Patterns of MHC‐dependent mate selection in humans and nonhuman primates: a meta‐analysis

Genes of the major histocompatibility complex (MHC) in vertebrates are integral for effective adaptive immune response and are associated with sexual selection. Evidence from a range of vertebrates supports MHC‐based preference for diverse and dissimilar mating partners, but evidence from human mate choice studies has been disparate and controversial. Methodologies and sampling peculiarities specific to human studies make it difficult to know whether wide discrepancies in results among human populations are real or artefact. To better understand what processes may affect MHC‐mediated mate choice across humans and nonhuman primates, we performed phylogenetically controlled meta‐analyses using 58 effect sizes from 30 studies across seven primate species. Primates showed a general trend favouring more MHC‐diverse mates, which was statistically significant for humans. In contrast, there was no tendency for MHC‐dissimilar mate choice, and for humans, we observed effect sizes indicating selection of both MHC‐dissimilar and MHC‐similar mates. Focusing on MHC‐similar effect sizes only, we found evidence that preference for MHC similarity was an artefact of population ethnic heterogeneity in observational studies but not among experimental studies with more control over sociocultural biases. This suggests that human assortative mating biases may be responsible for some patterns of MHC‐based mate choice. Additionally, the overall effect sizes of primate MHC‐based mating preferences are relatively weak (Fisher's Z correlation coefficient for dissimilarity Zr = 0.044, diversity Zr = 0.153), calling for careful sampling design in future studies. Overall, our results indicate that preference for more MHC‐diverse mates is significant for humans and likely conserved across primates.     

MHC,mate choice and heterozygote advantage in a wild social primate

Preferences for mates carrying dissimilar genes at the major histocompatibility complex (MHC) may help animals increase offspring pathogen resistance or avoid inbreeding. Such preferences have been reported across a range of vertebrates, but have rarely been investigated in social species other than humans. We investigated mate choice and MHC dynamics in wild baboons (Papio ursinus). MHC Class II DRB genes and 16 microsatellite loci were genotyped across six groups (199 individuals). Based on the survey of a key segment of the gene‐rich MHC, we found no evidence of mate choice for MHC dissimilarity, diversity or rare MHC genotypes. First, MHC dissimilarity did not differ from random expectation either between parents of the same offspring or between immigrant males and females from the same troop. Second, female reproductive success was not influenced by MHC diversity or genotype frequency. Third, population genetic structure analysis revealed equally high genotypic differentiation among troops, and comparable excess heterozygosity within troops for juveniles, at both Mhc‐DRB and neutral loci. Nevertheless, the age structure of Mhc‐DRB heterozygosity suggested higher longevity for heterozygotes, which should favour preferences for MHC dissimilarity. We propose that high levels of within‐group outbreeding, resulting from group‐living and sex‐biased dispersal, might weaken selection for MHC‐disassortative mate choice.     

Explaining global variation in the latitudinal diversity gradient: Meta‐analysis confirms known patterns and uncovers new ones

Aim

The pattern of increasing biological diversity from high latitudes to the equator [latitudinal diversity gradient (LDG)] has been recognized for > 200 years. Empirical studies have documented this pattern across many different organisms and locations. Our goal was to quantify the evidence for the global LDG and the associated spatial, taxonomic and environmental factors. We performed a meta‐analysis on a large number of individual LDGs that have been published in the 14 years since Hillebrand's ground‐breaking meta‐analysis of the LDG, using meta‐analysis and meta‐regression approaches largely new to the fields of ecology and biogeography.

Location

Global.

Time period

January 2003–September 2015.

Major taxa studied

Bacteria, protists, plants, fungi and animals.

Methods

We synthesized the outcomes of 389 individual cases of LDGs from 199 papers published since 2003, using hierarchical mixed‐effects meta‐analysis and multiple meta‐regression. Additionally, we re‐analysed Hillebrand's original dataset using modern methods.

