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444 results for “MHC”
Data from: Only rare classical MHC-I alleles are highly expressed in the European house sparrow
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Data from: Response to MHC-based olfactory cues in a mate choice context in two species of darter (Percidae: Etheostoma)
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Meta-analysis of major histocompatibility complex (MHC) class IIA reveals polymorphism and positive selection in many vertebrate species
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MHC class II genes mediate susceptibility and resistance to coronavirus infections in bats
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Relationship between genome-wide and MHC class I and II genetic diversity and complementarity in a nonhuman primate
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Correlated evolution of oxidative physiology and MHC-based immunosurveillance in birds
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Sequence-structure-function relationships in class I MHC: a local frustration perspective
<p>Class I Major Histocompatibility Complex (MHC) binds short antigenic peptides with the help of Peptide Loading Complex (PLC), and presents them to T-cell Receptors (TCRs) of cytotoxic T-cells and Killer-cell Immunglobulin-like Receptors (KIRs) of Natural Killer (NK) cells. With more than 10000 alleles, the Human Leukocyte Antigen (HLA) chain of MHC is the most polymorphic protein in humans. This allelic diversity provides a wide coverage of peptide sequence space, yet does not affect the three-dimensional structure of the complex. Moreover, TCRs mostly interact with pMHC in a common diagonal binding mode, and KIR-pMHC interaction is allele-dependent. With the aim of establishing a framework for understanding the relationships between polymorphism (sequence), structure (conserved fold) and function (protein interactions) of the MHC, we performed here a local frustration analysis on pMHC homology models covering 1436 HLA I alleles. An analysis of local frustration profiles indicated that (1) variations in MHC fold are unlikely due to minimally-frustrated and relatively conserved residues within the HLA peptide-binding groove, (2) high frustration patches on HLA helices are either involved in or near interaction sites of MHC with the TCR, KIR, or Tapasin of the PLC, and (3) peptide ligands mainly stabilize the F-pocket of HLA binding groove.</p>
Comparing raccoon MHC diversity in native and introduced ranges: evidence for the importance of functional immune diversity for adaptation and survival in novel environments.
<p>The adaptive potential of invasive species is related to the genetic <span class="il">diversity</span> of the invader, which is influenced by genetic drift and natural selection. Typically, the genetic <span class="il">diversity</span> of invaders is studied with neutral genetic markers, however, the expectation of reduced <span class="il">diversity</span> has not been consistently supported by empirical studies. Here, we describe and interpret genetic <span class="il">diversity</span> at both neutral microsatellite loci and the immune related <span class="il">MHC</span>-DRB locus of <span class="il">native</span> and invasive populations of <span class="il">raccoon</span> to better understand of how drift and selection impact patterns of genetic <span class="il">diversity</span> during the invasion process. We found that despite the loss of many <span class="il">MHC</span> alleles in comparison with <span class="il">native</span> populations, functional <span class="il">MHC</span> supertypes are preserved in the invasive region. In the <span class="il">native</span> <span class="il">raccoon</span> population the number of supertypes within individuals was higher than expected under a neutral model. The high level of individual functional divergence may facilitate the adaptation to local conditions in the invasive range. These results suggest that selection is driving divergent allele combinations despite drift causing allelic loss. In the invasive populations, we also detected increased population structure at microsatellites compared to the <span class="il">MHC</span> locus, further suggesting that balancing selection is acting on adaptively important regions of the <span class="il">raccoon</span> genome. Finally, we found that alleles known to exhibit resistance to rabies in the <span class="il">native</span> range, Prlo-DRB*4, Prlo-DRB*16 and Prlo-DRB*102, were the most common alleles in the European populations, suggesting directional selection is acting on this locus. Our research shows empirical support for the importance of functional immune <span class="il">diversity</span> for adaptation and survival in novel environments.</p>
Data from: Is MHC diversity a better marker for conservation than neutral genetic diversity? a case study of two contrasting dolphin populations
Genetic diversity is essential for populations to adapt to changing environments. Measures of genetic diversity are often based on selectively neutral markers, such as microsatellites. Genetic diversity to guide conservation management, however, is better reflected by adaptive markers, including genes of the major histocompatibility complex (MHC). Our aim was to assess MHC and neutral genetic diversity in two contrasting bottlenose dolphin (Tursiops aduncus) populations in Western Australia—one apparently viable population with high reproductive output (Shark Bay) and one with lower reproductive output that was forecast to decline (Bunbury). We assessed genetic variation in the two populations by sequencing the MHC class II DQB, which encompasses the functionally important peptide binding regions (PBR). Neutral genetic diversity was assessed by genotyping twenty‐three microsatellite loci. We confirmed that MHC is an adaptive marker in both populations. Overall, the Shark Bay population exhibited greater MHC diversity than the Bunbury population—for example, it displayed greater MHC nucleotide diversity. In contrast, the difference in microsatellite diversity between the two populations was comparatively low. Our findings are consistent with the hypothesis that viable populations typically display greater genetic diversity than less viable populations. The results also suggest that MHC variation is more closely associated with population viability than neutral genetic variation. Although the inferences from our findings are limited, because we only compared two populations, our results add to a growing number of studies that highlight the usefulness of MHC as a potentially suitable genetic marker for animal conservation. The Shark Bay population, which carries greater adaptive genetic diversity than the Bunbury population, is thus likely more robust to natural or human‐induced changes to the coastal ecosystem it inhabits.
