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63 results for “MHC genes”
High MHC gene copy number maintains diversity despite homozygosity in a Critically Endangered single-island endemic bird, but no evidence of MHC-based mate choice
<p>Raw sequence data from two amplicon libraries of MHC class I exon 3 of Raso Lark <em>Alauda razae</em>, sequenced on an Illumina Miseq. The two different libraries (two different Illumina runs) are collected in separat tar archive (.tar). Within each of those are individual sequence reads as gzipped fastq files (.fastq.gz). Each sample has two files, one for read 1 (R1) and one for read 2 (R2), with file names structured as follows. Delimited by underscore (_) are:</p> <ol> <li>sample name as referred to in the data and paper (“RingNo” in the Supporting data table);</li> <li>formal ID (also referred to in data table, often corresponding to full ring number);</li> <li>Illumina sample number (i.e. based on the order that samples are listed in the sample sheet);</li> <li>Illumina lane number (static as L001, as Miseq instruments have a single lane on their flow cells);</li> <li>read number (R1 [forward] or R2 [reverse]);</li> <li>static identifier from Illumina (001).</li> </ol> <p>Thus, the file 83304_TJ83304_S163_L001_R2_001.fastq.gz is the reverse (read 2) MHC class I exon 3 sequence of individual 83304 (ring number TJ83304).</p>
Individual allotype responses to HEK-293T-based cell lines ex-pressing single MHC class I chain-related gene B alleles
<p><span>Figure S1.</span><span> Individual allotype responses between 64 sera collected from kidney transplant patients and 5 single </span><span>MICB</span><span> allele-expressing cell lines established in </span><span>HLA</span><span> class I, </span><span>MICA,</span><span> and </span><span>MICB</span><span>-null HEK-293T cells. </span><span>HLA</span><span> class I, </span><span>MICA,</span><span> and </span><span>MICB</span><span> genes were removed using CRISPR/Cas9 in previous studies [20, 21]. Some of the 64 sera showed responses to single </span><span>MICA</span><span> allele-expressing cell lines [21]. However, none of the 64 sera showed individual allotype responses in this study.</span></p>
MHC class II genes mediate susceptibility and resistance to coronavirus infections in bats
<p>Understanding the immunogenetic basis of coronavirus (CoV) susceptibility in major pathogen reservoirs, such as bats, is central to infer their zoonotic potential. Members of the cryptic <em>Hipposideros</em> bat species complex differ in CoV susceptibility, but the underlying mechanisms remain unclear. The genes of the major histocompatibility complex (MHC) are the best understood genetic basis of pathogen resistance, and differences in MHC diversity are one possible reason for asymmetrical infection patterns among closely related species. Here, we aimed to link asymmetries in observed CoV (CoV-229E, CoV-2B, and CoV-2Bbasal) susceptibility to immunogenetic differences amongst four <em>Hipposideros</em> bat species. From the 2,072 bats assigned to their respective species using the mtDNA cytochrome b gene, members of the most numerous and ubiquitous species, <em>Hipposideros caffer</em> D, were most infected with CoV-229E and SARS-related CoV-2B. Using a subset of 569 bats we determined that much of the existent allelic and functional (i.e., supertype) MHC DRB class II diversity originated from common ancestry. One MHC supertype shared amongst all species, ST12, was consistently linked to susceptibility with CoV-229E, which is closely related to the common cold agent HCoV-229E, and infected bats with ST12 had a lower body condition. The same MHC supertype was connected to resistance to CoV-2B, and bats with ST12 were less likely be co-infected with CoV-229E and CoV-2B. Our work suggests a role of immunogenetics in determining CoV susceptibility in bats. We advocate for the preservation of functional genetic and species diversity in reservoirs as means of mitigating the risk of disease spillover.</p>
MHC class II genes mediate susceptibility and resistance to coronavirus infections in bats
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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>
Data from: Evolutionary variation in gene conversion at the avian MHC is explained by fluctuating selection, gene copy numbers, and life history
<p>The Major Histocompatibility Complex (MHC) multigene family encodes key pathogen-recognition molecules of the vertebrate adaptive immune system. Hyper-polymorphism of MHC genes is <em>de novo</em> generated by point mutations, but new haplotypes may also arise by re-shuffling of existing variation through intra- and inter-locus gene conversion. Although the occurrence of gene conversion at the MHC has been known for decades, we still have limited understanding of its functional importance. Here, I took advantage of extensive genetic resources (~9000 sequences) to investigate a broad scale macroevolutionary patterns in gene conversion processes at the MHC across nearly 200 avian species. Gene conversion was found to constitute a universal mechanism in birds, as 83% of species showed footprints