Evidence of MHC class I and II influencing viral and helminth infection via the microbiome in a non-human primate

Until recently, the study of major histocompability complex (MHC) mediated immunity has focused on the direct link between MHC diversity and susceptibility to parasite infection. However, MHC genes can also influence host health indirectly through the sculpting of the bacterial community that in turn shape immune responses. We investigated the links between MHC class I and II gene diversity gut microbiome diversity and micro- (adenovirus, AdV) and macro- (helminth) parasite infection probabilities in a wild population of non-human primates, mouse lemurs of Madagascar. This setup encompasses a plethora of underlying interactions between parasites, microbes and adaptive immunity in natural populations. Both MHC classes explained shifts in microbiome composition and the effect was driven by a few select microbial taxa. Among them were three taxa (Odoribacter, Campylobacter and Prevotellaceae-UCG-001) which were in turn linked to AdV and helminth infection status, correlative evidence of the indirect effect of the MHC via the microbiome. Our study provides support for the coupled role of MHC diversity and microbial flora as contributing factors of parasite infection.

Mate choice for major histocompatibility complex (MHC) complementarity in the Yellow-rumped Flycatcher (Ficedula zanthopygia)

Background Genes of the major histocompatibility complex (MHC) are an important component of the vertebrate immune system and play a significant role in mate choice in animal populations. However, the MHC genetic targets of female mate choice have not been clearly identified, and whether female mate choice is based on neutral genetic characteristics remains an open question. Here, we focus on the effects of morphological traits and genetic similarity among individuals in MHC class IIB (MHC IIB) exon 2 on mating in a sexually dimorphic songbird that exhibits social monogamy with extra-pair paternity (EPP). Methods We sequenced 64 parent–offspring triads sampled over a 3-year period using two MHC class II loci to detect disassortative mating in the Yellow-rumped Flycatcher (Ficedula zanthopygia). Results We found that MHC similarity in social pairs was lower than that in random pairs. Extra-pair mate choice according to MHC IIB was observed, in which females’ extra-pair mates had fewer MHC alleles than their within-pair mates, but there was no significant band-sharing between extra-pair sires and potential extra-pair mates. However, the interaction between the MHC diversity of females and that of the social males affected the occurrence of EPP. Conclusions Our results support the “optimality hypothesis” of MHC-based social and extra-pair choice. Female choice probably maintains a certain level of MHC diversity in offspring in the Yellow-rumped Flycatcher.

High Levels of Genetic Variation in MHC-Linked Microsatellite Markers from Native Chicken Breeds

The major histocompatibility complex (MHC) is a highly polymorphic gene region that regulates cellular communication in all specific immune responses. In this study, we investigated 11 microsatellite (MS) markers in the MHC-B region of chicken populations from four countries: Sri Lanka, Bangladesh, South Korea, and Nigeria. The MS markers were divided into two sets. Set 1 included five novel MS markers, which we assessed using 192 samples from 21 populations. Set 2 included six previously reported markers, which we assessed using 881 samples from 29 populations. The Set 1 MS markers had lower polymorphism (polymorphic information content (PIC) < 0.5) than the Set 2 markers (PIC = 0.4–0.9). In all populations, the LEI0258 marker was the most polymorphic, with a total of 38 alleles (PIC = 0.912, expected heterozygosity (He) = 0.918). Local populations from Sri Lanka, Bangladesh, and Nigeria had higher allele diversity and more haplotypes for Set 2 MS markers than Korean and commercial populations. The Sri Lankan Karuwalagaswewa village population had the highest MHC diversity (mean allele number = 8.17, He = 0.657), whereas the white leghorn population had the lowest (mean allele number = 2.33, He = 0.342). A total of 409 haplotypes (89 shared and 320 unique), with a range of 4 (Rhode Island red) to 46 (Karuwalagaswewa village (TA)), were identified. Among the shared haplotypes, the B21-like haplotype was identified in 15 populations. The genetic relationship observed in a neighbour-joining tree based on the DA distance agreed with the breeding histories and geographic separations. The results indicated high MHC diversity in the local chicken populations. The difference in the allelic pattern among populations presumably reflects the effects of different genotypes, environments, geographic variation, and breeding policies in each country. The selection of MHC allele in domestic poultry can vary due to intensification of poultry production. Preserved MHC diversity in local chicken provides a great opportunity for future studies that address the relationships between MHC polymorphisms and differential immune responses.

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.