Data from: 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 generally test hypotheses by assuming female choice and male-male competition, whether or not mate choice dynamics have been previously determined for the species under study. Here we examined 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 is extreme: both partners work together to fledge a single chick during the breeding season, a task that requires regularly traveling hundreds of kilometers to and from foraging grounds over a six to eight-week provisioning period. Using a five-year dataset unprecedented for this species (n=1027 adults and 925 chicks), we found a positive relationship between variation in female reproductive quality 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-DAB201 / Ocle-DAB201) 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 highlights the need to incorporate a broader ecological framework and sufficient sample sizes into studies of MHC-based mating patterns in wild populations in general.
Genetic associations of the non-MHC region with systemic sclerosis in a Han Chinese population
<p>Systemic sclerosis (SSc) is a complex autoimmune disease with unknown etiology and genetic factors contribute significantly to its pathogenesis. Several studies have identified multiple SSc-susceptible genes while the majority of them were discovered mainly in Caucasians. Recent studies have revealed significant genetic differences between different ethnicities, illustrating the importance of cross-ethnicity validation of candidate SNPs in SSc patients other than Caucasians. In this study, we recruited 1,059 SSc patients and 1,951 matched controls to validate the associations of those reported non-MHC polymorphisms in a Han Chinese population. We searched for the SNPs associated with SSc in the studies published from 2004 to 2019 through Google Scholar and PubMed with the keywords “systemic sclerosis” and “genetics”. In total, 101 SNPs were remained for validation. </p>
Gerra litúrgica. MHC
**CAT** Aquesta petita gerreta litúrgica del segle VIII va ser trobada al *castellum* de Sant Julià de Ramis. És de bronze i al coll té una inscripció que diu "Que el senyor conservi la vida a Sinde i a Ares". **ESP** Esta pequeña jarrita litúrgica del siglo VIII fue encontrada en el *castellum* de Sant Julià de Ramis. Es de bronce y en el cuello tiene una inscripción que dice "Que el señor conserve la vida a Sinde y en Ares". **ENG** This small liturgical jug from the 8th century was found in the *castellum* of Sant Julià de Ramis. It is made of bronze and on the neck it has an inscription that says "May the Lord preserve life in Sinde and Ares." Source: Objaverse 1.0 / Sketchfab
A pan-cetacean MHC amplicon sequencing panel developed and evaluated in combination with genome assemblies
<p>The major histocompatibility complex (MHC) is a highly polymorphic gene family that is crucial in immunity, and its diversity can be effectively used as a fitness marker for populations. Despite this, MHC remains poorly characterised in non-model species (e.g., cetaceans: whales, dolphins and porpoises) as high gene copy number variation, especially in the fast-evolving class I region, makes analyses of genomic sequences difficult. To date, only small sections of class I and IIa genes have been used to assess functional diversity in cetacean populations. Here, we undertook a systematic characterisation of the MHC class I and IIa regions in available cetacean genomes. We extracted full-length gene sequences to design pan-cetacean primers that amplified the complete exon2 from MHC class I and IIa genes in one combined sequencing panel. We validated this panel in 19 cetacean species and described 354 alleles for both classes. Furthermore, we identified likely assembly artefacts for many MHC class I assemblies based on the presence of class I genes in the amplicon data compared to missing genes from genomes. Finally, we investigated MHC diversity using the panel in 25 humpback and 30 southern right whales, including four paternity trios for humpback whales. This revealed copy-number variable class I haplotypes in humpback whales, which is likely a common phenomenon across cetaceans. These MHC alleles will form the basis for a cetacean branch of the Immuno-Polymorphism Database (IPD-MHC), a curated resource intended to aid in the systematic compilation of MHC alleles across several species, to support conservation initiatives.</p>
Limited associations between MHC diversity and reproductive success in a bird species with biparental care