Results

We confirmed the generality of the LDG, but found the pattern to be weaker than was found in Hillebrand's study. We identified previously unreported variation in LDG strength and slope across longitude, with evidence that the LDG is strongest in the Western Hemisphere. Locational characteristics, such as habitat and latitude range, contributed significantly to LDG strength, whereas organismal characteristics, including taxonomic group and trophic level, did not. Modern meta‐analytical models that incorporate hierarchical structure led to more conservative and sometimes contrasting effect size estimates relative to Hillebrand's initial analysis, whereas meta‐regression revealed underlying patterns in Hillebrand's dataset that were not apparent with a traditional analysis.

Main conclusions

We present evidence of global latitudinal, longitudinal and habitat‐based patterns in the LDG, which are apparent across both marine and terrestrial realms and over a broad taxonomic range of organisms, from bacteria to plants and vertebrates.     

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.     

MHC‐disassortative mate choice and inbreeding avoidance in a solitary primate

Sexual selection theory suggests that choice for partners carrying dissimilar genes at the major histocompatibility complex (MHC) may play a role in maintaining genetic variation in animal populations by limiting inbreeding or improving the immunity of future offspring. However, it is often difficult to establish whether the observed MHC dissimilarity among mates drives mate choice or represents a by‐product of inbreeding avoidance based on MHC‐independent cues. Here, we used 454‐sequencing and a 10‐year study of wild grey mouse lemurs (Microcebus murinus), small, solitary primates from western Madagascar, to compare the relative importance on the mate choice of two MHC class II genes, DRB and DQB, that are equally variable but display contrasting patterns of selection at the molecular level, with DRB under stronger diversifying selection. We further assessed the effect of the genetic relatedness and of the spatial distance among candidate mates on the detection of MHC‐dependent mate choice. Our results reveal inbreeding avoidance, along with disassortative mate choice at DRB, but not at DQB. DRB‐disassortative mate choice remains detectable after excluding all related dyads (characterized by a relatedness coefficient r > 0), but varies slightly with the spatial distance among candidate mates. These findings suggest that the observed deviations from random mate choice at MHC are driven by functionally important MHC genes (like DRB) rather than passively resulting from inbreeding avoidance and further emphasize the need for taking into account the spatial and genetic structure of the population in correlative tests of MHC‐dependent mate choice.     

Mate choice for neutral and MHC genetic characteristics in Alpine marmots: different targets in different contexts?

Sexual selection through female mate choice for genetic characteristics has been suggested to be an important evolutionary force maintaining genetic variation in animal populations. However, the genetic targets of female mate choice are not clearly identified and whether female mate choice is based on neutral genetic characteristics or on particular functional loci remains an open question. Here, we investigated the genetic targets of female mate choice in Alpine marmots (Marmota marmota), a socially monogamous mammal where extra‐pair paternity (EPP) occurs. We used 16 microsatellites to describe neutral genetic characteristics and two MHC loci belonging to MHC class I and II as functional genetic characteristics. Our results reveal that (1) neutral and MHC genetic characteristics convey different information in this species, (2) social pairs show a higher MHC class II dissimilarity than expected under random mate choice, and (3) the occurrence of EPP increases when social pairs present a high neutral genetic similarity or dissimilarity but also when they present low MHC class II dissimilarity. Thus, female mate choice is based on both neutral and MHC genetic characteristics, and the genetic characteristics targeted seem to be context dependent (i.e., the genes involved in social mate choice and genetic mate choice differ). We emphasize the need for empirical studies of mate choice in the wild using both neutral and MHC genetic characteristics because whether neutral and functional genetic characteristics convey similar information is not universal.     

Extra‐pair mating in a passerine bird with highly duplicated major histocompatibility complex class II: Preference for the golden mean

