Natural selection on MHC IIβ in parapatric lake and stream stickleback: Balancing,divergent, both or neither?

Major histocompatibility complex (MHC) genes encode proteins that play a central role in vertebrates' adaptive immunity to parasites. MHC loci are among the most polymorphic in vertebrates' genomes, inspiring many studies to identify evolutionary processes driving MHC polymorphism within populations and divergence between populations. Leading hypotheses include balancing selection favouring rare alleles within populations, and spatially divergent selection. These hypotheses do not always produce diagnosably distinct predictions, causing many studies of MHC to yield inconsistent or ambiguous results. We suggest a novel strategy to distinguish balancing vs. divergent selection on MHC, taking advantage of natural admixture between parapatric populations. With divergent selection, individuals with immigrant alleles will be more infected and less fit because they are susceptible to novel parasites in their new habitat. With balancing selection, individuals with locally rare immigrant alleles will be more fit (less infected). We tested these contrasting predictions using three‐spine stickleback from three replicate pairs of parapatric lake and stream habitats. We found numerous positive and negative associations between particular MHC IIβ alleles and particular parasite taxa. A few allele–parasite comparisons supported balancing selection, and others supported divergent selection between habitats. But, there was no overall tendency for fish with immigrant MHC alleles to be more or less heavily infected. Instead, locally rare MHC alleles (not necessarily immigrants) were associated with heavier infections. Our results illustrate the complex relationship between MHC IIβ allelic variation and spatially varying multispecies parasite communities: different hypotheses may be concurrently true for different allele–parasite combinations.     

Spatio‐temporal variation in parasite communities maintains diversity at the major histocompatibility complex class IIβ in the endangered Rio Grande silvery minnow

Climate change will strongly impact aquatic ecosystems particularly in arid and semi‐arid regions. Fish–parasite interactions will also be affected by predicted altered flow and temperature regimes, and other environmental stressors. Hence, identifying environmental and genetic factors associated with maintaining diversity at immune genes is critical for understanding species’ adaptive capacity. Here, we combine genetic (MHC class IIβ and microsatellites), parasitological and ecological data to explore the relationship between these factors in the remnant wild Rio Grande silvery minnow (Hybognathus amarus) population, an endangered species found in the southwestern United States. Infections with multiple parasites on the gills were observed and there was spatio‐temporal variation in parasite communities and patterns of infection among individuals. Despite its highly endangered status and chronically low genetic effective size, Rio Grande silvery minnow had high allelic diversity at MHC class IIβ with more alleles recognized at the presumptive DAB1 locus compared to the DAB3 locus. We identified significant associations between specific parasites and MHC alleles against a backdrop of generalist parasite prevalence. We also found that individuals with higher individual neutral heterozygosity and higher amino acid divergence between MHC alleles had lower parasite abundance and diversity. Taken together, these results suggest a role for fluctuating selection imposed by spatio‐temporal variation in pathogen communities and divergent allele advantage in maintenance of high MHC polymorphism. Understanding the complex interaction of habitat, pathogens and immunity in protected species will require integrated experimental, genetic and field studies.     

Major histocompatibility complex class II DAB alleles associated with intestinal parasite load in the vulnerable Chinese egret (Egretta eulophotes)

The maintenance of major histocompatibility complex (MHC) polymorphism has been hypothesized to result from many mechanisms such as rare‐allele advantage, heterozygote advantage, and allele counting. In the study reported herein, 224 vulnerable Chinese egrets (Egretta eulophotes) were used to examine these hypotheses as empirical results derived from bird studies are rare. Parasite survey showed that 147 (65.63%) individuals were infected with 1–3 helminths, and 82.31% of these infected individuals carried Ascaridia sp. Using asymmetric polymerase chain reaction technique, 10 DAB1, twelve DAB2, and three DAB3 exon 2 alleles were identified at each single locus. A significant association of the rare allele Egeu‐DAB2*05 (allele frequency: 0.022) with helminth resistance was found for all helminths, as well as for the most abundant morphotype Ascaridia sp. in the separate analyses. Egeu‐DAB2*05 occurred frequently in uninfected individuals, and individuals carrying Egeu‐DAB2*05 had significantly lower helminth morphotypes per individual (HMI) (the number of HMI) and the fecal egg count values. Further, the parasite infection measurements were consistently lower in individuals with an intermediate number of different alleles in the duplicated DAB loci. Significantly, heterozygosity within each DAB locus was not correlated with any parasite infection measurements. These results indicate that the diversity in MHC Egeu‐DAB gene is associated with intestinal parasite load and maintained by pathogen‐driven selection that probably operate through both the rare‐allele advantage and the allele counting strategy, and suggest that Egeu‐DAB2*05 might be a valuable indicator of better resistance to helminth diseases in the vulnerable Chinese egret.     

