Multiple parasites mediate balancing selection at two MHC class II genes in the fossorial water vole: insights from multivariate analyses and population genetics

We investigated the factors mediating selection acting on two MHC class II genes (DQA and DRB) in water vole (Arvicola scherman) natural populations in the French Jura Mountains. Population genetics showed significant homogeneity in allelic frequencies at the DQA1 locus as opposed to neutral markers (nine microsatellites), indicating balancing selection acting on this gene. Moreover, almost exhaustive screening for parasites, including gastrointestinal helminths, brain coccidia and antibodies against viruses responsible for zoonoses, was carried out. We applied a co-inertia approach to the genetic and parasitological data sets to avoid statistical problems related to multiple testing. Two alleles, Arte-DRB-11 and Arte-DRB-15, displayed antagonistic associations with the nematode Trichuris arvicolae, revealing the potential parasite-mediated selection acting on DRB locus. Selection mechanisms acting on the two MHC class II genes thus appeared different. Moreover, overdominance as balancing selection mechanism was showed highly unlikely in this system.     

Effects of habitat fragmentation and changes of dispersal behaviour after a recent population decline on the genetic variability of noncoding and coding DNA of a monogamous Malagasy rodent

While interactions among demography, behaviour and genetic structure are well-documented for neutral genetic markers, the role of these parameters and the effects of genetic drift and selection are considerably less well understood in functional genes, such as the major histocompatibility complex (MHC). In this study, the consequences of habitat fragmentation and the effects of a current population decline on noncoding (mitochondrial DNA) and two coding MHC loci (DQA, DRB) with different functional importance were investigated in the small remnant subdivided population of the endangered Malagasy giant jumping rat (Hypogeomys antimena). Both neutral and selective markers revealed a significant genetic differentiation between the two remnant subpopulations. The FST values were much lower in the MHC DQA and DRB genes than in the mitochondrial data. The MHC DRB loci display the effects of both balancing selection (high sequence diversity, four times higher nonsynonymous than synonymous substitutions in the functionally important antigen-binding site positions, twice the average heterozygosity of individual amino acids at the positions identified as part of the antigen-binding site (ABS) than those outside the ABS and nonselective forces including genetic drift. Simultaneously with a current population decline offspring reduced their dispersal distances. No substantial effects were detected within the first 6 years of reduced gene flow in either mitochondrial or MHC markers.     

Adaptive and neutral genetic differentiation among Scottish and endangered Irish red grouse (<Emphasis Type="Italic">Lagopus lagopus scotica</Emphasis>)

Studying patterns of intra-specific genetic variation among populations allows for a better understanding of population structure and local adaptation. However, those patterns may differ according to the genetic markers applied, as neutral genetic markers reflect demographic processes and random genetic drift, whereas adaptive markers also carry the footprint of selection. In combination, neutral and adaptive genetic markers permit to assess the relative roles of drift and selection in shaping population structure. Among the best understood adaptive genetic loci are the genes of the major histocompatibility complex (MHC). We here study variation and differentiation at neutral SNP markers and MHC class II genes in red grouse (Lagopus lagopus scotica) from Ireland and Scotland. Irish red grouse populations are fragmented and drastically declining, but red grouse are abundant in Scotland. We find evidence for positive selection acting on the MHC genes and variation in MHC gene copy numbers among Irish individuals. Furthermore, there was significant population differentiation among red grouse from Ireland and Scotland at the neutral SNP markers (F_ST = 0.084) and the MHC-BLB genes (F_ST: BLB1 = 0.116, BLB2 = 0.090, BLB3 = 0.104). Differentiation at the MHC-BLB1 was significantly higher than at the neutral SNP markers, suggesting that selection plays an important role in shaping MHC variation, in addition to genetic drift. We speculate that the observed differentiation pattern might be due to local adaptation to different parasite regimes. These findings have strong conservation implications and we advise against the introduction of Scottish red grouse to supplement Irish populations.     