of gene conversion at either MHC class and 25% of all allelic variants were attributed to gene conversion. Gene conversion processes were stronger at MHC-II than MHC-I, but inter-specific variation at both MHC classes was explained by similar evolutionary scenarios, reflecting fluctuating selection towards different optima and drift. Gene conversion showed uneven phylogenetic distribution across birds and was driven by gene copy number variation, supporting significant role of inter-locus gene conversion processes in the evolution of the avian MHC. Finally, MHC gene conversion was stronger in species with fast life histories (high fecundity) and in long-distance migrants, likely reflecting variation in population sizes and host-pathogen coevolutionary dynamics. The results provide a robust comparative framework for understanding macroevolutionary variation in gene conversion at the avian MHC and reinforce important contribution of this mechanism to functional MHC diversity.</p>
Mating preferences can drive expansion or contraction of MHC gene family
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 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, e.g. under strong selection against sib-mating, the equilibrium number of MHC alleles is much smaller than under random mating. However, if the mating rule minimises 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.
Interspecific introgression of MHC genes in Triturus newts: Evidence from multiple contact zones
<p>The major histocompatibility complex (MHC) genes are central to the adaptive immune response in vertebrates. Selection generally maintains high MHC variation because the spectrum of recognised pathogens depends on MHC polymorphism. Novel alleles favoured by selection originate by interallelic recombination or <em>de</em> <em>novo</em> mutations but may also be acquired by introgression from related species. However, the extent and prevalence of MHC introgression remain an open question. In this study, we tested for MHC introgression in six hybrid zones formed by six <em>Triturus</em> newt species. We sequenced and genotyped the polymorphic second exons of the MHC class I and II genes and compared their interspecific similarity at various distances from the centre of the hybrid zone. We found evidence for introgression of both MHC classes in the majority of examined hybrid zones, with support for a more substantial class I introgression. Furthermore, the overall MHC allele sharing outside of hybrid zones was elevated between pairs of <em>Triturus</em> species with abutting ranges, regardless of the phylogenetic distance between them. No effect of past hybrid zone movement on MHC allele sharing was found. Finally, using previously published genome-wide data, we demonstrated that MHC introgression was more extensive than genome-wide introgression, supporting its adaptive potential. Our study thus provides evidence for the prevalence of MHC introgression across multiple <em>Triturus</em> hybrid zones, indicating that MHC introgression between divergent hybridising species may be widespread and adaptive.</p>
Trans-specific polymorphism and the convergent evolution of supertypes in MHC class II genes in Darters (Etheostoma)
<p>Major Histocompatibility Complex (MHC) genes are one of the most polymorphic gene groups known in vertebrates. MHC genes also exhibit allelic variants that are shared among taxa, referred to as trans-specific polymorphism (TSP). The role that selection plays in maintaining such high diversity within species, as well as TSP, is an ongoing discussion in biology. In this study we used deep-sequencing techniques to characterize MHC class IIb gene diversity in three sympatric species of darters. We found at least 5 copies of the MHC gene in darters, with 126 genetic variants encoding 122 unique amino acid sequences. We identified four supertypes based on the binding properties of proteins encoded by the sequences. Although each species had a unique pool of variants, many variants were shared between species pairs and across all three species. Phylogenetic analysis showed that the variants did not group together monophyletically based on species identity or on supertype. An expanded phylogenetic analysis showed that some darter alleles grouped together with alleles from other percid fishes. Our findings show that TSP occurs in darters, which suggests that balancing selection is acting at the genotype level. Supertypes, however, are most likely evolving convergently, as evidenced by the fact that alleles do not form monophyletic groups based on supertype. Our research demonstrates that selection may be acting differently on MHC genes at the genotype and supertype levels, selecting for the maintenance of high genotypic diversity while driving the convergent evolution of similar MHC phenotypes across different species.</p>
Widespread introgression of MHC genes in Iberian Podarcis lizards