Genes of the major histocompatibility complex (MHC) are essential in vertebrate adaptive immunity, and they are highly diverse and duplicated in many lineages. While it is widely established that pathogen‐mediated selection maintains MHC diversity through balancing selection, the role of mate choice in shaping MHC diversity is debated. Here, we investigate female mating preferences for MHC class II (MHCII) in the bluethroat (Luscinia svecica), a passerine bird with high levels of extra‐pair paternity and extremely duplicated MHCII. We genotyped family samples with mixed brood paternity and categorized their MHCII alleles according to their functional properties in peptide binding. Our results strongly indicate that females select extra‐pair males in a nonrandom, self‐matching manner that provides offspring with an allelic repertoire size closer to the population mean, as compared to offspring sired by the social male. This is consistent with a compatible genes model for extra‐pair mate choice where the optimal allelic diversity is intermediate, not maximal. This golden mean presumably reflects a trade‐off between maximizing pathogen recognition benefits and minimizing autoimmunity costs. Our study exemplifies how mate choice can reduce the population variance in individual MHC diversity and exert strong stabilizing selection on the trait. It also supports the hypothesis that extra‐pair mating is adaptive through altered genetic constitution in offspring.     

No evidence for MHC class I‐based disassortative mating in a wild population of great tits

Genes of the major histocompatibility complex (MHC) are regarded as a potentially important target of mate choice due to the fitness benefits that may be conferred to the offspring. According to the complementary genes hypothesis, females mate with MHC dissimilar males to enhance the immunocompetence of their offspring or to avoid inbreeding depression. Here, we investigate whether selection favours a preference for maximally dissimilar or optimally dissimilar MHC class I types, based on MHC genotypes, average amino acid distances and the functional properties of the antigen‐binding sites (MHC supertypes); and whether MHC type dissimilarity predicts relatedness between mates in a wild great tit population. In particular, we explore the role that MHC class I plays in female mate choice decisions while controlling for relatedness and spatial population structure, and examine the reproductive fitness consequences of MHC compatibility between mates. We find no evidence for the hypotheses that females select mates on the basis of either maximal or optimal MHC class I dissimilarity. A weak correlation between MHC supertype sharing and relatedness suggests that MHC dissimilarity at functional variants may not provide an effective index of relatedness. Moreover, the reproductive success of pairs did not vary with MHC dissimilarity. Our results provide no support for the suggestion that selection favours, or that mate choice realizes, a preference for complimentary MHC types.     

Mate choice for major histocompatibility complex genetic divergence as a bet-hedging strategy in the Atlantic salmon (Salmo salar)

Major histocompatibility complex (MHC)-dependent mating preferences have been observed across vertebrate taxa and these preferences are expected to promote offspring disease resistance and ultimately, viability. However, little empirical evidence linking MHC-dependent mate choice and fitness is available, particularly in wild populations. Here, we explore the adaptive potential of previously observed patterns of MHC-dependent mate choice in a wild population of Atlantic salmon (Salmo salar) in Québec, Canada, by examining the relationship between MHC genetic variation and adult reproductive success and offspring survival over 3 years of study. While Atlantic salmon choose their mates in order to increase MHC diversity in offspring, adult reproductive success was in fact maximized between pairs exhibiting an intermediate level of MHC dissimilarity. Moreover, patterns of offspring survival between years 0+ and 1+, and 1+ and 2+ and population genetic structure at the MHC locus relative to microsatellite loci indicate that strong temporal variation in selection is likely to be operating on the MHC. We interpret MHC-dependent mate choice for diversity as a likely bet-hedging strategy that maximizes parental fitness in the face of temporally variable and unpredictable natural selection pressures.     

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.     

Occurrence of extra‐pair paternity is connected to social male's MHC‐variability in the scarlet rosefinch Carpodacus erythrinus

Genes of the Major Histocompatibility Complex (MHC) represent an essential component of the vertebrate acquired immune system. In the last decades, the role of MHC genes in mate choice has been subject of particular scientific interest. However, results of studies dealing with this topic in different species are equivocal and mechanisms conducting MHC‐based mate choice are still puzzling. We investigated the impact of MHC class I variability on within‐pair and extra‐pair fertilisation success in a wild population of a socially monogamous passerine bird with considerable rates of extra‐pair paternity, the scarlet rosefinch Carpodacus erythrinus. We found some support for the ‘good‐genes‐as‐heterozygosity model’, as social males of high MHC‐heterozygosity were cheated by their females less frequently than less MHC‐heterozygous males. However, cuckolding males were not more MHC‐heterozygous than the cheated social males, nor were extra‐pair young more MHC‐heterozygous than within‐pair young. We did not find any evidence for mating preferences according to the complementarity model.     