A temporal analysis shows major histocompatibility complex loci in the Scandinavian wolf population are consistent with neutral evolution

The major histocompatibility complex (MHC) has an integral role in the immune system, and hence diversity at its genes may be of particular importance for the health of populations. In large populations, balancing selection maintains diversity in MHC genes, but theoretical expectations indicate that this form of selection is absent or inefficient in small populations. We examine the level of diversity at three MHC class II loci in the wolf population of Scandinavia, a population naturally recolonized with a genetic contribution from as few as three founders, and in four neighbouring wolf populations. In the Scandinavian wolf population, two alleles were found for each locus and the distribution of alleles is compatible with their linkage into two haplotypes. Changes in the level of heterozygosity over time since recolonization demonstrate the effects of the proposed arrival of an immigrant wolf. The maintenance of diversity is shown to be compatible with a neutral, random allocation of alleles, in conjunction with crossing between packs. A total of 15 DRB1, seven DQA and 10 DQB1 alleles are found in four neighbouring wolf populations, with substantial sharing across populations. Even in these larger populations, bottlenecks and fragmentation with consequent genetic drift are likely to have resulted in few indicators for balancing selection and significant differentiation of populations.     

Genetic diversity and differentiation at MHC genes in island populations of tuatara (Sphenodon spp.)

Neutral genetic markers are commonly used to understand the effects of fragmentation and population bottlenecks on genetic variation in threatened species. Although neutral markers are useful for inferring population history, the analysis of functional genes is required to determine the significance of any observed geographical differences in variation. The genes of the major histocompatibility complex (MHC) are well‐known examples of genes of adaptive significance and are particularly relevant to conservation because of their role in pathogen resistance. In this study, we survey diversity at MHC class I loci across a range of tuatara populations. We compare the levels of MHC variation with that observed at neutral microsatellite markers to determine the relative roles of balancing selection, diversifying selection and genetic drift in shaping patterns of MHC variation in isolated populations. In general, levels of MHC variation within tuatara populations are concordant with microsatellite variation. Tuatara populations are highly differentiated at MHC genes, particularly between the northern and Cook Strait regions, and a trend towards diversifying selection across populations was observed. However, overall our results indicate that population bottlenecks and isolation have a larger influence on patterns of MHC variation in tuatara populations than selection.     

Trans-species polymorphism and evidence of selection on class II MHC loci in tuco-tucos (Rodentia: Ctenomyidae)

Balancing selection acting over the evolutionary history of a lineage can result in the retention of alleles among species for longer than expected under neutral evolution. The associated pattern of trans-species polymorphism, in which similar or even identical alleles are shared among species, is often used to infer that balancing selection has occurred. The genes of the major histocompatibility complex (MHC) are thought to be subject to balancing selection that maintains alleles associated with response to specific pathogens. To explore the role of balancing selection in shaping MHC diversity in ctenomyid rodents, we examined allelic variability at the class II DRB and DQA loci in 18 species in the genus Ctenomys. Previous studies of four of these species had revealed significant within-population evidence of positive selection on MHC loci. The current study expands upon these analyses to (1) evaluate among-species evidence of positive selection and (2) explore the potential for balancing selection on MHC genes. Interspecific nucleotide sequence variation revealed significant evidence of positive selection on the DRB and DQA loci. At the same time, comparisons of phylogenetic trees for these MHC loci with a putative species tree based on mitochondrial sequence data revealed multiple examples of trans-specific polymorphism, including sharing of identical DRB and DQA alleles among distantly related species of Ctenomys. These findings suggest that MHC genes in these animals have historically been subject to balancing selection and yield new insights into the complex suite of forces shaping MHC diversity in free-living vertebrates.     

