immunogenetic Structure among Wolverine (Gulo gulo) Populations Suggestive of Broad Scale Balancing Selection.

Elucidating the adaptive genetic potential of wildlife populations to environmental selective pressures is fundamental for species conservation. Genes of the major histocompatibility complex (MHC) are highly polymorphic, and play a key role in the adaptive immune response against pathogens. MHC polymorphism has been linked to balancing selection or heterogeneous selection promoting local adaptation. However, spatial patterns of MHC polymorphism are also influenced by gene flow and drift. Wolverines are highly vagile, inhabiting varied ecoregions that include boreal forest, taiga, tundra, and high alpine ecosystems. Here, we investigated the immunogenetic variation of wolverines in Canada as a surrogate for identifying local adaptation by contrasting the genetic structure at MHC relative to the structure at 11 neutral microsatellites to account for gene flow and drift. Evidence of historical positive selection was detected at MHC using maximum likelihood codon-based methods. Bayesian and multivariate cluster analyses revealed weaker population genetic differentiation at MHC relative to the increasing microsatellite genetic structure towards the eastern wolverine distribution. Mantel correlations of MHC against geographical distances showed no pattern of isolation by distance (IBD: r = -0.03, p = 0.9), whereas for microsatellites we found a relatively strong and significant IBD (r = 0.54, p = 0.01). Moreover, we found a significant correlation between microsatellite allelic richness and the mean number of MHC alleles, but we did not observe low MHC diversity in small populations. Overall these results suggest that MHC polymorphism has been influenced primarily by balancing selection and to a lesser extent by neutral processes such as genetic drift, with no clear evidence for local adaptation. This study contributes to our understanding of how vulnerable populations of wolverines may respond to selective pressures across their range.

Positive selection drives the evolution of a major histocompatibility complex gene in an endangered Mexican salamander species complex.

Immune gene evolution can be critical to species survival in the face of infectious disease. In particular, polymorphism in the genes of the major histocompatibility complex (MHC) helps vertebrates combat novel and diverse pathogens by increasing the number of pathogen-derived proteins that can initiate the host's acquired immune response. In this study, we used a combination of presumably adaptive and neutral markers to investigate MHC evolution in populations of five salamander species within the Ambystoma velasci complex, a group consisting of 15 recently diverged species, several of which are endangered. We isolated 31 unique MHC class II β alleles from 75 total individuals from five species in this complex. MHC heterozygosity was significantly lower than expected for all five species, and we found no clear relationship between number of MHC alleles and species range, life history, or level of heterozygosity. We inferred a phylogeny representing the evolutionary history of Ambystoma MHC, with which we found signatures of positive selection on the overall gene, putative peptide-binding residues, and allelic lineages. We identified several instances of trans-species polymorphism, a hallmark of balancing selection observed in other groups of closely related species. In contrast, we did not detect comparable allelic diversity or signatures of selection on neutral loci. Additionally, we identified 17 supertypes among the 44 unique Ambystoma alleles, indicating that these sequences may encode functionally distinct MHC variants. We therefore have strong evidence that positive selection is a major evolutionary force driving patterns of MHC polymorphism in this recently radiated species complex.

No evidence for the effect of MHC on male mating success in the brown bear.

Mate choice is thought to contribute to the maintenance of the spectacularly high polymorphism of the Major Histocompatibility Complex (MHC) genes, along with balancing selection from parasites, but the relative contribution of the former mechanism is debated. Here, we investigated the association between male MHC genotype and mating success in the brown bear. We analysed fragments of sequences coding for the peptide-binding region of the highly polymorphic MHC class I and class II DRB genes, while controlling for genome-wide effects using a panel of 18 microsatellite markers. Male mating success did not depend on the number of alleles shared with the female or amino-acid distance between potential mates at either locus. Furthermore, we found no indication of female mating preferences for MHC similarity being contingent on the number of alleles the females carried. Finally, we found no significant association between the number of MHC alleles a male carried and his mating success. Thus, our results provided no support for the role of mate choice in shaping MHC polymorphism in the brown bear.

Parasite load and MHC diversity in undisturbed and agriculturally modified habitats of the ornate dragon lizard.

