Plasmodium relictum infection and MHC diversity in the house sparrow (Passer domesticus)

Antagonistic coevolution between hosts and parasites has been proposed as a mechanism maintaining genetic diversity in both host and parasite populations. In particular, the high level of genetic diversity usually observed at the major histocompatibility complex (MHC) is generally thought to be maintained by parasite-driven selection. Among the possible ways through which parasites can maintain MHC diversity, diversifying selection has received relatively less attention. This hypothesis is based on the idea that parasites exert spatially variable selection pressures because of heterogeneity in parasite genetic structure, abundance or virulence. Variable selection pressures should select for different host allelic lineages resulting in population-specific associations between MHC alleles and risk of infection. In this study, we took advantage of a large survey of avian malaria in 13 populations of the house sparrow (Passer domesticus) to test this hypothesis. We found that (i) several MHC alleles were either associated with increased or decreased risk to be infected with Plasmodium relictum, (ii) the effects were population specific, and (iii) some alleles had antagonistic effects across populations. Overall, these results support the hypothesis that diversifying selection in space can maintain MHC variation and suggest a pattern of local adaptation where MHC alleles are selected at the local host population level.     

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.     

Contrasting patterns of selection and drift between two categories of immune genes in prairie‐chickens

Immune‐receptor genes of the adaptive immune system, such as the major histocompatibility complex (MHC), are involved in recognizing specific pathogens and are known to have high rates of adaptive evolution, presumably as a consequence of rapid co‐evolution between hosts and pathogens. In contrast, many ‘mediating’ genes of the immune system do not interact directly with specific pathogens and are involved in signalling (e.g. cytokines) or controlling immune cell growth. As a consequence, we might expect stronger selection at immune‐receptor than mediating genes, but these two types of genes have not been compared directly in wild populations. Here, we tested the hypothesis that selection differs between MHC (class I and II) and mediating genes by comparing levels of population differentiation across the range of greater prairie‐chickens (Tympanuchus cupido). As predicted, there was stronger population differentiation and isolation by distance at immune receptor (MHC) than at either mediating genes or neutral microsatellites, suggesting a stronger role of local adaptation at the MHC. In contrast, mediating genes displayed weaker differentiation between populations than neutral microsatellites, consistent with selection favouring similar alleles across populations for mediating genes. In addition to selection, drift also had a stronger effect on immune receptor (MHC) than mediating genes as indicated by the stronger decline of MHC variation in relation to population size. This is the first study in the wild to show that the effects of selection and drift on immune genes vary across populations depending on their functional role.     

Comparative analysis of population structure across environments and geographical scales at major histocompatibility complex and microsatellite loci in Atlantic salmon (Salmo salar)

Evidence of selection acting on major histocompatibility complex (MHC) genes has been illustrated with the analysis of their nucleotide sequences and allele frequency distribution. Comparing the patterns of population differentiation at neutral markers and MHC genes in the wild may provide further insights about the relative role of selection and neutrality in shaping their diversity. In this study, we combine both methods to assess the role of selection on a MHC gene in Atlantic salmon. We compare variation at a MHC class II B locus and microsatellites among 14 samples from seven different rivers and seven subpopulations within a single river system covering a variety of habitats and different geographical scales. We show that diversifying selection is acting on the sites involved in antigen presentation and that balancing selection maintains a high level of polymorphism within populations. Despite important differences in habitat type, the comparison of the population structure at MHC and microsatellites on large geographical scales reveals a correlation between patterns of differentiation, indicating that drift and migration have been more important than selection in shaping population differentiation at the MHC locus. In contrast, strong discrepancies between patterns of population differentiation at the two types of markers provides support for the role of selection in shaping population structure within rivers. Together, these results confirm that natural selection is influencing MHC gene diversity in wild Atlantic salmon although neutral forces may also be important in their evolution.     

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.     

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.     

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.     