Genetic structure in insular and mainland populations of house sparrows (Passer domesticus) and their hemosporidian parasites

Small and isolated populations usually exhibit low levels of genetic variability, and thus, they are expected to have a lower capacity to adapt to changes in environmental conditions, such as exposure to pathogens and parasites. Comparing the genetic variability of selectively neutral versus functional loci allows one to assess the evolutionary history of populations and their future evolutionary potential. The genes of the major histocompatibility complex (MHC) control immune recognition of parasites, and their unusually high diversity is genes which is likely driven by parasite‐mediated balancing selection. Here, we examined diversity and differentiation of neutral microsatellite loci and functional MHC class I genes in house sparrows (Passer domesticus), living in six insular and six mainland populations, and we aimed to determine whether their diversity or differentiation correlates with the diversity and the prevalence of infection of hemosporidian parasites. We found that island bird populations tended to have lower neutral genetic variability, whereas MHC variability gene was similar between island and mainland populations. Similarly, island populations tended to show greater genetic differentiation than mainland populations, especially at microsatellite markers. The maintenance of MHC genetic diversity and its less marked structure in the island populations could be attributed to balancing‐selection. The greater MHC differentiation among populations was negatively correlated with similarity in blood parasites (prevalence and diversity of parasite strains) between populations. Even at low prevalence and small geographical scale, haemosporidian parasites might contribute to structure the variability of immune genes among populations of hosts.     

Substantial functional diversity accompanies limited major histocompatibility complex class II variability in golden jackal (Canis aureus): A comparison between two wild Canis species in Croatia

The golden jackal (Canis aureus) is one of the less studied carnivores and research on its major histocompatibility complex (MHC) variability is just at its early stages. MHC genes encode cell-surface receptors that serve to bind and present antigens to T cells, which is essential to initiating specific immunological responses in vertebrates. In this paper we present for the first time patterns of genetic diversity and natural selection on MHC class II DLA-DRB1, DQA1 and DQB1 loci in the golden jackal using samples from two geographically distinct regions in Croatia and further compare them to the values found in its congener grey wolf (Canis lupus). Diversity of golden jackals at all three loci was markedly lower than that of grey wolves (allelic richness values were 4, 2 and 3 in jackal versus 11.9, 6.6 and 10.2 in wolves for DRB1, DQA1 and DQB1, respectively) and can be attributed to a genetic drift rather than to the lack of historical positive selection. The finding of high evolutionary distances (16.3% for DRB1 and 8.5% for DQB1) and a substantial number of codons predicted to be under the influence of positive selection (11 for DRB1 and 9 for DQB1) suggests that the investigated golden jackal population still contains considerable functional diversity necessary for the presentation of varied foreign peptides. In contrast to neutral genetic variation, our results suggest that the Dalmatian population has a higher MHC diversity than the Slavonian population, casting doubt on its supposed isolation and calling for a more extensive investigation of the MHC variability of southern Balkan jackal populations.     

Allelic diversity at the Mhc-DQA locus of woodmouse populations (Apodemus sylvaticus) present in the islands and mainland of the northern Mediterranean

Aim Polymorphism at neutral markers and at MHC loci in rodent populations living on islands is generally low. The main genetic factors that may contribute to a reduced level of genetic variability are genetic drift, reduced gene flow and founder events. We investigated the pattern of polymorphism at the second exon of the Mhc‐DQA gene in island populations of Apodemus sylvaticus and in their mainland counterparts to investigate the pattern of MHC polymorphism in a phylogeographical context and to assess the impact of insularity on diversity at this locus. Location Eight north Mediterranean populations of Apodemus sylvaticus were studied, including five island populations (Majorca, Minorca, Porquerolles, Port‐Cros and Sicily) and three mainland populations. Methods cDNA sequencing and nucleotide sequences analyses. Synonymous and non‐synonymous substitutions were examined at the PBR and non‐PBR sites. The DQA allelic distribution in populations was compared with the woodmouse phylogeography. Results This study presents novel DQA alleles. High polymorphism of the DQA locus is recorded in natural populations of A. sylvaticus with 13 alleles being widely distributed irrespective of the geographical origin and palaeoclimatic history of populations. The DQA locus does not show the expected pattern for non‐synonymous substitutions at the PBR sites. However, island populations show a weak loss of polymorphism in comparison with their mainland counterparts. Main conclusions The DQA locus in the woodmouse seems to be subject to weak selection and does not allow resolution of phylogeographical relationships among European woodmouse populations. The presence of at least three alleles in island populations and the maintenance of five alleles between the two European lineages over 1.5 Myr suggest that balancing selection may act within populations, and more precisely within island populations, to maintain genetic variability. This study shows that phylogeographical studies are a prerequisite for any genetic investigation of selected genes in natural populations.     

