Major Histocompatibility Complex Heterozygosity Research Articles

No evidence for a role of MHC class II genotype in the chemical encoding of heterozygosity and relatedness in Antarctic fur seals.

Despite decades of research, surprisingly little is known about the mechanism(s) by which an individual's genotype is encoded in odour. Many studies have focused on the role of the major histocompatibility complex (MHC) owing to its importance for survival and mate choice. However, the salience of MHC-mediated odours compared to chemicals influenced by the rest of the genome remains unclear, especially in wild populations where it is challenging to quantify and control for the effects of the genomic background. We addressed this issue in Antarctic fur seals by analysing skin swabs together with full-length MHC DQB II exon 2 sequences and data from 41 genome-wide distributed microsatellites. We did not find any effects of MHC relatedness on chemical similarity and there was also no relationship between MHC heterozygosity and chemical diversity. However, multilocus heterozygosity showed a significant positive association with chemical diversity, even after controlling for MHC heterozygosity. Our results appear to rule out a dominant role of the MHC in the chemical encoding of genetic information in a wild vertebrate population and highlight the need for genome-wide approaches to elucidate the mechanism(s) and specific genes underlying genotype-odour associations.

Does MHC Heterozygosity Promote IgA Plasmablast Diversity in the Gut?

Abstract The diversity of protein antigens the adaptive immune system can respond to is governed by polymorphic major histocompatibility complex (MHC) molecules. Because MHC alleles are co-dominantly expressed, MHC heterozygosity should allow for a wider diversity of antigens to activate T cells. B cells present antigen via MHC molecules to T cells, and through the ensuing T cell interaction, differentiate into plasma cells. Because of this, MHC heterozygosity should result in the generation of a plasma cell pool able to generate antibodies that target a wider array of antigens. To investigate this claim, we compared B cell selection dynamics between homozygote and heterozygote MHC congenic mice within the germinal centers (GCs) of Peyer’s patches; the major secondary lymphoid tissues of the gut where plasma cells develop in response to the microbiota. I have observed differences in the distribution of GC B cells between the dark zone (DZ) and light zone (LZ) of GCs. Specifically, GC B cells in MHC heterozygotes are found in greater abundance in the LZ and lower abundance in the DZ compared the GC B cells from MHC homozygote mice, which suggests that B cells are more capable of interacting with T cells in MHC heterozygotes. MHC heterozygotes also have significantly higher abundance of GC-T FHcells in their Peyer’s patches. I have observed that MHC heterozygote mice show enhanced binding of IgA to SI-resident bacteria. Future experiments seek to sort-purify IgA-bound SI-resident bacteria from MHC heterozygotes and homozygotes for 16S analysis to determine if MHC heterozygotes bind a more diverse array of bacterial species. We will also perform IgH-sequencing to define the effect of MHC heterozygosity on repertoire diversity of plasma cell populations. Supported by grants from the NIH (R21AI142409, R01AII55887)

Intronic primers reveal unexpectedly high major histocompatibility complex diversity in Antarctic fur seals

The major histocompatibility complex (MHC) is a group of genes comprising one of the most important components of the vertebrate immune system. Consequently, there has been much interest in characterising MHC variation and its relationship with fitness in a variety of species. Due to the exceptional polymorphism of MHC genes, careful PCR primer design is crucial for capturing all of the allelic variation present in a given species. We therefore developed intronic primers to amplify the full-length 267 bp protein-coding sequence of the MHC class II DQB exon 2 in the Antarctic fur seal. We then characterised patterns of MHC variation among mother–offspring pairs from two breeding colonies and detected 19 alleles among 771 clone sequences from 56 individuals. The distribution of alleles within and among individuals was consistent with a single-copy, classical DQB locus showing Mendelian inheritance. Amino acid similarity at the MHC was significantly associated with genome-wide relatedness, but no relationship was found between MHC heterozygosity and genome-wide heterozygosity. Finally, allelic diversity was several times higher than reported by a previous study based on partial exon sequences. This difference appears to be related to allele-specific amplification bias, implying that primer design can strongly impact the inference of MHC diversity.