Major histocompatibility complex (MHC) gene polymorphism is thought to be driven by host-parasite co-evolution, but the evidence for an association between the selective pressure from parasites and the number of MHC alleles segregating in a population is scarce and inconsistent. Here, we characterized MHC class I polymorphism in a lizard whose habitat preferences (rock outcrops) lead to the formation of well-defined and stable populations. We investigated the association between the load of ticks, which were used as a proxy for the load of pathogens they transmit, and MHC class I polymorphism across populations in two types of habitat: undisturbed reserves and agricultural land. We hypothesized that the association would be positive across undisturbed reserve populations, but across fragmented agricultural land populations, the relationship would be distorted by the loss of MHC variation due to drift. After controlling for habitat, MHC diversity was not associated with tick number, and the habitats did not differ in this respect. Neither did we detect a difference between habitats in the relationship between MHC and neutral diversity, which was positive across all populations. However, there was extensive variation in the number of MHC alleles per individual, and we found that tick number was positively associated with the average number of alleles carried by lizards across reserve populations, but not across populations from disturbed agricultural land. Our results thus indicate that local differences in selection from parasites may contribute to MHC copy number variation within species, but habitat degradation can distort this relationship.

Pathogen burden, co-infection and major histocompatibility complex variability in the European badger (Meles meles).

Pathogen-mediated selection is thought to maintain the extreme diversity in the major histocompatibility complex (MHC) genes, operating through the heterozygote advantage, rare-allele advantage and fluctuating selection mechanisms. Heterozygote advantage (i.e. recognizing and binding a wider range of antigens than homozygotes) is expected to be more detectable when multiple pathogens are considered simultaneously. Here, we test whether MHC diversity in a wild population of European badgers (Meles meles) is driven by pathogen-mediated selection. We examined individual prevalence (infected or not), infection intensity and co-infection of 13 pathogens from a range of taxa and examined their relationships with MHC class I and class II variability. This population has a variable, but relatively low, number of MHC alleles and is infected by a variety of naturally occurring pathogens, making it very suitable for the investigation of MHC-pathogen relationships. We found associations between pathogen infections and specific MHC haplotypes and alleles. Co-infection status was not correlated with MHC heterozygosity, but there was evidence of heterozygote advantage against individual pathogen infections. This suggests that rare-allele advantages and/or fluctuating selection, and heterozygote advantage are probably the selective forces shaping MHC diversity in this species. We show stronger evidence for MHC associations with infection intensity than for prevalence and conclude that examining both pathogen prevalence and infection intensity is important. Moreover, examination of a large number and diversity of pathogens, and both MHC class I and II genes (which have different functions), provide an improved understanding of the mechanisms driving MHC diversity.

Intermediate number of major histocompatibility complex class IIB length variants relates to enlarged perivisceral fat deposits in the blunt-head cichlid Tropheus moorii.

Studying the genetic basis of host-parasite interactions represents an outstanding opportunity to observe eco-evolutionary processes. Established candidates for such studies in vertebrates are immunogenes of the major histocompatibility complex (MHC). The MHC has been reported to reach high intra- and interindividual diversity, and a diverse MHC might be advantageous when facing infections from multiple parasites. However, other studies indicated that individuals with an intermediate number of MHC alleles are less infected with parasites or have other fitness advantages. In this study, we assessed the optimal number of MHC alleles in the blunt-head cichlid Tropheus moorii from Lake Tanganyika. We investigated the influence of the interindividual variation in number of MHC length variants on parasite infection and body condition, measured by the amount of perivisceral fat reserves. Surprisingly, there was no correlation between parasite infection and number of MHC length variants or perivisceral fat deposits. However, the individual number of MHC length variants significantly correlated with the amount of perivisceral fat deposits in males, suggesting that male individuals with an intermediate number of alleles might be able to use their fat reserves more efficiently.

Variation in positively selected major histocompatibility complex class I loci in rufous-collared sparrows (Zonotrichia capensis).

