Adaptive tolerance to a pathogenic fungus drives major histocompatibility complex evolution in natural amphibian populations

Amphibians have been affected globally by the disease chytridiomycosis, caused by the fungus Batrachochytrium dendrobatidis (Bd), and we are just now beginning to understand how immunogenetic variability contributes to disease susceptibility. Lineages of an expressed major histocompatibility complex (MHC) class II locus involved in acquired immunity are associated with chytridiomycosis susceptibility in controlled laboratory challenge assays. Here, we extend these findings to natural populations that vary both in exposure and response to Bd. We find that MHC alleles and supertypes associated with Bd survival in the field show a molecular signal of positive selection, while those associated with susceptibility do not, supporting the hypothesis that heritable Bd tolerance is rapidly evolving. We compare MHC supertypes to neutral loci to demonstrate where selection versus demography is shaping MHC variability. One population with Bd tolerance in nature shows a significant signal of directional selection for the same allele (allele Q) that was significantly associated with survival in an earlier laboratory study. Our findings indicate that selective pressure for Bd survival drives rapid immunogenetic adaptation in some natural populations, despite differences in environment and demography. Our field-based analysis of immunogenetic variation confirms that natural amphibian populations have the evolutionary potential to adapt to chytridiomycosis.     

Lost but not forgotten: MHC genotypes predict overwinter survival despite depauperate MHC diversity in a declining frog

The amphibian disease chytridiomycosis, caused by the fungus Batrachochytrium dendrobatidis (Bd), has contributed to the decline of Chiricahua leopard frogs (Rana chiricahuensis), a federally threatened species native to the Southwestern United States. We characterized immunogenetic variability in R. chiricahuensis by sequencing an expressed Major Histocompatibility Complex (MHC) class IIβ gene across 13 natural populations in Arizona, USA, as well as 283 individuals that were captive reared from two egg masses. We recovered a total of five class IIβ MHC alleles compared to 84 alleles previously characterized in eight natural populations of the Arizona congener R. yavapaiensis, demonstrating reduced MHC diversity in R. chiricahuensis. One allele was fixed in five populations but none of the R. chiricahuensis alleles were closely related to R. yavapaiensis allele Q, which is significantly associated with chytridiomycosis resistance in laboratory trials. Nine of 13 R. chiricahuensis population localities were Bd positive, and bearing allele RachDRB*04 was the best genetic predictor of an individual being infected with Bd. A total of three class IIβ alleles were recovered from captive reared individuals, which were released to two natural population localities followed by recapture surveys to assess MHC-based survival over winter, the time when chytridiomycosis outbreaks are most severe. At one site, all released animals were fixed for a single allele and MHC-based survival could not be assessed. At the second site, fewer than half of the released but all of the recaptured individuals were homozygous for RachDRB*05, indicating that MHC genotype is important in determining Bd survival under natural field conditions. We conclude that the limited MHC variation in R. chiricahuensis is likely the consequence rather than the cause of natural selection favoring alleles that promote survival in the face of Bd. Our study highlights that preserving even low levels of functional genetic variation may be essential for population persistence, and that local disease adaptation may present as a reduction in genetic diversity. These finding also suggest that for populations that have declined due to a specific infectious pathogen, MHC-based genetically-informed reintroduction approaches may enhance species recovery efforts.     

Microsatellite and major histocompatibility complex variation in an endangered rattlesnake,the Eastern Massasauga (Sistrurus catenatus)