<p>The selective pressure from pathogens on individuals can have direct consequences on reproduction. Genes from the major histocompatibility complex (MHC) are central to the vertebrate adaptive immune system and pathogen resistance. In species with biparental care, each sex has distinct reproductive roles and levels of investment, and due to a trade-off with immunity, one can expect different selective regimes acting upon the MHC of each parent. Here, we addressed whether couples combine each other's variation at MHC loci to increase their breeding success. Specifically, we used a 23-year dataset from a barn owl population (<em>Tyto alba</em>) to understand how MHC class Iα and IIβ functional divergence and supertypes of each parent were associated with clutch size and fledging success. We did not detect associations between MHC diversity or supertypes with the clutch size nor with the fledging success. In addition, to understand the relative contribution from the MHC of the genetic parents and the social parents, we analysed the fledging success using only a cross-fostered dataset. We found several associations of weak-to-moderate effect sizes between the father's MHC and fledging success: i) lower MHC-Iα divergence in the genetic father increases fledging success, which might improve paternal care during incubation, and ii) one and two MHC-IIβ DAB2 supertypes in the social father decrease and increase, respectively, fledging success, which may affect the paternal care after hatching. Furthermore, fledging success increased when both parents did not carry MHC-IIβ DAB1 supertype 2, which could suggest conditional effects of this supertype. Although our study relied on a substantial dataset, we showed that the associations between MHC diversity and reproductive success remain scarce and of complex interpretation in the barn owl. Moreover, our results highlighted the need to incorporate more than one proxy of reproductive success and several MHC classes to capture more complex associations.</p>
Template-specific optimization of NGS genotyping pipelines reveals allele-specific variation in MHC gene expression
<p>Using high-throughput sequencing for precise genotyping of multi-locus gene families, such as the Major Histocompatibility Complex (MHC), remains challenging, due to the complexity of the data and difficulties in distinguishing genuine from erroneous variants. Several dedicated genotyping pipelines for data from high-throughput sequencing, such as next-generation sequencing (NGS), have been developed to tackle the ensuing risk of artificially inflated diversity. Here, we thoroughly assess three such multi-locus genotyping pipelines for NGS data, the DOC method, AmpliSAS and ACACIA, using MHC class IIβ datasets of three-spined stickleback gDNA, cDNA, and "artificial" plasmid samples with known allelic diversity. We show that genotyping of gDNA and plasmid samples at optimal pipeline parameters was highly accurate and reproducible across methods. However, for cDNA data, gDNA-optimal parameter configuration yielded decreased overall genotyping precision and consistency between pipelines. Further adjustments of key clustering parameters were required tο account for higher error rates and larger variation in sequencing depth per allele, highlighting the importance of template-specific pipeline optimization for reliable genotyping of multi-locus gene families. Through accurate paired gDNA-cDNA typing and MHC-II haplotype inference, we show that MHC-II allele-specific expression levels correlate negatively with allele number across haplotypes. Lastly, sibship-assisted cDNA-typing of MHC-I revealed novel variants linked in haplotype blocks and a higher-than-previously-reported individual MHC-I allelic diversity. In conclusion, we provide novel genotyping protocols for the three-spined stickleback MHC-I and -II genes and evaluate the performance of popular NGS-genotyping pipelines. We also show that fine-tuned genotyping of paired gDNA-cDNA samples facilitates amplification bias-corrected MHC allele expression analysis.</p>
Source Data File – Dual role of the peptide loading complex as proofreader and limiter of MHC-I presentation – PNAS 2023-21600
<p>Source Data Files</p>
Geometric deep learning improves generalizability of MHC-bound peptide predictions
<p>Full dataset and trained models from the manuscript "<strong>Geometric deep learning improves generalizability of MHC-bound peptide predictions</strong>".</p> <p>"outputs_and-BA_data.zip" contains the networks' outputs for each cross-validation experiment and a "full_dataset.csv" containing the initial BA data.<br>Note: this file has been updated (2024/11/26) due to errors in generating some of the previous csvs. In the earlier version, both MLP and CNN outputs reported were wrong. The correct values are now reported in the updated csvs.</p> <p>"trained_models.zip" contains all the trained models parameters</p> <p>"propedia_ssl.zip" contains all the 3D models from propedia used to train the 3D-SSL</p> <p>"pdb.zip" contains 3D models generated in PANDORA and used to train CNN, GNN and EGNN. It amounts to 145665 .pdb files, one for each human binding affinity entry from the initial dataset from O'Donnell et al. The list of entries used to actually train networks after filtering can be found in outputs_and-BA_data.zip", in the "full_dataset.csv" file. </p> <p> </p> <p>CHANGELOG v4:</p> <p>- In outputs_and-BA-data.zip, updated CNN_AlleleClustered_test_crossval.csv and CNN_shuffled_test_crossval.csv. These file had the wrong IDs paired with the network outputs.The IDs and labels are now consistent with the outputs.</p> <p>- Updated reference from the preprint to the published article. </p> <p> </p>
Archived data for: Balancing selection, genetic drift, and human mediated-introgression interplay to shape MHC (functional) diversity in Mediterranean brown trout