Contrasting patterns of selection between MHC I and II across populations of Humboldt and Magellanic penguins

The evolutionary and adaptive potential of populations or species facing an emerging infectious disease depends on their genetic diversity in genes, such as the major histocompatibility complex (MHC). In birds, MHC class I deals predominantly with intracellular infections (e.g., viruses) and MHC class II with extracellular infections (e.g., bacteria). Therefore, patterns of MHC I and II diversity may differ between species and across populations of species depending on the relative effect of local and global environmental selective pressures, genetic drift, and gene flow. We hypothesize that high gene flow among populations of Humboldt and Magellanic penguins limits local adaptation in MHC I and MHC II, and signatures of selection differ between markers, locations, and species. We evaluated the MHC I and II diversity using 454 next‐generation sequencing of 100 Humboldt and 75 Magellanic penguins from seven different breeding colonies. Higher genetic diversity was observed in MHC I than MHC II for both species, explained by more than one MHC I loci identified. Large population sizes, high gene flow, and/or similar selection pressures maintain diversity but limit local adaptation in MHC I. A pattern of isolation by distance was observed for MHC II for Humboldt penguin suggesting local adaptation, mainly on the northernmost studied locality. Furthermore, trans‐species alleles were found due to a recent speciation for the genus or convergent evolution. High MHC I and MHC II gene diversity described is extremely advantageous for the long‐term survival of the species.     

TEMPORAL VARIATION AT THE MHC CLASS IIB IN WILD POPULATIONS OF THE GUPPY (POECILIA RETICULATA)

Understanding genetic diversity in natural populations is a fundamental objective of evolutionary biology. The immune genes of the major histocompatibility complex (MHC) are excellent candidates to study such diversity because they are highly polymorphic in populations. Although balancing selection may be responsible for maintaining diversity at these functionally important loci, temporal variation in selection pressure has rarely been examined. We examine temporal variation in MHC class IIB diversity in nine guppy (Poecilia reticulata) populations over two years. We found that five of the populations changed significantly more at the MHC than at neutral (microsatellite) loci as measured by F_ST, which suggests that the change at the MHC was due to selection and not neutral processes. Additionally, pairwise population differentiation measures at the MHC were higher in 2007 than in 2006, with the signature of selection changing from homogenizing to diversifying selection or neutral evolution. Interestingly, within the populations the magnitude of the change at the MHC between years was related to the change in the proportion of individuals infected by a common parasite, indicating a link between genetic structure and the parasite. Our data thereby implicate temporal variation in selective pressure as an important mechanism maintaining diversity at the MHC in wild populations.     

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.     

Pathogen richness and abundance predict patterns of adaptive major histocompatibility complex variation in insular amphibians

The identification of the factors responsible for genetic variation and differentiation at adaptive loci can provide important insights into the evolutionary process and is crucial for the effective management of threatened species. We studied the impact of environmental viral richness and abundance on functional diversity and differentiation of the MHC class Ia locus in populations of the black‐spotted pond frog (Pelophylax nigromaculatus), an IUCN‐listed species, on 24 land‐bridge islands of the Zhoushan Archipelago and three nearby mainland sites. We found a high proportion of private MHC alleles in mainland and insular populations, corresponding to 32 distinct functional supertypes, and strong positive selection on MHC antigen‐binding sites in all populations. Viral pathogen diversity and abundance were reduced at island sites relative to the mainland, and islands housed distinctive viral communities. Standardized MHC diversity at island sites exceeded that found at neutral microsatellites, and the representation of key functional supertypes was positively correlated with the abundance of specific viruses in the environment (Frog virus 3 and Ambystoma tigrinum virus). These results indicate that pathogen‐driven diversifying selection can play an important role in maintaining functionally important MHC variation following island isolation, highlighting the importance of considering functionally important genetic variation and host–pathogen associations in conservation planning and management.     

Variation in MHC genotypes in two populations of house sparrow (Passer domesticus) with different population histories

Small populations are likely to have a low genetic ability for disease resistance due to loss of genetic variation through inbreeding and genetic drift. In vertebrates, the highest genetic diversity of the immune system is located at genes within the major histocompatibility complex (MHC). Interestingly, parasite‐mediated selection is thought to potentially maintain variation at MHC loci even in populations that are monomorphic at other loci. Therefore, general loss of genetic variation in the genome may not necessarily be associated with low variation at MHC loci. We evaluated inter‐ and intrapopulation variation in MHC genotypes between an inbred (Aldra) and a relatively outbred population (Hestmannøy) of house sparrows (Passer domesticus) in a metapopulation at Helgeland, Norway. Genomic (gDNA) and transcribed (cDNA) alleles of functional MHC class I and IIB loci, along with neutral noncoding microsatellite markers, were analyzed to obtain relevant estimates of genetic variation. We found lower allelic richness in microsatellites in the inbred population, but high genetic variation in MHC class I and IIB loci in both populations. This suggests that also the inbred population could be under balancing selection to maintain genetic variation for pathogen resistance.     

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.     