Genetic diversity is fundamental to maintaining the long‐term viability of populations, yet reduced genetic variation is often associated with small, isolated populations. To examine the relationship between demography and genetic variation, variation at hypervariable loci (e.g., microsatellite DNA loci) is often measured. However, these loci are selectively neutral (or near neutral) and may not accurately reflect genomewide variation. Variation at functional trait loci, such as the major histocompatibility complex (MHC), can provide a better assessment of adaptive genetic variation in fragmented populations. We compared patterns of microsatellite and MHC variation across three Eastern Massasauga (Sistrurus catenatus) populations representing a gradient of demographic histories to assess the relative roles of natural selection and genetic drift. Using 454 deep amplicon sequencing, we identified 24 putatively functional MHC IIB exon 2 alleles belonging to a minimum of six loci. Analysis of synonymous and nonsynonymous substitution rates provided evidence of historical positive selection at the nucleotide level, and Tajima's D provided support for balancing selection in each population. As predicted, estimates of microsatellite allelic richness, observed, heterozygosity, and expected heterozygosity varied among populations in a pattern qualitatively consistent with demographic history and abundance. While MHC allelic richness at the population and individual levels revealed similar trends, MHC nucleotide diversity was unexpectedly high in the smallest population. Overall, these results suggest that genetic variation in the Eastern Massasauga populations in Illinois has been shaped by multiple evolutionary mechanisms. Thus, conservation efforts should consider both neutral and functional genetic variation when managing captive and wild Eastern Massasauga populations.     

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.     

Patterns of selection and allele diversity of class I and class II major histocompatibility loci across the species range of sockeye salmon (Oncorhynchus nerka)

The major histocompatibility complex (MHC), an important component of the vertebrate immune system, provides an important suite of genes to examine the role of genetic diversity at non‐neutral loci for population persistence. We contrasted patterns of diversity at the two classical MHC loci in sockeye salmon (Oncorhynchus nerka), MHC class I (UBA) and MHC class II (DAB), and neutral microsatellite loci across 70 populations spanning the species range from Washington State to Japan. There was no correlation in allelic richness or heterozygosity between MHC loci or between MHC loci and microsatellites. The two unlinked MHC loci may be responding to different selective pressures; the distribution of F_ST values for the two loci was uncorrelated, and evidence for both balancing and directional selection on alleles and lineages of DAB and UBA was observed in populations throughout the species range but rarely on both loci within a population. These results suggest that fluctuating selection has resulted in the divergence of MHC loci in contemporary populations.     

Does Genetic Diversity Predict Health in Humans?

Genetic diversity, especially at genes important for immune functioning within the Major Histocompatibility Complex (MHC), has been associated with fitness-related traits, including disease resistance, in many species. Recently, genetic diversity has been associated with mate preferences in humans. Here we asked whether these preferences are adaptive in terms of obtaining healthier mates. We investigated whether genetic diversity (heterozygosity and standardized mean d²) at MHC and nonMHC microsatellite loci, predicted health in 153 individuals. Individuals with greater allelic diversity (d²) at nonMHC loci and at one MHC locus, linked to HLA-DRB1, reported fewer symptoms over a four-month period than individuals with lower d². In contrast, there were no associations between MHC or nonMHC heterozygosity and health. NonMHC-d² has previously been found to predict male preferences for female faces. Thus, the current findings suggest that nonMHC diversity may play a role in both natural and sexual selection acting on human populations.     

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.     

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.     

Genetic dissimilarity,genetic diversity,and mate preferences in humans

It is clear that genes at the major histocompatibility complex (MHC) are involved in mate preferences in a range of species, including humans. However, many questions remain regarding the MHC's exact influence on mate preference in humans. Some research suggests that genetic dissimilarity and individual genetic diversity (heterozygosity) at the MHC influence mate preferences, but the evidence is often inconsistent across studies. In addition, it is not known whether apparent preferences for MHC dissimilarity are specific to the MHC or reflect a more general preference for genome-wide dissimilarity, and whether MHC-related preferences are dependent on the context of mate choice (e.g., when choosing a short-term and long-term partner). Here, we investigated whether preferences for genetic dissimilarity are specific to the MHC and also whether preferences for genetic dissimilarity and diversity are context dependent. Genetic dissimilarity (number of alleles shared) influenced male, but not female, partner preferences, with males showing a preference for the faces of MHC-dissimilar females in both mating contexts. Genetic diversity [heterozygosity (H) and standardized mean (d²)] influenced both male and female preferences, regardless of mating context. Females preferred males with greater diversity at MHC loci (H) and males preferred females with greater diversity at non-MHC loci (d²) in both contexts. Importantly, these findings provide further support for a special role of the MHC in human sexual selection and suggest that male and female mate preferences may work together to potentially enhance both male and female reproductive success by increasing genetic diversity in offspring.     