Heterozygosity of the major histocompatibility complex predicts later self-reported pubertal maturation in men

Individual variation in the age of pubertal onset is linked to physical and mental health, yet the factors underlying this variation are poorly understood. Life history theory predicts that individuals at higher risk of mortality due to extrinsic causes such as infectious disease should sexually mature and reproduce earlier, whereas those at lower risk can delay puberty and continue to invest resources in somatic growth. We examined relationships between a genetic predictor of infectious disease resistance, heterozygosity of the major histocompatibility complex (MHC), referred to as the human leukocyte antigen (HLA) gene in humans, and self-reported pubertal timing. In a combined sample of men from Canada (n = 137) and the United States (n = 43), MHC heterozygosity predicted later self-reported pubertal development. These findings suggest a genetic trade-off between immunocompetence and sexual maturation in human males.

What evolutionary processes maintain MHC IIꞵ diversity within and among populations of stickleback?

Major Histocompatibility Complex (MHC) genes code for proteins that recognize foreign protein antigens to initiate T‐cell‐mediated adaptive immune responses. They are often the most polymorphic genes in vertebrate genomes. How evolution maintains this diversity remains of debate. Three main hypotheses seek to explain the maintenance of MHC diversity by invoking pathogen‐mediated selection: heterozygote advantage, frequency‐dependent selection, and fluctuating selection across landscapes or through time. Here, we use a large‐scale field parasite survey in a stickleback metapopulation to test predictions derived from each of these hypotheses. We identify over 1000 MHC IIβ variants (alleles spanning paralogous genes) and find that many of them covary positively or negatively with parasite load, suggesting that these genes contribute to resistance or susceptibility. However, despite our large sample‐size, we find no evidence for the widely cited stabilizing selection on MHC heterozygosity, in which individuals with an intermediate number of MHC variants have the lowest parasite burden. Nor do we observe a rare‐variant advantage, or widespread fluctuating selection across populations. In contrast, we find that MHC diversity is best predicted by neutral genome‐wide heterozygosity and between‐population genomic divergence, suggesting neutral processes are important in shaping the pattern of metapopulation MHC diversity. Thus, although MHC IIβ is highly diverse and relevant to the type and intensity of macroparasite infection in these populations of stickleback, the main models of MHC evolution still provide little explanatory power in this system.

Spatiotemporal adaptive evolution of an MHC immune gene in a frog-fungus disease system.

Genetic diversity of major histocompatibility complex (MHC) genes is linked to reduced pathogen susceptibility in amphibians, but few studies also examine broad spatial and temporal patterns of MHC and neutral genetic diversity. Here, we characterized range-wide MHC diversity in the Northern leopard frog, Rana pipiens, a species found throughout North America that is experiencing disease-related declines. We used previously sequenced neutral markers (mitochondrial DNA and microsatellites), sequenced an expressed MHC class IIß gene fragment, and measured infection prevalence and intensity of the global fungal pathogen Batrachochytrium dendrobatidis (Bd) across 14 populations. Four populations were sampled across two decades, enabling temporal comparisons of selection and demography. We recovered 37 unique MHC alleles, including 17 that were shared across populations. Phylogenetic and population genetic patterns between MHC and neutral markers were incongruent, and five MHC codon positions associated with peptide binding were under positive selection. MHC heterozygosity, but not neutral marker heterozygosity, was a significant factor explaining spatial patterns of Bd prevalence, whereas only environmental variables predicted Bd intensity. MHC allelic richness (AR) decreased significantly over time but microsatellite-based AR did not, highlighting a loss of functional immunogenetic diversity that may be associated with Bd selective pressures. MHC supertype 4 was significantly associated with an elevated risk of Bd infection, whereas one supertype 2 allele was associated with a nearly significant reduced risk of Bd. Taken together, these results provide evidence that positive selection contributes to MHC class IIß evolution in R. pipiens and suggest that functional MHC differences across populations may contribute to disease adaptation.

MHC Class II Heterozygosity Associated With Attractiveness of Men and Women.

The genes of the Major Histocompatibility Complex (MHC), which plays a fundamental role in the immune system, are some of the most diverse genes in vertebrates and have been connected to mate choice in several species, including humans. While studies suggest a positive relationship between MHC diversity and male facial attractiveness, the connection of MHC diversity to other visual traits and female attractiveness is still unclear. The purpose of this study was to investigate further whether MHC heterozygosity, indicating genetic quality, is associated with visual traits affecting mate preferences in humans. In total 74 Latvian men and 49 women were genotyped for several MHC loci and rated for facial and, in men, also body attractiveness. The results indicate a preference for MHC heterozygous female and male faces. However, the initially positive relationship between MHC heterozygosity and facial attractiveness becomes non-significant in females, when controlling for multiple testing, and in males, when age and fat content is taken into account, referring to the importance of adiposity in immune function and thus also attractiveness. Thus overall the effect of MHC heterozygosity on attractiveness seems weak. When considering separate loci, we show that the main gene related to facial attractiveness is the MHC class II DQB1; a gene important also in viral infections and autoimmune diseases. Indeed, in our study, heterozygous individuals are rated significantly more attractive than their homozygous counterparts, only in relation to gene DQB1. This study is the first to indicate a link between DQB1 and attractiveness in humans.