Major histocompatibility complex class II genetic variation in forest musk deer (Moschus berezovskii) in China

The major histocompatibility complex (MHC) plays an important role in the immune system of vertebrates. We used the second exon of four MHC class II genes (DRA, DQA1, DQA2 and DRB3) to assess the overall MHC variation in forest musk deer (Moschus berezovskii). We also compared the MHC variation in captive and wild populations. We observed 22 alleles at four loci (four at DRA, four at DQA1, four at DQA2 and 10 at DRB3), 15 of which were newly identified alleles. Results suggest that forest musk deer maintain relatively high MHC variation, which may result from balancing selection. Moreover, considerable diversity was observed at the DRA locus. We found a high frequency of Mobe‐DRA*02, Mobe‐DQA1*01 and Mobe‐DQA2*05 alleles, which may be important for pathogen resistance. A Ewens–Watterson test showed that the DRB3 locus in the wild population had experienced recent balancing selection. We detected a small divergence at the DRA locus, suggesting the effect of weak positive selection on the DRA gene. Alternatively, this locus may be young and not yet adapted a wide spectrum of alleles for pathogen resistance. The significant heterozygosity deficit observed at the DQA1 and DRB3 loci in the captive population and at all four loci in the wild population may be the result of a population bottleneck. Additionally, MHC genetic diversity was higher in the wild population than in the captive, suggesting that the wild population may have the ability to respond to a wider range of pathogens.     

Can balancing selection on MHC loci counteract genetic drift in small fragmented populations of black grouse?

The ability of natural populations to adapt to new environmental conditions is crucial for their survival and partly determined by the standing genetic variation in each population. Populations with higher genetic diversity are more likely to contain individuals that are better adapted to new circumstances than populations with lower genetic diversity. Here, we use both neutral and major histocompatibility complex (MHC) markers to test whether small and highly fragmented populations hold lower genetic diversity than large ones. We use black grouse as it is distributed across Europe and found in populations with varying degrees of isolation and size. We sampled 11 different populations; five continuous, three isolated, and three small and isolated. We tested patterns of genetic variation in these populations using three different types of genetic markers: nine microsatellites and 21 single nucleotide polymorphisms (SNPs) which both were found to be neutral, and two functional MHC genes that are presumably under selection. The small isolated populations displayed significantly lower neutral genetic diversity compared to continuous populations. A similar trend, but not as pronounced, was found for genotypes at MHC class II loci. Populations were less divergent at MHC genes compared to neutral markers. Measures of genetic diversity and population genetic structure were positively correlated among microsatellites and SNPs, but none of them were correlated to MHC when comparing all populations. Our results suggest that balancing selection at MHC loci does not counteract the power of genetic drift when populations get small and fragmented.     