High MHC DQB Variation and Asymmetric Allelic Distribution in the Endangered Yangtze Finless Porpoise, Neophocaena phocaenoides asiaeorientalis

The endangered Yangtze finless porpoise is found in the middle and lower reaches of the Yangtze River and its adjoining big lakes. To explore the major histocompatibility complex (MHC) genetic diversity and allelic distribution patterns across its range, we investigated variation at DQB exon 2. From 76 porpoises, we identified 18 DQB sequences. The freshwater Yangtze populations had much higher allelic diversity than marine populations. Among these freshwater populations, the middle-reach population had higher allelic diversity than the lower-reach population. The high DQB diversity level, relative to that of a neutral mtDNA locus, suggests that balancing selection is acting at the DQB gene and that rapid evolution and local positive selection play critical roles in generating and retaining high MHC diversity in the freshwater population. As the balancing selection might be driven by environmental pathogens, we suggest that maintaining MHC variation should be a high priority in the conservation and management of this endangered population, especially as an ex situ conservation strategy.     

Maintaining functional major histocompatibility complex diversity under inbreeding: the case of a selfing vertebrate

Major histocompatibility complex (MHC) genes encode proteins that present pathogen-derived antigens to T-cells, initiating the adaptive immune response in vertebrates. Although populations with low MHC diversity tend to be more susceptible to pathogens, some bottlenecked populations persist and even increase in numbers despite low MHC diversity. Thus, the relative importance of MHC diversity versus genome-wide variability for the long-term viability of populations after bottlenecks and/or under high inbreeding is controversial. We tested the hypothesis that genome-wide inbreeding (estimated using microsatellites) should be more critical than MHC diversity alone in determining pathogen resistance in the self-fertilizing fish Kryptolebias marmoratus by analysing MHC diversity and parasite loads in natural and laboratory populations with different degrees of inbreeding. Both MHC and neutral diversities were lost after several generations of selfing, but we also found evidence of parasite selection acting on MHC diversity and of non-random loss of alleles, suggesting a possible selective advantage of those individuals with functionally divergent MHC, in accordance with the hypothesis of divergent allele advantage. Moreover, we found that parasite loads were better explained by including MHC diversity in the model than by genome-wide (microsatellites) heterozygosity alone. Our results suggest that immune-related overdominance could be the key in maintaining variables rates of selfing and outcrossing in K. marmoratus and other mixed-mating species.     

Genetic characterization of chytrids isolated from larval amphibians collected in central and east Texas

Chytridiomycosis, an emerging infectious disease caused by the fungal pathogen Batrachochytrium dendrobatidis (Bd), has caused amphibian population declines worldwide. Bd was first described in the 1990s and there are still geographic gaps in the genetic analysis of this globally distributed pathogen. Relatively few genetic studies have focused on regions where Bd exhibits low virulence, potentially creating a bias in our current knowledge of the pathogen's genetic diversity. Disease-associated declines have not been recorded in Texas (USA), yet Bd has been detected on amphibians in the state. These strains have not been isolated and characterized genetically; therefore, we isolated, cultured, and genotyped Bd from central Texas and compared isolates to a panel of previously genotyped strains distributed across the Western Hemisphere. We also isolated other chytrids from east Texas not known to infect amphibians. To identify larval amphibian hosts, we sequenced part of the COI gene. Among 37 Bd isolates from Texas, we detected 19 unique multi-locus genotypes, but found no genetic structure associated with host species, Texas localities, or across North America. Isolates from central Texas exhibit high diversity and genetically cluster with BdGPL isolates from the western U.S. that have caused amphibian population declines. This study genetically characterizes isolates of Bd from the south central U.S. and adds to the global knowledge of Bd genotypes.     

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.     