Spatio-temporal variation in the strength and mode of selection acting on major histocompatibility complex diversity in water vole (Arvicola terrestris) metapopulations

Patterns of spatio-temporal genetic variation at a class II major histocompatibility complex (MHC) locus and multiple microsatellite loci were analysed within and between three water vole metapopulations in Scotland, UK. Comparisons of MHC and microsatellite spatial genetic differentiation, based on standardised tests between two demographically asynchronous zones within a metapopulation, suggested that spatial MHC variation was affected by balancing selection, directional selection and random genetic drift, but that the relative effects of these microevolutionary forces vary temporally. At the metapopulation level, between-year differentiation for MHC loci was significantly correlated with that of microsatellites, signifying that neutral factors such as migration and drift were primarily responsible for overall temporal genetic change at the metapopulation scale. Between metapopulations, patterns of genetic differentiation implied that, at large spatial scales, MHC variation was primarily affected by directional selection and drift. Levels of MHC heterozygosity in excess of Hardy–Weinberg expectations were consistent with overdominant balancing selection operating on MHC variation within metapopulations. However, this effect was not constant among all samples, indicating temporal variation in the strength of selection relative to other factors. The results highlight the benefit of contrasting variation at MHC with neutral markers to separate the effects of stochastic and deterministic microevolutionary forces, and add to a growing body of evidence showing that the mode and relative strength of selection acting on MHC diversity varies both spatially and temporally.     

Adaptive and Neutral Genetic Variation and Colonization History of Atlantic Salmon, Salmo salar

Synopsis I combined neutral microsatellite markers with the major histocompatibility complex (MHC) class IIB to study genetic differentiation and colonization history in Atlantic salmon, Salmo salar, in the Baltic Sea and in the north-eastern Atlantic. Baltic salmon populations have lower levels of microsatellite genetic variation, in terms of heterozygosity and allelic richness than Atlantic populations, confirming earlier findings with other genetic markers, suggesting that the Baltic Sea populations have been exposed to genetic bottlenecks, most likely at a founding event. On the other hand, the level of MHC variation was similar in the Baltic and in the north-eastern Atlantic, indicating that positive balancing selection has increased the level of MHC-variation. Both microsatellite and MHC class IIB genetic variation give strong support to the hypothesis that the Baltic salmon are of a biphyletic origin, the southern population in this study is strongly differentiated from both the northern Baltic salmon populations and from the north-eastern Atlantic populations. Salmon may have colonized the northern Baltic Sea either from the south, via the so called “N?rke strait” or from the north, via a proposed historical connection between the White Sea and the northern Baltic. At microsatellites, no significant isolation-by distance was found at either colonization route. At the MHC, populations were significantly isolated by distance when assuming that colonization occurred via the “N?rke strait”.     

Genetic variation at MHC, mitochondrial and microsatellite loci in isolated populations of Brown trout (Salmo trutta)

We have studied levels and distribution of genetic variation in nine isolated populations of Brown trout in NW Spain. In the present study, we have tried to test the importance of preservation of genetic variability for the survival of a set of isolated Brown trout (Salmo trutta) populations from the same river drainage. We screened genetic variation in three different markers, mitochondrial, microsatellites and Major Histocompatibility Complex (MHC), presumed to be under different selective pressures. Overall, genetic diversity varied considerably across populations and the distribution of genetic variation was similar at MHC and microsatellites; highly polymorphic populations at the microsatellite loci were also highly polymorphic at the MHC. We also observed high levels of differentiation among populations. Although we found evidence suggesting that balancing selection has influenced the long term evolution of the MHC, genetic drift seems to have eroded the effect of selection, becoming the predominant evolutionary force shaping genetic variation in some of the smaller populations. Despite current lack of variation at the MHC, these small populations seem to have remained viable for a long time.     