No evidence for a relationship between MHC heterozygosity and life history strategy in a sample of North American undergraduates

Although allelic diversity at the major histocompatibility complex (MHC) has implications for adaptive immunity, mate choice, and social signalling, how diversity at the MHC influences the calibration of life history strategies remains largely uninvestigated. The current study investigated whether greater MHC heterozygosity was associated with markers of slower life history strategies in a sample of 789 North American undergraduates. Contrary to preregistered predictions and to previously published findings, MHC heterozygosity was not related to any of the psychological life history-relevant variables measured (including short- vs. long-term sexual strategy, temporal discounting, the Arizona life history battery, past and current health, disgust sensitivity, and Big Five personality traits). Further, no meaningful effects emerged when analysing women and men separately. Possible reasons for why the current results are inconsistent with previous work are discussed.

Selection of reproductive partners in semi-feral horses (Equus caballus) is not influenced by major histocompatibility complex (MHC): A field study

Major histocompatibility complex (MHC) is a suggested criterion of reproductive mate choice in many species. MHC-dissimilarity was suggested to play role in male selection by female horses (mares) in experimental settings. In our project, we asked whether under natural conditions mares choose breeding stallions guided by a certain MHC-type, either MHC-dissimilar or MHC-diverse.We observed the reproductive behavior of 26 mares and five stallions of semi-feral Konik Polski horses for eight years from which only 4 stallions and 16 mares could be used in analysis. Between-group (harems) migrations of mares and stallions and the composition of harems were noted. The choice of a reproductive partner was confirmed by observation (a mare present in the harem of a chosen stallion) and by the actual reproductive outcome (parentage of foals). The MHC of mares and stallions was tested using 11 MHC microsatellites. Genetic similarity in MHC was measured by pairwise relatedness and allele sharing between mares and stallions. MHC heterozygosity of every stallion was calculated.For all mares the choice of reproductive partner was the harem stallion. No extra-harem matings were observed. Allele sharing did not differ between mating pairs and between all of the possible combinations of mares and stallions (0.36 vs. 0.33; P = 0.66). Genetic similarity in MHC between mares and stallions did not influence the choice of reproductive partner by mares (P > 0.05), but mares tended (P = 0.08) to stay in harems of MHC-diverse stallion.The present findings suggest that mares in semi-feral conditions do not actively search for MHC dissimilar stallions, however they might favour MHC diverse ones. However, because the choice of reproductive partner was the current harem stallion, in the case of every mare we speculate that in feral conditions selection of reproductive stallion by mares might be either restricted or influenced by variety of factors other than MHC of a stallion.

MHC haplotype diversity in Icelandic horses determined by polymorphic microsatellites.

The Icelandic horse has been maintained as a closed population in its eponymous homeland for many generations, with no recorded introductions of new horses of any breed since the year 1000 CE. Here we determined the diversity of major histocompatibility complex (MHC) haplotypes in 156 Icelandic horses from two groups, based on a panel of 12 polymorphic intra-MHC microsatellites tested in families of various composition. We identified a total of 79 MHC haplotypes in these two groups, including one documented intra-MHC recombination event from a total of 147 observed meioses. None of these MHC haplotypes have been previously described in any other horse breed. Only one MHC homozygote was found in the entire population studied. These results indicate a very high level of MHC heterozygosity and haplotype diversity in the Icelandic horse. The environment in Iceland is remarkable for its lack of common agents of equine infectious disease, including equine herpesvirus type 1, influenza virus, and streptococcus equi. The driving forces for maintenance of MHC heterozygosity in Icelandic horses must thus be sought outside of these major horse pathogens. Based on our results, we propose that intra-MHC recombination may play a major role in the generation of novel haplotypes.