Chromosomal Copy Number Variation,Selection and Uneven Rates of Recombination Reveal Cryptic Genome Diversity Linked to Pathogenicity

Pathogenic fungi constitute a growing threat to both plant and animal species on a global scale. Despite a clonal mode of reproduction dominating the population genetic structure of many fungi, putatively asexual species are known to adapt rapidly when confronted by efforts to control their growth and transmission. However, the mechanisms by which adaptive diversity is generated across a clonal background are often poorly understood. We sequenced a global panel of the emergent amphibian pathogen, Batrachochytrium dendrobatidis (Bd), to high depth and characterized rapidly changing features of its genome that we believe hold the key to the worldwide success of this organism. Our analyses show three processes that contribute to the generation of de novo diversity. Firstly, we show that the majority of wild isolates manifest chromosomal copy number variation that changes over short timescales. Secondly, we show that cryptic recombination occurs within all lineages of Bd, leading to large regions of the genome being in linkage equilibrium, and is preferentially associated with classes of genes of known importance for virulence in other pathosystems. Finally, we show that these classes of genes are under directional selection, and that this has predominantly targeted the Global Panzootic Lineage (BdGPL). Our analyses show that Bd manifests an unusually dynamic genome that may have been shaped by its association with the amphibian host. The rates of variation that we document likely explain the high levels of phenotypic variability that have been reported for Bd, and suggests that the dynamic genome of this pathogen has contributed to its success across multiple biomes and host-species.     

MHC-mediated local adaptation in reciprocally translocated Chinook salmon

Most Pacific salmonid populations have faced significant population declines over the past 30 years. In order to effectively conserve and manage these populations, knowledge of the evolutionary adaptive state of individuals and the scale of adaptation across populations is needed. The vertebrate major histocompatibility complex (MHC) represents an important adaptation to parasites, and genes encoding for the MHC are widely held to be undergoing balancing selection. However, the generality of balancing selection across populations at MHC loci is not well documented. Using Chinook salmon (Oncorhynchus tshawytscha) from two populations, we follow the survival of full-sib family replicates reared in their natal river and reciprocally transplanted to a foreign river to examine selection and local adaptation at the MHC class I and II loci. In both populations, we found evidence of a survivorship advantage associated with nucleotide diversity at the MHC class I locus. In contrast, we found evidence that MHC class II diversity was disadvantageous in one population. There was no evidence that these effects occurred in translocated families, suggesting some degree of local adaptation at the MHC loci. Thus, our results implicate balancing selection at the MHC class I but potentially differing selection across populations at the class II locus.     

Selection and genetic drift in captive versus wild populations: an assessment of neutral and adaptive (MHC-linked) genetic variation in wild and hatchery brown trout (<Emphasis Type="Italic">Salmo trutta</Emphasis>) populations

Captive bred individuals are often released into natural environments to supplement resident populations. Captive bred salmonid fishes often exhibit lower survival rates than their wild brethren and stocking measures may have a negative influence on the overall fitness of natural populations. Stocked fish often stem from a different evolutionary lineage than the resident population and thus may be maladapted for life in the wild, but this phenomenon has also been linked to genetic changes that occur in captivity. In addition to overall loss of genetic diversity via captive breeding, adaptation to captivity has become a major concern. Altered selection pressure in captivity may favour alleles at adaptive loci like the Major Histocompatibility Complex (MHC) that are maladaptive in natural environments. We investigated neutral and MHC-linked genetic variation in three autochthonous and three hatchery populations of Austrian brown trout (Salmo trutta). We confirm a positive selection pressure acting on the MHC II β locus, whereby the signal for positive selection was stronger in hatchery versus wild populations. Additionally, diversity at the MHC II β locus was higher, and more uniform among hatchery samples compared to wild populations, despite equal levels of diversity at neutral loci. We postulate that this stems from a combination of stronger genetic drift and a weakening of positive selection at this locus in wild populations that already have well adapted alleles for their specific environments.     