Contrasting epidemic histories reveal pathogen-mediated balancing selection on class II MHC diversity in a wild songbird

The extent to which pathogens maintain the extraordinary polymorphism at vertebrate Major Histocompatibility Complex (MHC) genes via balancing selection has intrigued evolutionary biologists for over half a century, but direct tests remain challenging. Here we examine whether a well-characterized epidemic of Mycoplasmal conjunctivitis resulted in balancing selection on class II MHC in a wild songbird host, the house finch (Carpodacus mexicanus). First, we confirmed the potential for pathogen-mediated balancing selection by experimentally demonstrating that house finches with intermediate to high multi-locus MHC diversity are more resistant to challenge with Mycoplasma gallisepticum. Second, we documented sequence and diversity-based signatures of pathogen-mediated balancing selection at class II MHC in exposed host populations that were absent in unexposed, control populations across an equivalent time period. Multi-locus MHC diversity significantly increased in exposed host populations following the epidemic despite initial compromised diversity levels from a recent introduction bottleneck in the exposed host range. We did not observe equivalent changes in allelic diversity or heterozygosity across eight neutral microsatellite loci, suggesting that the observations reflect selection rather than neutral demographic processes. Our results indicate that a virulent pathogen can exert sufficient balancing selection on class II MHC to rescue compromised levels of genetic variation for host resistance in a recently bottlenecked population. These results provide evidence for Haldane's long-standing hypothesis that pathogens directly contribute to the maintenance of the tremendous levels of genetic variation detected in natural populations of vertebrates.     

Clonality, genetic diversity and support for the diversifying selection hypothesis in natural populations of a flower-living yeast

Vast amounts of effort have been devoted to investigate patterns of genetic diversity and structuring in plants and animals, but similar information is scarce for organisms of other kingdoms. The study of the genetic structure of natural populations of wild yeasts can provide insights into the ecological and genetic correlates of clonality, and into the generality of recent hypotheses postulating that microbial populations lack the potential for genetic divergence and allopatric speciation. Ninety‐one isolates of the flower‐living yeast Metschnikowia gruessii from southeastern Spain were DNA fingerprinted using amplified fragment length polymorphism (AFLP) markers. Genetic diversity and structuring was investigated with band‐based methods and model‐ and nonmodel‐based clustering. Linkage disequilibrium tests were used to assess reproduction mode. Microsite‐dependent, diversifying selection was tested by comparing genetic characteristics of isolates from bumble bee vectors and different floral microsites. AFLP polymorphism (91%) and genotypic diversity were very high. Genetic diversity was spatially structured, as shown by amova (Φ_st = 0.155) and clustering. The null hypothesis of random mating was rejected, clonality seeming the prevailing reproductive mode in the populations studied. Genetic diversity of isolates declined from bumble bee mouthparts to floral microsites, and frequency of five AFLP markers varied significantly across floral microsites, thus supporting the hypothesis of diversifying selection on clonal lineages. Wild populations of clonal fungal microbes can exhibit levels of genetic diversity and spatial structuring that are not singularly different from those shown by sexually reproducing plants or animals. Microsite‐dependent, divergent selection can maintain high local and regional genetic diversity in microbial populations despite extensive clonality.     

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.     

Clinal variation in MHC diversity with temperature: evidence for the role of host-pathogen interaction on local adaptation in Atlantic salmon

In vertebrates, variability at genes of the Major Histocompatibility Complex (MHC) represents an important adaptation for pathogen resistance, whereby high allelic diversity confers resistance to a greater number of pathogens. Pathogens can maintain diversifying selection pressure on their host's immune system that can vary in intensity based on pathogen richness, pathogen virulence, and length of the cohabitation period, which tend to increase with temperature. In this study, we tested the hypothesis that genetic diversity of MHC increases with temperature along a latitudinal gradient in response to pathogen selective pressure in the wild. A total of 1549 Atlantic salmon from 34 rivers were sampled between 46 degrees N and 58 degrees N in Eastern Canada. The results supported our working hypothesis. In contrast to the overall pattern observed at microsatellites, MHC class II allelic diversity increased with temperature, thus creating a latitudinal gradient. The observed temperature gradient was more pronounced for MHC amino acids of the peptide-binding region (PBR), a region that specifically binds to pathogens, than for the non-PBR. For the subset of rivers analyzed for bacterial diversity, MHC amino acid diversity of the PBR also increased significantly with bacterial diversity in each river. A comparison of the relative influence of temperature and bacterial diversity revealed that the latter could have a predominant role on MHC PBR variability. However, temperature was also identified as an important selective agent maintaining MHC diversity in the wild. Based on the bacteria results and given the putative role of temperature in shaping large-scale patterns of pathogen diversity and virulence, bacterial diversity is a plausible selection mechanism explaining the observed association between temperature and MHC variability. Therefore, we propose that genetic diversity at MHC class II represents local adaptation to cope with pathogen diversity in rivers associated with different thermal regimes. This study illuminates the link between selection pressure from the environment, host immune adaptation, and the large-scale genetic population structure for a nonmodel vertebrate in the wild.