Neutral versus adaptive genetic variation in parasite resistance: importance of major histocompatibility complex supertypes in a free-ranging primate

Current discussions in evolutionary ecology and conservation genetics focus on the relative importance of using selective neutral markers or markers of coding genes to identify adaptive and evolutionary relevant processes. Genetic diversity might be particularly important in immune genes (e.g., in genes of the major histocompatibility complex, MHC), which are influencing pathogen and parasite resistance. We investigated the effects of neutral versus adaptive genetic variation in parasite resistance in a natural population of fat-tailed dwarf lemurs (Cheirogaleus medius). No association between neutral overall individual genetic diversity and parasite load could be detected. In 149 individuals, we identified 50 MHC class II alleles of the functionally important duplicated DRB locus. The investigation of the functional importance of immune gene (MHC) diversity and parasite selection in natural populations is often problematic due to extensive polymorphism in the MHC genes and restrictions in available sample sizes. Here, for the first time we applied an approach that has been developed in human medical studies. Eleven MHC class II supertypes were identified based on shared antigen-binding similarities. The number of individual MHC supertypes had no influence on the nematode burden. However, we found evidence for a specific MHC supertype (supertype 1) that was linked to infected individuals, a higher number of different nematode infections and high intensity of infection per individual. Moreover, one rare MHC supertype (supertype 7) was revealed to be advantageous with respect to parasite burden. Thus, our results add evidence to the small body of studies that show significant associations between specific MHC constitutions and naturally occurring parasites in the complexity of natural populations.     

Geographic variation of the major histocompatibility complex in Eastern Atlantic grey seals (Halichoerus grypus)

Pathogen-driven balancing selection maintains high genetic diversity in many vertebrates, particularly in the major histocompatibility complex (MHC) immune system gene family, which is often associated with disease susceptibility. In large natural populations where subpopulations face different pathogen pressures, the MHC should show greater genetic differentiation within a species than neutral markers. We examined genetic diversity at the MHC-DQB locus and nine putatively neutral microsatellite markers in grey seals (Halichoerus grypus) from eight United Kingdom (UK) colonies, the Faeroe Islands and Sable Island, Canada. Five DQB alleles were identified in grey seals, which varied in prevalence across the grey seal range. Among the seal colonies, significant differences in DQB allele and haplotype frequencies and in average DQB heterozygosity were observed. Additionally, the DQB gene exhibited greater differentiation among colonies compared with neutral markers, yet a weaker pattern of isolation by distance (IBD). After correcting for the underlying IBD pattern, subpopulations breeding in similar habitats were more similar to one another in DQB allele frequencies than populations breeding in different habitats, but the same did not hold true for microsatellites, suggesting that habitat-specific pathogen pressure influences MHC evolution. Overall, the data are consistent with selection at MHC-DQB loci in grey seals with both varying selective pressures and geographic population structure appearing to influence the DQB genetic composition of breeding colonies.     

Population fragmentation and major histocompatibility complex variation in the spotted suslik,Spermophilus suslicus

The fragmentation of populations typically enhances depletion of genetic variation, but highly polymorphic major histocompatibility complex (MHC) genes are thought to be under balancing selection and therefore retain polymorphism despite population bottlenecks. In this study, we investigate MHC DRB (class II) exon 2 variation in 14 spotted suslik populations from two regions differing in their degree of habitat fragmentation and gene flow. We found 16 alleles that segregated in a sample of 248 individuals. The alleles were highly divergent and revealed the hallmark signs of positive selection acting on them in the past, showing a significant excess of nonsynonymous substitutions. This excess was concentrated in putative antigen‐binding sites, which suggests that past selection was driven by pathogens. MHC diversity was significantly lower in fragmented western populations than in the eastern populations, characterized by significant gene flow. In contrast to neutral variation, amova did not reveal genetic differentiation between the two regions. This may indicate similar selective pressures shaping MHC variation in both regions until the recent past. However, MHC allelic richness within a population was correlated with that for microsatellites. F_ST outlier analyses have shown that population differentiation at DRB was neither higher nor lower than expected under neutrality. The results suggest that selection on MHC is not strong enough to counteract drift that results from recent fragmentation of spotted suslik populations.     