Facial masculinity does not appear to be a condition-dependent male ornament and does not reflect MHC heterozygosity in humans

Recent studies have called into question the idea that facial masculinity is a condition-dependent male ornament that indicates immunocompetence in humans. We add to this growing body of research by calculating an objective measure of facial masculinity/femininity using 3D images in a large sample (n = 1,233) of people of European ancestry. We show that facial masculinity is positively correlated with adult height in both males and females. However, facial masculinity scales with growth similarly in males and females, suggesting that facial masculinity is not exclusively a male ornament, as male ornaments are typically more sensitive to growth in males compared with females. Additionally, we measured immunocompetence via heterozygosity at the major histocompatibility complex (MHC), a widely-used genetic marker of immunity. We show that, while height is positively correlated with MHC heterozygosity, facial masculinity is not. Thus, facial masculinity does not reflect immunocompetence measured by MHC heterozygosity in humans. Overall, we find no support for the idea that facial masculinity is a condition-dependent male ornament that has evolved to indicate immunocompetence.

Heterozygosity-fitness correlation at the major histocompatibility complex despite low variation in Alpine ibex (Capra ibex).

Crucial for the long‐term survival of wild populations is their ability to fight diseases. Disease outbreaks can lead to severe population size reductions, which makes endangered and reintroduced species especially vulnerable. In vertebrates, the major histocompatibility complex (MHC) plays an important role in determining the immune response. Species that went through severe bottlenecks often show very low levels of genetic diversity at the MHC. Due to the known link between the MHC and immune response, such species are expected to be at particular risk in case of disease outbreaks. However, so far, only few studies have shown that low MHC diversity is correlated with increased disease susceptibility in species after severe bottlenecks. We investigated genetic variation at the MHC and its correlations with disease resistance and other fitness‐related traits in Alpine ibex (Capra ibex), a wild goat species that underwent a strong bottleneck in the last century and that is known to have extremely low genetic variability, both genome‐wide and at the MHC. We studied MHC variation in male ibex of Gran Paradiso National Park, the population used as a source for all postbottleneck reintroductions. We found that individual MHC heterozygosity (based on six microsatellites) was not correlated with genome‐wide neutral heterozygosity. MHC heterozygosity, but not genome‐wide heterozygosity, was positively correlated with resistance to infectious keratoconjunctivitis and with body mass. Our results show that genetic variation at the MHC plays an important role in disease resistance and, hence, should be taken into account for successfully managing species conservation.

Genes of the major histocompatibility complex highlight interactions of the innate and adaptive immune system.

BackgroundA well-functioning immune defence is crucial for fitness, but our knowledge about the immune system and its complex interactions is still limited. Major histocompatibility complex (MHC) molecules are involved in T-cell mediated adaptive immune responses, but MHC is also highly upregulated during the initial innate immune response. The aim of our study was therefore to determine to what extent the highly polymorphic MHC is involved in interactions of the innate and adaptive immune defence and if specific functional MHC alleles (FA) or heterozygosity at the MHC are more important.MethodsTo do this we used captive house sparrows (Passer domesticus) to survey MHC diversity and immune function controlling for several environmental factors. MHC class I alleles were identified using parallel amplicon sequencing and to mirror immune function, several immunological tests that correspond to the innate and adaptive immunity were conducted.ResultsOur results reveal that MHC was linked to all immune tests, highlighting its importance for the immune defence. While all innate responses were associated with one single FA, adaptive responses (cell-mediated and humoral) were associated with several different alleles.DiscussionWe found that repeated injections of an antibody in nestlings and adults were linked to different FA and hence might affect different areas of the immune system. Also, individuals with a higher number of different FA produced a smaller secondary response, indicating a disadvantage of having numerous MHC alleles. These results demonstrate the complexity of the immune system in relation to the MHC and lay the foundation for other studies to further investigate this topic.

No postcopulatory selection against MHC-homozygous offspring: Evidence from a pedigreed captive rhesus macaque colony.