MHC‐I provides both quantitative resistance and susceptibility to blood parasites in blue tits in the wild

Major histocompatibility complex (MHC) genes are central for the adaptive immune response against parasites. Here, we investigated potential associations among MHC‐I alleles and blood parasite infections in a natural breeding population of a passerine bird, the blue tit Cyanistes caeruleus, in central Spain. We screened both infection status (presence/absence of infection) and infection intensity to the pathogenic blood parasites Haemoproteus and Leucocytozoon. Three MHC‐I alleles (UA104, UA108 and UA117) were associated with higher or lower infection intensities by Leucocytozoon. Interestingly, these associations were dependent on age and were found both among young and adult birds. No MHC alleles were associated with infection intensity by Haemoproteus parasites. In addition, no significant relationships were detected between infection status by Haemoproteus and Leucocytozoon infections and MHC alleles. The very high prevalence of these two parasites in our study population (79–100%) poses challenges to identify associations with infection status and also suggests that clearance of infections may be rare. In conclusion, associations between specific MHC‐I alleles and Leucocytozoon parasites were related to either high or low infection intensities, and hence increased susceptibility or resistance to infection.     

Shared evolutionary origin of major histocompatibility complex polymorphism in sympatric lemurs

Genes of the major histocompatibility complex (MHC) play a central role in adaptive immune responses of vertebrates. They exhibit remarkable polymorphism, often crossing species boundaries with similar alleles or allelic motifs shared across species. This pattern may reflect parallel parasite‐mediated selective pressures, either favouring the long maintenance of ancestral MHC allelic lineages across successive speciation events by balancing selection (“trans‐species polymorphism”), or alternatively favouring the independent emergence of functionally similar alleles post‐speciation via convergent evolution. Here, we investigate the origins of MHC similarity across several species of dwarf and mouse lemurs (Cheirogaleidae). We examined MHC class II variation in two highly polymorphic loci (DRB, DQB) and evaluated the overlap of gut–parasite communities in four sympatric lemurs. We tested for parasite‐MHC associations across species to determine whether similar parasite pressures may select for similar MHC alleles in different species. Next, we integrated our MHC data with those previously obtained from other Cheirogaleidae to investigate the relative contribution of convergent evolution and co‐ancestry to shared MHC polymorphism by contrasting patterns of codon usage at functional vs. neutral sites. Our results indicate that parasites shared across species may select for functionally similar MHC alleles, implying that the dynamics of MHC‐parasite co‐evolution should be envisaged at the community level. We further show that balancing selection maintaining trans‐species polymorphism, rather than convergent evolution, is the primary mechanism explaining shared MHC sequence motifs between species that diverged up to 30 million years ago.     

Blood parasites shape extreme major histocompatibility complex diversity in a migratory passerine

Pathogens are one of the main forces driving the evolution and maintenance of the highly polymorphic genes of the vertebrate major histocompatibility complex (MHC). Although MHC proteins are crucial in pathogen recognition, it is still poorly understood how pathogen‐mediated selection promotes and maintains MHC diversity, and especially so in host species with highly duplicated MHC genes. Sedge warblers (Acrocephalus schoenobaenus) have highly duplicated MHC genes, and using data from high‐throughput MHC genotyping, we were able to investigate to what extent avian malaria parasites explain temporal MHC class I supertype fluctuations in a long‐term study population. We investigated infection status and infection intensities of two different strains of Haemoproteus, that is avian malaria parasites that are known to have significant fitness consequences in sedge warblers. We found that prevalence of avian malaria in carriers of specific MHC class I supertypes was a significant predictor of their frequency changes between years. This finding suggests that avian malaria infections partly drive the temporal fluctuations of the MHC class I supertypes. Furthermore, we found that individuals with a large number of different supertypes had higher resistance to avian malaria, but there was no evidence for an optimal MHC class I diversity. Thus, the two studied malaria parasite strains appear to select for a high MHC class I supertype diversity. Such selection may explain the maintenance of the extremely high number of MHC class I gene copies in sedge warblers and possibly also in other passerines where avian malaria is a common disease.     