<p>The extraordinary polymorphism of Major Histocompatibility Complex (MHC) genes is considered a paradigm of pathogen-mediated balancing selection, although empirical evidence is still scarce. Furthermore, the relative contribution of balancing selection to shape MHC population structure and diversity, compared to that of neutral forces, as well as its interaction with other evolutionary processes such as hybridization, remains largely unclear. To investigate these issues, we analysed adaptive (MHC-DAB gene) and neutral (11 microsatellite loci) variation in 156 brown trout (<i>Salmo trutta </i>complex) from six wild populations in central Italy exposed to introgression from domestic hatchery lineages (assessed with the LDH gene). MHC diversity and structuring correlated with those at microsatellites, indicating the substantial role of neutral forces. However, individuals carrying locally rare MHC alleles/supertypes (regardless of the zygosity status and degree of sequence dissimilarity of MHC) were in better body condition (a proxy of individual fitness/parasite load), hence supporting balancing selection under rare allele advantage, but not heterozygote advantage or divergent allele advantage. The association between specific MHC supertypes and body condition confirmed in part this finding. Across populations, MHC allelic richness increased with increasing admixture between native and domestic lineages, indicating introgression as a source of MHC variation. Furthermore, introgression across populations appeared more pronounced for MHC than microsatellites, possibly because initially-rare MHC variants are expected to introgress more readily under rare allele advantage. Providing evidence for the complex interplay among neutral evolutionary forces, balancing selection and human-mediated introgression in shaping the pattern of MHC (functional) variation, our findings contribute to a deeper understanding of the evolution of MHC genes in wild populations exposed to anthropogenic disturbance.</p>
MHC class II genotype-by-pathogen genotype interaction for infection prevalence in a natural rodent-Borrelia system
<p><span>MHC genes are extraordinarily polymorphic in most taxa. Host-pathogen coevolution driven by negative frequency-dependent selection (NFDS) is one of the main hypotheses for the maintenance of such immunogenetic variation. Here we test a critical but rarely tested assumption of this hypothesis—that MHC alleles affect resistance/susceptibility to a pathogen in a strain-specific way, i.e. that there is a host genotype-by-pathogen genotype interaction. </span><span>In a field study of bank voles naturally infected with the tick-transmitted bacterium </span><em><span>Borrelia afzelii</span></em><span>, we tested for MHC class II (</span><em><span>DQB</span></em><span>) genotype-by-</span><span><em>B. afzelii</em> </span><span>strain interactions for infection prevalence between ten </span><em><span>DQB</span></em><span><em> </em>alleles and seven strains. One allele (<em>DQB</em>*37) showed an interaction</span><span>, </span><span>such that voles carrying <em>DQB</em>*37 had higher prevalence of two strains and lower prevalence of one strain than individuals without the allele. These findings were corroborated by analyses of strain composition of infections, which revealed an effect of <em>DQB</em>*37 in the form of lower </span><span>b</span><span> diversity among infections in voles carrying the allele. Taken together, these results provide rare support at the molecular genetic level for a key assumption of models of antagonistic coevolution through NFDS. </span></p>
Salamanders reveal novel trajectories of amphibian MHC evolution
<p><span>Genes of the Major Histocompatibility Complex (MHC) code for immune proteins that are crucial for pathogen recognition in vertebrates. MHC research in non-model taxa has long been hampered by its genomic complexity that makes the locus-specific genotyping challenging. The recent progress in sequencing and genotyping methodologies allows an extensive phylogenetic coverage in studies of MHC evolution. Here, we analysed the peptide-binding region of MHC class I in 30 species of salamanders from six families representative of Urodela phylogeny. This extensive dataset revealed an extreme diversity of MHC-I in salamanders, both in terms of sequence diversity (ca. 3000 variants) and architecture (2-22 gene copies per species). The signal of positive selection was moderate and consistent between both peptide binding domains, but varied greatly between genera. Positions of positively selected sites mostly coincided with human Peptide Binding Sites, suggesting similar structural properties of MHC-I molecules across distant vertebrate lineages. Finally, we provided evidence for the common intra-exonic recombination at MHC-I and for the role of life-history traits in the processes of MHC-I expansion/contraction. Our study revealed novel evolutionary trajectories of amphibian MHC and it contributes to the understanding of the mechanisms that generated extraordinary MHC diversity throughout vertebrate evolution.</span></p>
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