The major histocompatibility complex (MHC) is a highly variable family of genes involved in parasite recognition and the initiation of adaptive immune system responses. Variation in MHC loci is maintained primarily through parasite-mediated selection or disassortative mate choice. To characterize MHC diversity of rufous-collared sparrows (Zonotrichia capensis), an abundant South American passerine, we examined allelic and nucleotide variation in MHC class I exon 3 using pyrosequencing. Exon 3 comprises a substantial portion of the peptide-binding region (PBR) of class I MHC and thus plays an important role in intracellular pathogen defense. We identified 98 putatively functional alleles that produce 56 unique protein sequences across at least 6 paralogous loci. Allelic diversity per individual and exon-wide nucleotide diversity were relatively low; however, we found specific amino acid positions with high nucleotide diversity and signatures of positive selection (elevated d N /d S ) that may correspond to the PBR. Based on the variation in physicochemical properties of amino acids at these "positively selected sites," we identified ten functional MHC supertypes. Spatial variation in nucleotide diversity and the number of MHC alleles, proteins, and supertypes per individual suggests that environmental heterogeneity may affect patterns of MHC diversity. Furthermore, populations with high MHC diversity have higher prevalence of avian malaria, consistent with parasite-mediated selection on MHC. Together, these results provide a framework for subsequent investigations of selective agents acting on MHC in Z. capensis.

Global distribution of malaria-resistant MHC-HLA alleles: the number and frequencies of alleles and malaria risk.

BackgroundThe major histocompatibility complex (MHC) is the most polymorphic genetic region in vertebrates, but the origin of such genetic diversity remains unresolved. Several studies have demonstrated at the within-population level that individuals harbouring particular alleles can be less or more susceptible to malaria, but these do not allow strong generalization.MethodsHere worldwide data on the frequencies of several hundred MHC alleles of the human leucocyte antigen (HLA) system in relation to malaria risk at the between-population level were analysed in a phylogenetic framework, and results for different alleles were quantitatively summarized in a meta-analysis.ResultsThere was an overall positive relationship between malaria pressure and the frequency of several HLA alleles indicating that allele frequencies increase in countries with strong malaria pressure. Nevertheless, considerable heterogeneity was observed across alleles, and some alleles showed a remarkable negative relationship with malaria risk. When heterogeneities were partitioned into different organization groups of the MHC, the strongest positive relationships were detected for alleles of the HLA-A and HLA-B loci, but there were also differences between MHC supertypes that constitute functionally distinct nucleotide sequences. Finally, the number of MHC alleles that are maintained within countries was also related to malaria risk.ConclusionTherefore, malaria represents a key selection pressure for the human MHC and has left clear evolutionary footprints on both the frequencies and the number of alleles observed in different countries.Electronic supplementary materialThe online version of this article (doi:10.1186/1475-2875-13-349) contains supplementary material, which is available to authorized users.

Loss of Genetic Diversity at an MHC Locus in the Endangered Tokyo BitterlingTanakia tanago(Teleostei: Cyprinidae)

Genetic diversity at a major histocompatibility complex (MHC) class II B gene was examined for two wild and three captive populations of the endangered Tokyo bitterling Tanakia tanago. A specific primer set was first developed to amplify the MHC II B exon 2 locus. Using single strand conformation polymorphism (SSCP) and sequencing analysis, 16 DAB3 alleles were detected with 56 nucleotide substitutions in the 276-bp region. In the putative antigen-binding sites of exon 2, the rate of nonsynonymous substitutions was significantly higher than that of synonymous substitutions (dN/dS = 2.79), indicating positive selection on the retention of polymorphism. The population from the Handa Natural Habitat Conservation Area and that from the Tone River system exhibited low variation (one and three alleles, respectively), whereas the captive population that originated from a mix of three distinct populations had the highest amounts of variation (14 alleles). The levels of heterozygosity at the MHC varied considerably among populations and showed significant correlations with those at putative neutral microsatellite markers, suggesting that genetic drift following a bottleneck has affected MHC variability in some populations. Comparisons between endangered and non-endangered fish species in previous reports and the present results indicate that the number of MHC alleles per population is on average 70% lower in endangered species than non-endangered species. Considering the functional consequence of this locus, attention should be paid to captive and wild endangered fish populations in terms of further loss of MHC alleles.