MHC class II‐assortative mate choice in European badgers (Meles meles)

The major histocompatibility complex (MHC) plays a crucial role in the immune system, and in some species, it is a target by which individuals choose mates to optimize the fitness of their offspring, potentially mediated by olfactory cues. Under the genetic compatibility hypothesis, individuals are predicted to choose mates with compatible MHC alleles, to increase the fitness of their offspring. Studies of MHC‐based mate choice in wild mammals are under‐represented currently, and few investigate more than one class of MHC genes. We investigated mate choice based on the compatibility of MHC class I and II genes in a wild population of European badgers (Meles meles). We also investigated mate choice based on microsatellite‐derived pairwise relatedness, to attempt to distinguish MHC‐specific effects from genomewide effects. We found MHC‐assortative mating, based on MHC class II, but not class I genes. Parent pairs had smaller MHC class II DRB amino acid distances and smaller functional distances than expected from random pairings. When we separated the analyses into within‐group and neighbouring‐group parent pairs, only neighbouring‐group pairs showed MHC‐assortative mating, due to similarity at MHC class II loci. Our randomizations showed no evidence of genomewide‐based inbreeding, based on 35 microsatellite loci; MHC class II similarity was therefore the apparent target of mate choice. We propose that MHC‐assortative mate choice may be a local adaptation to endemic pathogens, and this assortative mate choice may have contributed to the low MHC genetic diversity in this population.     

Sexual selection explains more functional variation in the mammalian major histocompatibility complex than parasitism

Understanding drivers of genetic diversity at the major histocompatibility complex (MHC) is vitally important for predicting how vertebrate immune defence might respond to future selection pressures and for preserving immunogenetic diversity in declining populations. Parasite-mediated selection is believed to be the major selective force generating MHC polymorphism, and while MHC-based mating preferences also exist for multiple species including humans, the general importance of mate choice is debated. To investigate the contributions of parasitism and sexual selection in explaining among-species variation in MHC diversity, we applied comparative methods and meta-analysis across 112 mammal species, including carnivores, bats, primates, rodents and ungulates. We tested whether MHC diversity increased with parasite richness and relative testes size (as an indicator of the potential for mate choice), while controlling for phylogenetic autocorrelation, neutral mutation rate and confounding ecological variables. We found that MHC nucleotide diversity increased with parasite richness for bats and ungulates but decreased with parasite richness for carnivores. By contrast, nucleotide diversity increased with relative testes size for all taxa. This study provides support for both parasite-mediated and sexual selection in shaping functional MHC polymorphism across mammals, and importantly, suggests that sexual selection could have a more general role than previously thought.     

MHC‐dependent survival in a wild population: evidence for hidden genetic benefits gained through extra‐pair fertilizations

Females should prefer to be fertilized by males that increase the genetic quality of their offspring. In vertebrates, genes of the major histocompatibility complex (MHC) play a key role in the acquired immune response and have been shown to affect mating preferences. They are therefore important candidates for the link between mate choice and indirect genetic benefits. Higher MHC diversity may be advantageous because this allows a wider range of pathogens to be detected and combated. Furthermore, individuals harbouring rare MHC alleles might better resist pathogen variants that have evolved to evade common MHC alleles. In the Seychelles warbler, females paired with low MHC‐diversity males elevate the MHC diversity of their offspring to levels comparable to the population mean by gaining extra‐pair fertilizations. Here, we investigate whether increased MHC diversity results in higher life expectancy and whether there are any additional benefits of extra‐pair fertilizations. Our 10‐year study found a positive association between MHC diversity and juvenile survival, but no additional survival advantage of extra‐pair fertilizations. In addition, offspring with a specific allele (Ase‐ua4) had a fivefold longer life expectancy than offspring without this allele. Consequently, the interacting effects of sexual selection and pathogen‐mediated viability selection appear to be important for maintaining MHC variation in the Seychelles warbler. Our study supports the prediction that MHC‐dependent extra‐pair fertilizations result in genetic benefits for offspring in natural populations. However, such genetic benefits might be hidden and not necessarily apparent in the widely used fitness comparison of extra‐ and within‐pair offspring.     