The heterozygosity status of polymorphic elements of the immune system, such as the major histocompatibility complex (MHC), is known to increase the potential to cope with a wider variety of pathogens. Pre- and postcopulatory processes may regulate MHC heterozygosity. In a population where mating occurs among individuals that share identical MHC haplotypes, postcopulatory selection may disfavour homozygous offspring or ones with two MHC haplotypes identical to its mother. We tested these ideas by determining the incidence of MHC-heterozygous and MHC-homozygous individuals in a pedigreed, partially consanguineous captive rhesus monkey colony. Bayesian statistics showed that when parents share MHC haplotypes, the distribution of MHC-heterozygous and MHC-homozygous individuals significantly fitted the expected Mendelian distribution, both for the complete MHC haplotypes, and for MHC class I or II genes separately. Altogether, we found in this captive colony no evidence for postcopulatory selection against MHC-homozygous individuals. However, the distribution of paternally and maternally inherited MHC haplotypes tended to differ significantly from expected. Individuals with two MHC haplotypes identical to their mother were underrepresented and offspring with MHC haplotypes identical to their father tended to be overrepresented. This suggests that postcopulatory processes affect MHC haplotype combination in offspring, but do not prevent low MHC heterozygosity.

Positive selection drives the evolution of a major histocompatibility complex gene in an endangered Mexican salamander species complex.

Immune gene evolution can be critical to species survival in the face of infectious disease. In particular, polymorphism in the genes of the major histocompatibility complex (MHC) helps vertebrates combat novel and diverse pathogens by increasing the number of pathogen-derived proteins that can initiate the host's acquired immune response. In this study, we used a combination of presumably adaptive and neutral markers to investigate MHC evolution in populations of five salamander species within the Ambystoma velasci complex, a group consisting of 15 recently diverged species, several of which are endangered. We isolated 31 unique MHC class II β alleles from 75 total individuals from five species in this complex. MHC heterozygosity was significantly lower than expected for all five species, and we found no clear relationship between number of MHC alleles and species range, life history, or level of heterozygosity. We inferred a phylogeny representing the evolutionary history of Ambystoma MHC, with which we found signatures of positive selection on the overall gene, putative peptide-binding residues, and allelic lineages. We identified several instances of trans-species polymorphism, a hallmark of balancing selection observed in other groups of closely related species. In contrast, we did not detect comparable allelic diversity or signatures of selection on neutral loci. Additionally, we identified 17 supertypes among the 44 unique Ambystoma alleles, indicating that these sequences may encode functionally distinct MHC variants. We therefore have strong evidence that positive selection is a major evolutionary force driving patterns of MHC polymorphism in this recently radiated species complex.

Major histocompatibility complex and mate choice in the polygynous primate: the Sichuan snub‐nosed monkey (Rhinopithecus roxellana)

The highly polymorphic genes within the major histocompatibility complex (MHC) not only play a major role in immunity resistance, but also seem to provide hints for mate choice in some animal populations. In the present study we investigated MHC-related mate choice in a small natural population (group size 40-55 individuals) of a polygynous primate, the Sichuan snub-nosed monkey (Rhinopithecus roxellana). We found that there was no evidence either for MHC-disassortative mating, or for females to mate with males based on MHC heterozygosity or specific alleles. Nevertheless, of the 11 alleles identified, we found that the frequencies of 2 alleles, Rhro-DRB2 (P < 0.01) and Rhro-DRB5 (P < 0.05) were higher in offspring than in their parents. These findings suggest that MHC-DRB in this population of R. roxellana is unlikely to be associated with mating preferences. Limited female opportunities for mate choice are likely due, in part, to the harem breeding structure present in R. roxellana, and the relatively small number of resident adult males in our study band (N = 4-6). In addition, we suggest that differences in the frequency of particular alleles across generations may be linked to parasite resistance in a fluctuating environment; however, confirmation of this finding requires further study.

Pathogen burden, co-infection and major histocompatibility complex variability in the European badger (Meles meles).

Pathogen-mediated selection is thought to maintain the extreme diversity in the major histocompatibility complex (MHC) genes, operating through the heterozygote advantage, rare-allele advantage and fluctuating selection mechanisms. Heterozygote advantage (i.e. recognizing and binding a wider range of antigens than homozygotes) is expected to be more detectable when multiple pathogens are considered simultaneously. Here, we test whether MHC diversity in a wild population of European badgers (Meles meles) is driven by pathogen-mediated selection. We examined individual prevalence (infected or not), infection intensity and co-infection of 13 pathogens from a range of taxa and examined their relationships with MHC class I and class II variability. This population has a variable, but relatively low, number of MHC alleles and is infected by a variety of naturally occurring pathogens, making it very suitable for the investigation of MHC-pathogen relationships. We found associations between pathogen infections and specific MHC haplotypes and alleles. Co-infection status was not correlated with MHC heterozygosity, but there was evidence of heterozygote advantage against individual pathogen infections. This suggests that rare-allele advantages and/or fluctuating selection, and heterozygote advantage are probably the selective forces shaping MHC diversity in this species. We show stronger evidence for MHC associations with infection intensity than for prevalence and conclude that examining both pathogen prevalence and infection intensity is important. Moreover, examination of a large number and diversity of pathogens, and both MHC class I and II genes (which have different functions), provide an improved understanding of the mechanisms driving MHC diversity.