Female house sparrows "count on" male genes: experimental evidence for MHC-dependent mate preference in birds

BackgroundFemales can potentially assess the quality of potential mates using their secondary sexual traits, and obtain "good genes" that increase offspring fitness. Another potential indirect benefit from mating preferences is genetic compatibility, which does not require extravagant or viability indicator traits. Several studies with mammals and fish indicate that the genes of the major histocompatibility complex (MHC) influence olfactory cues and mating preferences, and such preferences confer genetic benefits to offspring. We investigated whether individual MHC diversity (class I) influences mating preferences in house sparrows (Passer domesticus).ResultsOverall, we found no evidence that females preferred males with high individual MHC diversity. Yet, when we considered individual MHC allelic diversity of the females, we found that females with a low number of alleles were most attracted to males carrying a high number of MHC alleles, which might reflect a mating-up preference by allele counting.ConclusionsThis is the first experimental evidence for MHC-dependent mating preferences in an avian species to our knowledge. Our findings raise questions about the underlying mechanisms through which birds discriminate individual MHC diversity among conspecifics, and they suggest a novel mechanism through which mating preferences might promote the evolution of MHC polymorphisms and generate positive selection for duplicated MHC loci.

CTLs' repertoire shaping in the thymus: A Monte Carlo simulation

Motivation: The human immune system evolved a multi-layered control mechanism to eliminate self-reactive cells. Of these so-called tolerance induction mechanisms, lymphocytes T education in the thymus gland represents the very first one. This complicated process is not fully understood and quantitative models able to help in this endeavor are lacking. Here, we present a stochastic computational model of the thymus which combines data-driven prediction methods and a novel method based on protein–protein potential measurements for assessing molecular binding among cell receptors, major histocompatibility complex (MHC) molecules, and self-peptides. Results: Of all possible specificities of immature T cells entering the thymus, only a small fraction is actually selected for maturation. Monte Carlo simulations of thymocytes selection in the thymus are performed varying the size of the self and a parameter determining the number of encounter with antigen-presenting cells (APCs). We score the fraction of self-reacting thymocytes leaving the thymus as mature naive T cells and show that self-reactivity is only marginally dependent on the number of self-molecules presented by APCs, while it is strongly affected by a parameter proportional to the time spent in the thymus. We study how this measure changes when we vary the number of MHC alleles and found an optimal number not too different from what we have in reality. The main result of this study is more methodological than biological as we show that immunoinformatics data and methods can be used in systemic level simulation of immune processes.

Does intra-individual major histocompatibility complex diversity keep a golden mean?

An adaptive immune response is usually initiated only if a major histocompatibility complex (MHC) molecule presents pathogen-derived peptides to T-cells. Every MHC molecule can present only peptides that match its peptide-binding groove. Thus, it seems advantageous for an individual to express many different MHC molecules to be able to resist many different pathogens. However, although MHC genes are the most polymorphic genes of vertebrates, each individual has only a very small subset of the diversity at the population level. This is an evolutionary paradox. We provide an overview of the current data on infection studies and mate-choice experiments and conclude that overall evidence suggests that intermediate intra-individual MHC diversity is optimal. Selective forces that may set an upper limit to intra-individual MHC diversity are discussed. An updated mathematical model based on recent findings on T-cell selection can predict the natural range of intra-individual MHC diversity. Thus, the aim of our review is to evaluate whether the number of MHC alleles usually present in individuals may be optimal to balance the advantages of presenting an increased range of peptides versus the disadvantages of an increased loss of T-cells.

Spatial pattern of MHC class II variation in the great snipe (Gallinago media)

The genes of the major histocompatibility complex (MHC) code for proteins involved in antigen recognition and triggering of the adaptive immune response, and are therefore likely to be under selection from parasites. These selection regimes may vary in space and time. Here we report a strong geographical structure in MHC class II B genes of a migrating bird, the great snipe (Gallinago media). Genetic differentiation in the MHC between two ecologically distinct distributional regions (Scandinavian mountain populations vs. East European lowland populations) was still present after statistically controlling for the effect of selectively neutral variation (microsatellites) using partial Mantel tests. This suggests a role for selection in generating this spatial structure and that it represents local adaptation to different environments. Differentiation between populations within the two regions was negligible. Overall, we found a high number of MHC alleles (50, from 175 individuals). This, together with a tendency for a higher rate of nonsynonymous than synonymous substitutions in the peptide binding sites, and high Tajima's D in certain regions of the gene, suggests a history of balancing selection. MHC variation is often thought to be maintained by some form of balancing selection, but the nature of this selection remains unclear. Our results support the hypothesis that spatial variation in selection regimes contributes to the high polymorphism.