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.     

Neutral and selective processes shape MHC gene diversity and expression in stocked brook charr populations (Salvelinus fontinalis)

The capacity of an individual to battle infection is an important fitness determinant in wild vertebrate populations. The major histocompatibility complex (MHC) genes are crucial for a host's adaptive immune system to detect pathogens. However, anthropogenic activities may disrupt natural cycles of co‐evolution between hosts and pathogens. In this study, we investigated the dynamic sequence and expression variation of host parasite interactions in brook charr (Salvelinus fontinalis) in a context of past human disturbance via population supplementation from domestic individuals. To do so, we developed a new method to examine selection shaping MHC diversity within and between populations and found a complex interplay between neutral and selective processes that varied between lakes that were investigated. We provided evidence for a lower introgression rate of domestic alleles and found that parasite infection increased with domestic genomic background of individuals. We also documented an association between individual MHC alleles and parasite taxa. Finally, longer cis‐regulatory minisatellites were positively correlated with MHC II down‐regulation and domestic admixture, suggesting that inadvertent selection during domestication resulted in a lower immune response capacity, through a trade‐off between growth and immunity, which explained the negative selection of domestic alleles at least under certain circumstances.     

Maintaining microendemic primate species along an environmental gradient – parasites as drivers for species differentiation

Understanding the drivers of species adaptations to changing environments on the one hand and the limits for hybridization on the other hand is among the hottest questions in evolutionary biology. Parasites represent one of the major selective forces driving host evolution and at least those with free‐living stages are at the same time dependent on the ecological conditions of their host's habitat. Local immunological adaptations of host species to varying parasite pressure are therefore expected and might represent the genetic basis for ecological speciation and the maintenance of recently diverged species. Madagascar provides one of the rare examples where two partially sympatric primate species (Microcebus griseorufus, M. murinus) and their hybrids, as well as an allopatric species (M. cf rufus) live in close proximity along a very steep environmental gradient ranging from southern dry spiny bush to gallery forest to evergreen eastern humid rain forest, thus mimicking the situation encountered during extensions and retreats of vegetation formations under changing climatic conditions. This system was used to study parasite infection and immune gene (MHC) adaptations to varying parasite pressure that might provide selective advantages to pure species over hybrids. Parasite burdens increased with increasing humidity. M. griseorufus, M. murinus, and their hybrids but not M. rufus shared the same MHC alleles, indicating either retention of ancestral polymorphism or recent gene flow. The hybrids had much higher prevalence of intestinal parasites than either of the parent species living under identical environmental conditions. The different representation of parasites can indicate a handicap for hybrids that maintains species identities.     

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.     

Sex and hatching order modulate the association between MHC‐II diversity and fitness in early‐life stages of a wild seabird

Genes of the major histocompatibility complex (MHC) play a pivotal role in parasite resistance, and their allelic diversity has been associated with fitness variations in several taxa. However, studies report inconsistencies in the direction of this association, with either positive, quadratic or no association being described. These discrepancies may arise because the fitness costs and benefits of MHC diversity differ among individuals depending on their exposure and immune responses to parasites. Here, we investigated in black‐legged kittiwake (Rissa tridactyla) chicks whether associations between MHC class‐II diversity and fitness vary with sex and hatching order. MHC‐II diversity was positively associated with growth and tick clearance in female chicks, but not in male chicks. Our data also revealed a positive association between MHC‐II diversity and survival in second‐hatched female chicks (two eggs being the typical clutch size). These findings may result from condition‐dependent parasite infections differentially impacting sexes in relation to hatching order. We thus suggest that it may be important to account for individual heterogeneities in traits that potentially exert selective pressures on MHC diversity in order to properly predict MHC–fitness associations.     

MHC,parasites and antler development in red deer: no support for the Hamilton & Zuk hypothesis

The Hamilton‐Zuk hypothesis proposes that the genetic benefits of preferences for elaborated secondary sexual traits have their origins in the arms race between hosts and parasites, which maintains genetic variance in parasite resistance. Infection, in turn, can be reflected in the expression of costly sexual ornaments. However, the link between immune genes, infection and the expression of secondary sexual traits has rarely been investigated. Here, we explored whether the presence and identity of functional variants (supertypes) of the highly polymorphic major histocompatibility complex (MHC), which is responsible for the recognition of parasites, predict the load of lung and gut parasites and antler development in the red deer (Cervus elaphus). While we found MHC supertypes to be associated with infection by a number of parasite species, including debilitating lung nematodes, we did not find support for the Hamilton‐Zuk hypothesis. On the contrary, we found that lung nematode load was positively associated with antler development. We also found that the supertypes that were associated with resistance to certain parasites at the same time cause susceptibility to others. Such trade‐offs may undermine the potential genetic benefits of mate choice for resistant partners.     