Genetic origins and diversity of bushpigs from Madagascar (Potamochoerus larvatus, family Suidae)

The island of Madagascar, situated off the southeast coast of Africa, shows the first evidence of human presence ~ 10,000 years ago; however, other archaeological data indicates a settlement of the modern peoples of the island distinctly more recent, perhaps > 1500 years ago. Bushpigs of the genus Potamochoerus (family Suidae), are today widely distributed in Madagascar and presumed to have been introduced from Africa at some stage by human immigrants to the island. However, disparities about their origins in Madagascar have been presented in the literature, including the possibility of endemic subspecies, and few empirical data are available. Furthermore, the separation of bushpigs in Madagascar from their mainland relatives may have favoured the evolution of a different repertoire of immune genes first due to a founder effect and then as a response to distinct pathogens compared to their ancestors. Molecular analysis confirmed the species status of the bushpig in Madagascar as P. larvatus, likely introduced from the central region of southern Africa, with no genetic evidence for the recognition of eastern and western subspecies as suggested from previous cranial morphology examination. Investigation of the immunologically important SLA-DQB1 peptide-binding region showed a different immune repertoire of bushpigs in Madagascar compared to those on the African mainland, with seventeen exon-2 haplotypes unique to bushpigs in Madagascar (2/28 haplotypes shared). This suggests that the MHC diversity of the Madagascar populations may have enabled Malagasy bushpigs to adapt to new environments.

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

Major Histocompatibility Complex (MHC) genes encode 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 is still an unsettled issue. 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 a thousand MHCIIβ alleles 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 alleles have the lowest parasite burden. Nor do we observe a rare-allele 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 MHCIIβ 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.

Mating preferences can drive expansion or contraction of major histocompatibility complex gene family

Major histocompatibility complex (MHC)-based mating rules can evolve as a way to avoid inbreeding or to increase offspring immune competence. While the role of mating preference in shaping the MHC diversity in vertebrates has been acknowledged, its impact on individual MHC diversity has not been considered. Here, we use computer simulations to investigate how simple mating rules favouring MHC-dissimilar partners affect the evolution of the number of MHC variants in individual genomes, accompanying selection for resistance to parasites. We showed that the effect of such preferences could sometimes be dramatic. If preferences are aimed at avoiding identical alleles, the equilibrium number of MHC alleles is much smaller than under random mating. However, if the mating rule minimizes the ratio of shared to different alleles in partners, MHC number is higher than under random mating. Additionally, our simulations revealed that a negative correlation between the numbers of MHC variants in mated individuals can arise from simple rules of MHC-disassortative mating. Our results reveal unexpected potential of MHC-based mating preferences to drive MHC gene family expansions or contractions and highlight the need to study the mechanistic basis of such preferences, which is currently poorly understood.

MHC-associated mate choice under competitive conditions in captive versus wild Tasmanian devils

Mate choice contributes to driving evolutionary processes when animals choose breeding partners that confer genetic advantages to offspring, such as increased immunocompetence. The major histocompatibility complex (MHC) is an important group of immunological molecules, as MHC antigens bind and present foreign peptides to T-cells. Recent studies suggest that mates may be selected based on their MHC profile, leading to an association between an individual’s MHC diversity and their breeding success. In conservation, it may be important to consider mate choice in captive breeding programs, as this mechanism may improve reproductive rates. We investigated the reproductive success of Tasmanian devils in a group housing facility to determine whether increased MHC-based heterozygosity led individuals to secure more mating partners and produce more offspring. We also compared the breeding success of captive females to a wild devil population. MHC diversity was quantified using 12 MHC-linked microsatellite markers, including 11 previously characterized markers and one newly identified marker. Our analyses revealed that there was no relationship between MHC-linked heterozygosity and reproductive success either in captivity or the wild. The results of this study suggest that, for Tasmanian devils, MHC-based heterozygosity does not produce greater breeding success and that no specific changes to current captive management strategies are required with respect to preserving MHC diversity.

Latitudinal MHC variation and haplotype associated differential survival in response to experimental infection of two strains of Batrachochytrium dendrobatitis (Bd-GPL) in common toads

While both innate and adaptive immune system mechanisms have been implicated in resistance against the chytrid fungus Batrachochytrium dendrobatitis, studies on the role of specific MHC haplotypes on Bd infection are rare. Here, we studied latitudinal variation in MHC Class IIB loci along a latitudinal gradient from southern to northern Sweden in common toads, Bufo bufo. Swedish toad populations had fewer MHC Class IIB haplotypes compared to a previous study of populations in Britain. Furthermore, we found MHC diversity to decline from south to the north within Sweden. The low diversity may compromise the ability of northern populations to fight emerging disease, such as the chytrid fungus Bd. In a laboratory experiment, we infected newly metamorphosed toads with two strains of the Global Pandemic Lineage of the fungus (Bd-GPL) and compared survival with sham controls. We found Bd-infected toads had lower survival compared to controls. Survival was dependent on Bd-strain and whether experimental toads where collected in the south or the north of Sweden with lower survival in northern individuals. MHC diversity was lower in toads of northern origin, all northern animals being monomorphic for a single MHC haplotype, whereas we found seven different haplotypes in southern animals. Survival of infected animals was dependent on both Bd-strain and MHC haplotype suggesting differential infection dynamics depending on both Bd-strain and host MHC characteristics.