On the relative roles of selection and genetic drift in shaping MHC variation

Genes of the major histocompatibility complex (MHC) have provided some of the clearest examples of how natural selection generates discordances between adaptive and neutral variation in natural populations. The type and intensity of selection as well as the strength of genetic drift are believed to be important in shaping the resulting pattern of MHC diversity. However, evaluating the relative contribution of multiple microevolutionary forces is challenging, and empirical studies have reported contrasting results. For instance, balancing selection has been invoked to explain high levels of MHC diversity and low population differentiation in comparison with other nuclear markers. Other studies have shown that genetic drift can sometimes overcome selection and then patterns of genetic variation at adaptive loci cannot be discerned from those occurring at neutral markers. Both empirical and simulated data also indicate that loss of genetic diversity at adaptive loci can occur faster than at neutral loci when selection and population bottlenecks act simultaneously. Diversifying selection, on the other hand, explains accelerated MHC divergence as the result of spatial variation in pathogen‐mediated selective regimes. Because of all these possible scenarios and outcomes, collecting information from as many study systems as possible, is crucial to enhance our understanding about the evolutionary forces driving MHC polymorphism. In this issue, Miller and co‐workers present an illuminating contribution by combining neutral markers (microsatellites) and adaptive MHC class I loci during the investigation of genetic differentiation across island populations of tuatara Sphenodon punctatus. Their study of geographical variation reveals a major role of genetic drift in shaping MHC variation, yet they also discuss some support for diversifying selection.     

No evidence for MHC‐based mate choice in wild giant pandas

Major histocompatibility complex genes (MHC), a gene cluster that controls the immune response to parasites, are regarded as an important determinant of mate choice. However, MHC‐based mate choice studies are especially rare for endangered animals. The giant panda (Ailuropoda melanoleuca), a flagship species, has suffered habitat loss and fragmentation. We investigated the genetic variation of three MHC class II loci, including DRB1, DQA1, and DQA2, for 19 mating‐pairs and 11 parent‐pairs of wild giant pandas based on long‐term field behavior observations and genetic samples. We tested four hypotheses of mate choice based on this MHC variation. We found no supporting evidence for the MHC‐based heterosis, genetic diversity, genetic compatibility and “good gene” hypotheses. These results suggest that giant pandas may not use MHC‐based signals to select mating partners, probably because limited mating opportunities or female‐biased natal dispersal restricts selection for MHC‐based mate choice, acknowledging the caveat of the small sample size often encountered in endangered animal studies. Our study provides insight into the mate choice mechanisms of wild giant pandas and highlights the need to increase the connectivity and facilitate dispersal among fragmented populations and habitats.     

Spatial and temporal patterns of neutral and adaptive genetic variation in the endangered African wild dog (Lycaon pictus)

Deciphering patterns of genetic variation within a species is essential for understanding population structure, local adaptation and differences in diversity between populations. Whilst neutrally evolving genetic markers can be used to elucidate demographic processes and genetic structure, they are not subject to selection and therefore are not informative about patterns of adaptive variation. As such, assessments of pertinent adaptive loci, such as the immunity genes of the major histocompatibility complex (MHC), are increasingly being incorporated into genetic studies. In this study, we combined neutral (microsatellite, mtDNA) and adaptive (MHC class II DLA‐DRB1 locus) markers to elucidate the factors influencing patterns of genetic variation in the African wild dog (Lycaon pictus); an endangered canid that has suffered extensive declines in distribution and abundance. Our genetic analyses found all extant wild dog populations to be relatively small (N_e < 30). Furthermore, through coalescent modelling, we detected a genetic signature of a recent and substantial demographic decline, which correlates with human expansion, but contrasts with findings in some other African mammals. We found strong structuring of wild dog populations, indicating the negative influence of extensive habitat fragmentation and loss of gene flow between habitat patches. Across populations, we found that the spatial and temporal structure of microsatellite diversity and MHC diversity were correlated and strongly influenced by demographic stability and population size, indicating the effects of genetic drift in these small populations. Despite this correlation, we detected signatures of selection at the MHC, implying that selection has not been completely overwhelmed by genetic drift.     