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

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

Comparison of 454 pyrosequencing methods for characterizing the major histocompatibility complex of nonmodel species and the advantages of ultra deep coverage

Characterization and population genetic analysis of multilocus genes, such as those found in the major histocompatibility complex (MHC) is challenging in nonmodel vertebrates. The traditional method of extensive cloning and Sanger sequencing is costly and time‐intensive and indirect methods of assessment often underestimate total variation. Here, we explored the suitability of 454 pyrosequencing for characterizing multilocus genes for use in population genetic studies. We compared two sample tagging protocols and two bioinformatic procedures for 454 sequencing through characterization of a 185‐bp fragment of MHC DRB exon 2 in wolverines (Gulo gulo) and further compared the results with those from cloning and Sanger sequencing. We found 10 putative DRB alleles in the 88 individuals screened with between two and four alleles per individual, suggesting amplification of a duplicated DRB gene. In addition to the putative alleles, all individuals possessed an easily identifiable pseudogene. In our system, sequence variants with a frequency below 6% in an individual sample were usually artefacts. However, we found that sample preparation and data processing procedures can greatly affect variant frequencies in addition to the complexity of the multilocus system. Therefore, we recommend determining a per‐amplicon‐variant frequency threshold for each unique system. The extremely deep coverage obtained in our study (approximately 5000×) coupled with the semi‐quantitative nature of pyrosequencing enabled us to assign all putative alleles to the two DRB loci, which is generally not possible using traditional methods. Our method of obtaining locus‐specific MHC genotypes will enhance population genetic analyses and studies on disease susceptibility in nonmodel wildlife species.     

Evolution of MHC class II SLA‐DRB1 locus in the Croatian wild boar (Sus scrofa) implies duplication and weak signals of positive selection

The wild boar is an ancestor of the domestic pig and an important game species with the widest geographical range of all ungulates. Although a large amount of data are available on major histocompatibility complex (MHC) variability in domestic pigs, only a few studies have been performed on wild boars. Due to their crucial role in appropriate immune responses and extreme polymorphism, MHC genes represent some of the best candidates for studying the processes of adaptive evolution. Here, we present the results on the variability and evolution of the entire MHC class II SLA‐DRB1 locus exon 2 in 133 wild boars from Croatia. Using direct sequencing and cloning methods, we identified 20 SLA‐DRB1 alleles, including eight new variants, with notable divergence. In some individuals, we documented functional locus duplication, and SLA‐DRB1*04:10 was identified as the allele involved in the duplication. The expression of a duplicated locus was confirmed by cloning and sequencing cDNA‐derived amplicons. Based on individual genotypes, we were able to assume that alleles SLA‐DRB1*04:10 and SLA‐DRB1*06:07 are linked as an allelic combination that co‐evolves as a two‐locus haplotype. Our investigation of evolutionary processes at the SLA‐DRB1 locus confirmed the role of intralocus recombination in generating allelic variability, whereas tests of positive selection based on the dN/dS (non‐synonymous/synonymous substitution rate ratio) test revealed atypically weak and ambiguous signals.     

Disentangling the role of MHC‐dependent ‘good genes' and ‘compatible genes' in mate‐choice decisions of three‐spined sticklebacks Gasterosteus aculeatus under semi‐natural conditions

To investigate and disentangle the role of major histocompatibility complex (MHC)‐based ‘good genes' and ‘compatible genes' in mate choice, three‐spined sticklebacks Gasterosteus aculeatus with specific MHC IIB genotypes were allowed to reproduce in an outdoor enclosure system. Here, fish were protected from predators but encountered their natural parasites. Mate choice for an intermediate genetic distance between parental MHC genotypes was observed, which would result in intermediate diversity in the offspring, but no mate choice based on good genes was found under the current semi‐natural conditions. Investigation of immunological variables revealed that the less‐specific innate immune system was more active in individuals with a genetically more divergent MHC allele repertoire. This suggests the need to compensate for an MHC‐diminished T‐cell repertoire and potentially explains the observed mate choice for intermediate MHC genetic distance. The present findings support a general pattern of mate choice for intermediate MHC diversity (i.e. compatible genes). In addition, the potentially dynamic role of MHC good genes in mate choice under different parasite pressures is discussed in the light of present and previous results.     