Major histocompatibility complex alleles associated with parasite susceptibility in wild giant pandas.

Major histocompatibility complex (MHC) polymorphism is thought to be driven by antagonistic coevolution between pathogens and hosts, mediated through either overdominance or frequency-dependent selection. However, investigations under natural conditions are still rare for endangered mammals which often exhibit depleted variation, and the mechanism of selection underlying the maintenance of characteristics remains a considerable debate. In this study, 87 wild giant pandas were used to investigate MHC variation associated with parasite load. With the knowledge of the MHC profile provided by the genomic data of the giant panda, seven DRB1, seven DQA1 and eight DQA2 alleles were identified at each single locus. Positive selection evidenced by a significantly higher number of non-synonymous substitutions per non-synonymous codon site relative to synonymous substitutions per synonymous codon site could only be detected at the DRB1 locus, which leads to the speculation that DRB1 may have a more important role in dealing with parasite infection for pandas. Coprological analyses revealed that 55.17% of individuals exhibited infection with 1-2 helminthes and 95.3% of infected pandas carried Baylisascaris shroederi. Using a generalized linear model, we found that Aime-DRB1*10 was significantly associated with parasite infection, but no resistant alleles could be detected. MHC heterozygosity of the pandas was found to be uncorrelated with the infection status or the infection intensity. These results suggested that the possible selection mechanisms in extant wild pandas may be frequency dependent rather than being determined by overdominance selection. Our findings could guide the candidate selection for the ongoing reintroduction or translocation of pandas.

Brief report: Parthenogenetic embryonic stem cells are an effective cell source for therapeutic liver repopulation.

Parthenogenesis is the development of an oocyte without fertilization. Mammalian parthenogenetic (PG) embryos are not viable, but can develop into blastocysts from which embryonic stem cells (ESCs) have been derived in mouse and human. PG ESCs are frequently homozygous for alleles encoding major histocompatibility complex (MHC) molecules. MHC homozygosity permits much more efficient immune matching than MHC heterozygosity found in conventional ESCs, making PG ESCs a promising cell source for cell therapies requiring no or little immune suppression. However, findings of restricted differentiation and proliferation of PG cells in developmental chimeras have cast doubt on the potential of PG ESC derivatives for organ regeneration. To address this uncertainty, we determined whether PG ESC derivatives are effective in rescuing mice with lethal liver failure due to deficiency of fumarylacetoacetate hydrolase (Fah). In developmental chimeras generated by injecting wild-type PG ESCs into Fah-deficient blastocysts, PG ESCs differentiated into hepatocytes that could repopulate the liver, provide normal liver function, and facilitate long-term survival of adult mice. Moreover, after transplantation into adult Fah-deficient mice, PG ESC-derived hepatocytes efficiently engrafted and proliferated, leading to high-level liver repopulation. Our results show that--despite the absence of a paternal genome--PG ESCs can form therapeutically effective hepatocytes.

Retracted: Heterozygosity, sexual ornament and body size in the crested newt

AbstractBoth genome‐wide heterozygosity and heterozygosity at major histocompatibility complex (MHC) genes are often associated with higher fitness. Recent theoretical work indicates that sexual ornaments may reveal information about individual heterozygosity, and that preference for such ornaments may benefit females via the increased heterozygosity of their progeny. Here, we used path analysis to investigate the direct and indirect (via body size used as an index of condition) effects of heterozygosity at six microsatellite loci and the MHC class II DAB gene on the size of a sexual ornament, the crest, in the crested newt Triturus cristatus. We found that microsatellite heterozygosity, but not MHC heterozygosity, significantly predicted male body size, and that male body size significantly predicted crest height. However, there was no direct effect of MHC or microsatellite heterozygosity on crest height. Furthermore, microsatellite heterozygosity significantly increased with age, indicating that it had a positive effect on survival. Overall, our results are consistent with the hypothesis that heterozygosity determines condition, and that variation in condition is expressed as variation in sexual ornamentation.