Fluctuating Selection,Egg Banks and Population Genetic Structure in Cyclically Parthenogenetic Species

Associations between neutral genetic markers and genes under selection have been suggested to explain the population genetic structure of neutral genes in cyclically parthenogenetic freshwater invertebrates. A simulation model was constructed in order to analyse the extrapolated consequences of observed fluctuations in genotype frequencies in Daphnia, in the presence of egg banks. When of sufficient depth and magnitude, egg banks in combination with fluctuating selection were shown to maintain genetic variation within populations indefinitely. The level of equilibrium diversity increased with the depth and magnitude of the banks, and with intensity of selection. The same threshold was responsible for genetic differentiation between populations, which was independent of migration rate, and which was attained very rapidly following initial Hardy–Weinberg equilibrium. In the absence of selection, egg banks increased the effective size of local populations, thereby decreasing genetic differentiation at migration-drift equilibrium. These results suggest that egg banks are crucial to the genetic structure in the presence of fluctuating selective pressures, but more data are needed if this knowledge is to be used in an improved general understanding of the genetic structure of cyclically parthenogenetic species.     

Selective pressures on MHC class II genes in the guppy (Poecilia reticulata) as inferred by hierarchical analysis of population structure

Genes of the major histocompatibility complex, which are the most polymorphic of all vertebrate genes, are a pre‐eminent system for the study of selective pressures that arise from host–pathogen interactions. Balancing selection capable of maintaining high polymorphism should lead to the homogenization of MHC allele frequencies among populations, but there is some evidence to suggest that diversifying selection also operates on the MHC. However, the pattern of population structure observed at MHC loci is likely to depend on the spatial and/or temporal scale examined. Here, we investigated selection acting on MHC genes at different geographic scales using Venezuelan guppy populations inhabiting four regions. We found a significant correlation between MHC and microsatellite allelic richness across populations, which suggests the role of genetic drift in shaping MHC diversity. However, compared to microsatellites, more MHC variation was explained by differences between populations within larger geographic regions and less by the differences between the regions. Furthermore, among proximate populations, variation in MHC allele frequencies was significantly higher compared to microsatellites, indicating that selection acting on MHC may increase population structure at small spatial scales. However, in populations that have significantly diverged at neutral markers, the population‐genetic signature of diversifying selection may be eradicated in the long term by that of balancing selection, which acts to preserve rare alleles and thus maintain a common pool of MHC alleles.     

Unraveling the Effects of Selection and Demography on Immune Gene Variation in Free-Ranging Plains Zebra (Equus quagga) Populations

Demography, migration and natural selection are predominant processes affecting the distribution of genetic variation among natural populations. Many studies use neutral genetic markers to make inferences about population history. However, the investigation of functional coding loci, which directly reflect fitness, is critical to our understanding of species'' ecology and evolution. Immune genes, such as those of the Major Histocompatibility Complex (MHC), play an important role in pathogen recognition and provide a potent model system for studying selection. We contrasted diversity patterns of neutral data with MHC loci, ELA-DRA and -DQA, in two southern African plains zebra (Equus quagga) populations: Etosha National Park, Namibia, and Kruger National Park, South Africa. Results from neutrality tests, along with observations of elevated diversity and low differentiation across populations, supported previous genus-level evidence for balancing selection at these loci. Despite being low, MHC divergence across populations was significant and may be attributed to drift effects typical of geographically separated populations experiencing little to no gene flow, or alternatively to shifting allele frequency distributions driven by spatially variable and fluctuating pathogen communities. At the DRA, zebra exhibited geographic differentiation concordant with microsatellites and reduced levels of diversity in Etosha due to highly skewed allele frequencies that could not be explained by demography, suggestive of spatially heterogeneous selection and local adaptation. This study highlights the complexity in which selection affects immune gene diversity and warrants the need for further research on the ecological mechanisms shaping patterns of adaptive variation among natural populations.