MATE CHOICE FOR NONADDITIVE GENETIC BENEFITS CORRELATE WITH MHC DISSIMILARITY IN THE ROSE BITTERLING (RHODEUS OCELLATUS)

Good genes models of mate choice predict additive genetic benefits of choice whereas the compatibility hypothesis predicts nonadditive fitness benefits. Here the Chinese rose bitterling, Rhodeus ocellatus, a freshwater fish with a resource‐based mating system, was used to separate additive and nonadditive genetic benefits of female mate choice. A sequential blocked mating design was used to test female mate preferences, and a cross‐classified breeding design coupled with in vitro fertilizations for fitness benefits of mate choice. In addition, the offspring produced by the pairing of preferred and nonpreferred males were reared to maturity and their fitness traits were compared. Finally, the MHC DAB1 gene was typed and male MHC genotypes were correlated with female mate choice. Females showed significant mate preferences but preferences were not congruent among females. There was a significant interaction of male and female genotype on offspring survival, rate of development, growth rate, and body size. No significant male additive effects on offspring fitness were observed. Female mate preferences corresponded with male genetic compatibility, which correlated with MHC dissimilarity. It is proposed that in the rose bitterling genetic compatibility is the mechanism by which females obtain a fitness benefit through mate choice and that male MHC dissimilarity, likely mediated by odor cues, indicates genetic compatibility.     

The dilemma of Fisherian sexual selection: Mate choice for indirect benefits despite rarity and overall weakness of trait‐preference genetic correlation

Fisher's mechanism of sexual selection is a fundamental element of evolutionary theory. In it nonrandom mate choice causes a genetic covariance between a male trait and female preference for that trait and thereby generates a positive feedback process sustaining accelerated coevolution of the trait and preference. Numerous theoretical models of Fisher's mechanism have confirmed its mathematical underpinnings, yet biologists have often failed to find evidence for trait‐preference genetic correlation in populations in which the mechanism was expected to function. We undertook a survey of the literature to conduct a formal meta‐analysis probing the incidence and strength of trait‐preference correlation among animal species. Our meta‐analysis found significant positive genetic correlations in fewer than 20% of the species studied and an overall weighted correlation that is slightly positive. Importantly, a significant positive correlation was not found in any thorough study that included multiple subgroups. We discuss several ways in which the dynamic, multivariate nature of mate choice may reduce the trait‐preference genetic correlation predicted by Fisher's mechanism. We then entertain the possibilities that Fisherian‐like processes sometimes function without genetic correlation, and that mate choice may persist in a population as long as genetic correlation, and therefore Fisher's mechanism, occurs intermittently.     

Evaluating the existence and benefit of major histocompatibility complex‐based mate choice in an isolated owl population

How mate preferences evolve in the first place has been a major conundrum for sexual selection. Some hypotheses explaining this assume fitness benefit derived from subsequent generations. Major histocompatibility complex (MHC)‐based mate choice is a representative example of the mate choice that is associated with such trans‐generational mechanisms. To provide evidences for fitness benefit of MHC‐based mate choice, previous studies assessed the association between own MHC genotype and own fitness components. However, the association between MHC‐based mate choice in the parental generation and fitness components in the resultant offspring generation has only rarely been measured in wild populations. Focusing on the isolated population of the monogamous Ryukyu Scops Owl (Otus elegans interpositus) on Minami‐daito Island, Japan, we found evidence of MHC‐based mate choice. However, we found no evidence of MHC‐based mate choice increasing own reproductive success or offspring survival. This is a rare case study that directly examines the existence of the trans‐generational indirect benefit of MHC‐based mate choice for genetic compatibility from trans‐generational data in a wild bird population. By investigating the fitness benefits of mate choice, this study serves to facilitate our understanding of the evolution of MHC‐based mate choice.     