Evidence for Directional Selection at a Novel Major Histocompatibility Class I Marker in Wild Common Frogs (Rana temporaria) Exposed to a Viral Pathogen (Ranavirus)

Whilst the Major Histocompatibility Complex (MHC) is well characterized in the anuran Xenopus, this region has not previously been studied in another popular model species, the common frog (Rana temporaria). Nor, to date, have there been any studies of MHC in wild amphibian host-pathogen systems. We characterise an MHC class I locus in the common frog, and present primers to amplify both the whole region, and specifically the antigen binding region. As no more than two expressed haplotypes were found in over 400 clones from 66 individuals, it is likely that there is a single class I locus in this species. This finding is consistent with the single class I locus in Xenopus, but contrasts with the multiple loci identified in axolotls, providing evidence that the diversification of MHC class I into multiple loci likely occurred after the Caudata/Anura divergence (approximately 350 million years ago) but before the Ranidae/Pipidae divergence (approximately 230 mya). We use this locus to compare wild populations of common frogs that have been infected with a viral pathogen (Ranavirus) with those that have no history of infection. We demonstrate that certain MHC supertypes are associated with infection status (even after accounting for shared ancestry), and that the diseased populations have more similar supertype frequencies (lower F_ST) than the uninfected. These patterns were not seen in a suite of putatively neutral microsatellite loci. We interpret this pattern at the MHC locus to indicate that the disease has imposed selection for particular haplotypes, and hence that common frogs may be adapting to the presence of Ranavirus, which currently kills tens of thousands of amphibians in the UK each year.     

Is MHC diversity a better marker for conservation than neutral genetic diversity? A case study of two contrasting dolphin populations

Genetic diversity is essential for populations to adapt to changing environments. Measures of genetic diversity are often based on selectively neutral markers, such as microsatellites. Genetic diversity to guide conservation management, however, is better reflected by adaptive markers, including genes of the major histocompatibility complex (MHC). Our aim was to assess MHC and neutral genetic diversity in two contrasting bottlenose dolphin (Tursiops aduncus) populations in Western Australia—one apparently viable population with high reproductive output (Shark Bay) and one with lower reproductive output that was forecast to decline (Bunbury). We assessed genetic variation in the two populations by sequencing the MHC class II DQB, which encompasses the functionally important peptide binding regions (PBR). Neutral genetic diversity was assessed by genotyping twenty‐three microsatellite loci. We confirmed that MHC is an adaptive marker in both populations. Overall, the Shark Bay population exhibited greater MHC diversity than the Bunbury population—for example, it displayed greater MHC nucleotide diversity. In contrast, the difference in microsatellite diversity between the two populations was comparatively low. Our findings are consistent with the hypothesis that viable populations typically display greater genetic diversity than less viable populations. The results also suggest that MHC variation is more closely associated with population viability than neutral genetic variation. Although the inferences from our findings are limited, because we only compared two populations, our results add to a growing number of studies that highlight the usefulness of MHC as a potentially suitable genetic marker for animal conservation. The Shark Bay population, which carries greater adaptive genetic diversity than the Bunbury population, is thus likely more robust to natural or human‐induced changes to the coastal ecosystem it inhabits.     

Selection from parasites favours immunogenetic diversity but not divergence among locally adapted host populations

The unprecedented polymorphism in the major histocompatibility complex (MHC) genes is thought to be maintained by balancing selection from parasites. However, do parasites also drive divergence at MHC loci between host populations, or do the effects of balancing selection maintain similarities among populations? We examined MHC variation in populations of the livebearing fish Poecilia mexicana and characterized their parasite communities. Poecilia mexicana populations in the Cueva del Azufre system are locally adapted to darkness and the presence of toxic hydrogen sulphide, representing highly divergent ecotypes or incipient species. Parasite communities differed significantly across populations, and populations with higher parasite loads had higher levels of diversity at class II MHC genes. However, despite different parasite communities, marked divergence in adaptive traits and in neutral genetic markers, we found MHC alleles to be remarkably similar among host populations. Our findings indicate that balancing selection from parasites maintains immunogenetic diversity of hosts, but this process does not promote MHC divergence in this system. On the contrary, we suggest that balancing selection on immunogenetic loci may outweigh divergent selection causing divergence, thereby hindering host divergence and speciation. Our findings support the hypothesis that balancing selection maintains MHC similarities among lineages during and after speciation (trans‐species evolution).