Global warming will reshuffle the areas of high prevalence and richness of three genera of avian blood parasites

The importance of parasitism for host populations depends on local parasite richness and prevalence: usually host individuals face higher infection risk in areas where parasites are most diverse, and host dispersal to or from these areas may have fitness consequences. Knowing how parasites are and will be distributed in space and time (in a context of global change) is thus crucial from both an ecological and a biological conservation perspective. Nevertheless, most research articles focus just on elaborating models of parasite distribution instead of parasite diversity. We produced distribution models of the areas where haemosporidian parasites are currently highly diverse (both at community and at within‐host levels) and prevalent among Iberian populations of a model passerine host: the blackcap Sylvia atricapilla; and how these areas are expected to vary according to three scenarios of climate change. On the basis of these models, we analysed whether variation among populations in parasite richness or prevalence are expected to remain the same or change in the future, thereby reshuffling the geographic mosaic of host‐parasite interactions as we observe it today. Our models predict a rearrangement of areas of high prevalence and richness of parasites in the future, with Haemoproteus and Leucocytozoon parasites (today the most diverse genera in blackcaps) losing areas of high diversity and Plasmodium parasites (the most virulent ones) gaining them. Likewise, the prevalence of multiple infections and parasite infracommunity richness would be reduced. Importantly, differences among populations in the prevalence and richness of parasites are expected to decrease in the future, creating a more homogeneous parasitic landscape. This predicts an altered geographic mosaic of host‐parasite relationships, which will modify the interaction arena in which parasite virulence evolves.     

Association between host's genetic diversity and parasite burden in damselflies

Recent research indicates that low genetic variation in individuals can increase susceptibility to parasite infection, yet evidence from natural invertebrate populations remains scarce. Here, we studied the relationship between genetic heterozygosity, measured as AFLP‐based inbreeding coefficient f_AFLP, and gregarine parasite burden from eleven damselfly, Calopteryx splendens, populations. We found that in the studied populations, 5–92% of males were parasitized by endoparasitic gregarines (Apicomplexa: Actinocephalidae). Number of parasites ranged from none to 47 parasites per male, and parasites were highly aggregated in a few hosts. Mean individual f_AFLP did not differ between populations. Moreover, we found a positive association between individual's inbreeding coefficient and parasite burden. In other words, the more homozygous the individual, the more parasites it harbours. Thus, parasites are likely to pose strong selection pressure against inbreeding and homozygosity. Our results support the heterozygosity‐fitness correlation hypothesis, which suggests the importance of heterozygosity for an individual's pathogen resistance.     

Testing parasite ‘intimacy’: the whipworm Trichuris muris in the European house mouse hybrid zone

Host‐parasite interaction studies across hybrid zones often focus on host genetic variation, treating parasites as homogeneous. ‘Intimately’ associated hosts and parasites might be expected to show similar patterns of genetic structure. In the literature, factors such as no intermediate host and no free‐living stage have been proposed as ‘intimacy’ factors likely constraining parasites to closely follow the evolutionary history of their hosts. To test whether the whipworm, Trichuris muris, is intimately associated with its house mouse host, we studied its population genetics across the European house mouse hybrid zone (HMHZ) which has a strong central barrier to gene flow between mouse taxa. T. muris has a direct life cycle and nonmobile free stage: if these traits constrain the parasite to an intimate association with its host we expect a geographic break in the parasite genetic structure across the HMHZ. We genotyped 205 worms from 56 localities across the HMHZ and additionally T. muris collected from sympatric woodmice (Apodemus spp.) and allopatric murine species, using mt‐COX1, ITS1‐5.8S‐ITS2 rDNA and 10 microsatellites. We show four haplogroups of mt‐COX1 and three clear ITS1‐5.8S‐ITS2 clades in the HMHZ suggesting a complex demographic/phylogeographic history. Microsatellites show strong structure between groups of localities. However, no marker type shows a break across the HMHZ. Whipworms from Apodemus in the HMHZ cluster, and share mitochondrial haplotypes, with those from house mice. We conclude Trichuris should not be regarded as an ‘intimate’ parasite of the house mouse: while its life history might suggest intimacy, passage through alternate hosts is sufficiently common to erase signal of genetic structure associated with any particular host taxon.