Can MHC‐assortative partner choice promote offspring diversity? A new combination of MHC‐dependent behaviours among sexes in a highly successful invasive mammal

Sexual selection involving genetically disassortative mate choice is one of several evolutionary processes that can maintain or enhance population genetic variability. Examples of reproductive systems in which choosers (generally females) select mates depending on their major histocompatibility complex (MHC) genes have been reported for several vertebrate species. Notably, the role of MHC‐dependent choice not in mating contexts, but in other kinds of social interactions such as in the establishment of complex social systems, has not yet drawn significant scientific interest and is virtually absent from the literature. We have investigated male and female MHC‐dependent choice in an invasive population of North American raccoons (Procyon lotor) in Germany. Both male and female raccoons rely on olfaction for individual recognition. Males have an unusually complex social system in which older individuals choose unrelated younger ones to form stable male coalitions that defend territories and a monopoly over females. We have confirmed that females perform MHC‐disassortative mate choice and that this behaviour fosters genetic diversity of offspring. We have also observed that males build coalitions by choosing male partners depending on their MHC, but in an assortative manner. This is the first observation of antagonistic MHC‐dependent behaviours among sexes. We show that this is the only combination of MHC‐dependent partner choice that leads to outbreeding. In the case of introduced raccoons, such behaviours can act together to promote the invasive potential of the species by increasing its adaptive genetic divergence.     

Major histocompatibility complex variation and evolution at a single, expressed DQA locus in two genera of elephants

Genes of the vertebrate major histocompatibility complex (MHC) are crucial to defense against infectious disease, provide an important measure of functional genetic diversity, and have been implicated in mate choice and kin recognition. As a result, MHC loci have been characterized for a number of vertebrate species, especially mammals; however, elephants are a notable exception. Our study is the first to characterize patterns of genetic diversity and natural selection in the elephant MHC. We did so using DNA sequences from a single, expressed DQA locus in elephants. We characterized six alleles in 30 African elephants (Loxodonta africana) and four alleles in three Asian elephants (Elephas maximus). In addition, for two of the African alleles and three of the Asian alleles, we characterized complete coding sequences (exons 1–5) and nearly complete non-coding sequences (introns 2–4) for the class II DQA loci. Compared to DQA in other wild mammals, we found moderate polymorphism and allelic diversity and similar patterns of selection; patterns of non-synonymous and synonymous substitutions were consistent with balancing selection acting on the peptides involved in antigen binding in the second exon. In addition, balancing selection has led to strong trans-species allelism that has maintained multiple allelic lineages across both genera of extant elephants for at least 6 million years. We discuss our results in the context of MHC diversity in other mammals and patterns of evolution in elephants.     

Ecology can inform genetics: Disassortative mating contributes to MHC polymorphism in Leach’s storm‐petrels (Oceanodroma leucorhoa)

Studies of MHC‐based mate choice in wild populations often test hypotheses on species exhibiting female choice and male–male competition, which reflects the general prevalence of females as the choosy sex in natural systems. Here, we examined mutual mate‐choice patterns in a small burrow‐nesting seabird, the Leach’s storm‐petrel (Oceanodroma leucorhoa), using the major histocompatibility complex (MHC). The life history and ecology of this species are extreme: both partners work together to fledge a single chick during the breeding season, a task that requires regularly travelling hundreds of kilometres to and from foraging grounds over a 6‐ to 8‐week provisioning period. Using a 5‐year data set unprecedented for this species (n = 1078 adults and 925 chicks), we found a positive relationship between variation in the likelihood of female reproductive success and heterozygosity at Ocle‐DAB2, a MHC class IIB locus. Contrary to previous reports rejecting disassortative mating as a mechanism for maintaining genetic polymorphism in this species, here we show that males make significant disassortative mate‐choice decisions. Variability in female reproductive success suggests that the most common homozygous females (Ocle‐DAB2*01/Ocle‐DAB2*01) may be physiologically disadvantaged and, therefore, less preferred as lifelong partners for choosy males. The results from this study support the role of mate choice in maintaining high levels of MHC variability in a wild seabird species and highlight the need to incorporate a broader ecological framework and sufficient sample sizes into studies of MHC‐based mating patterns in wild populations in general.