<p>Major Histocompatibility Complex (MHC) genes are crucial for the adaptive immune response of jawed vertebrates. Their variation, reaching extreme levels, is driven mainly by an arms race between hosts and pathogens. One hypothesized mechanism contributing to MHC polymorphism is adaptive introgression, the exchange of genetic variants between hybridizing species favoured by selection, yet its effect on MHC variation is poorly understood. Detection of adaptive MHC introgression, though challenging, may be facilitated by the analysis of species complexes forming multiple hybrid zones. Here, we investigated MHC introgression in six hybrid zones formed by seven species of <em>Podarcis</em> lizards inhabiting the Iberian Peninsula. To differentiate adaptive introgression from neutral introgression, we compared the patterns of gene exchange in MHC and genome-wide markers. We found elevated sharing of MHC alleles in the proximity of contact beyond the areas of detectable genome-wide admixture in most hybrid zones and, in half of them, asymmetric MHC exchange. In general, the elevated MHC allele sharing between species pairs with abutting ranges compared to geographically isolated species pairs also supports the prevalence of introgression. Collectively, our results demonstrate widespread MHC introgression in the Iberian <em>Podarcis</em> complex and suggest its adaptiveness. Contrary to previous results from <em>Triturus</em> newts, we did not observe differences in the rate of introgression between MHC classes. Our work adds support to the emerging view of adaptive introgression as a key mechanism shaping MHC diversity. It also raises questions about the effect of elevated MHC variation and factors leading to the asymmetry of adaptive introgression.</p>
Data from: The quest for good genes: epigamic traits, fitness, MHC and multilocus heterozygosity in the guppy
<p><span>The "good genes" hypothesis for the evolution of male secondary sexual traits poses that female preferences for such traits are driven by indirect genetic benefits. However, support for the hypothesis remains ambiguous, and, in particular, the genetic basis for the benefits has rarely been investigated. Here, we use semi-natural populations of Trinidadian guppies to investigate whether sexually selected traits (orange, black and iridescent colouration, gonopodium length and body size) predict fitness measured as the number of grandoffspring, a metric that integrates across fitness components and sexes. Furthermore, we tested whether two potential sources of genetic benefits – major histocompatibility complex (MHC) genotypes and multilocus heterozygosity (MLH) – are significant predictors of fitness and of the size of sexually selected traits. We found a significant, non-linear effect of the area of black pigmentation and male body size on the number of grandoffspring, suggesting stabilising selection on black area, and non-linear selection favouring small body size. MLH was heritable (h<sup>2</sup> = 0.14) and significantly predicted the number of grandoffspring, indicating the potential for genetic benefits based on heterozygosity. We also found support for local heterozygosity effects, which may reflect a non-even distribution of genetic load across the genome. MHC genotype was not significantly associated with any tested fitness component, or with the load of <em>Gyrodactylus</em> parasites. Neither MHC nor MLH was a significant predictor of sexually selected traits. Overall, our results highlight the role of heterozygosity in determining fitness but do not provide support for male sexually selected traits being indicators of genetic quality. </span></p>
Data from: Evolutionary variation in gene conversion at the avian MHC is explained by fluctuating selection, gene copy numbers, and life history
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Widespread introgression of MHC genes in Iberian Podarcis lizards
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Data from: The quest for good genes: epigamic traits, fitness, MHC and multilocus heterozygosity in the guppy
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Interspecific introgression of MHC genes in Triturus newts: Evidence from multiple contact zones
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Template-specific optimization of NGS genotyping pipelines reveals allele-specific variation in MHC gene expression
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Trans-specific polymorphism and the convergent evolution of supertypes in MHC class II genes in Darters (Etheostoma)
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Insights from the timber rattlesnake (<em>Crotalus horridus</em>) genome for MHC gene architecture and evolution in threatened rattlesnakes
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Data from: Patterns of genetic differentiation at MHC class I genes and microsatellites identify conservation units in the giant panda
Background: Evaluating patterns of genetic variation is important to identify conservation units (i.e., evolutionarily significant units [ESUs], management units [MUs], and adaptive units [AUs]) in endangered species. While neutral markers could be used to infer population history, their application in the estimation of adaptive variation is limited. The capacity to adapt to various environments is vital for the long-term survival of endangered species. Hence, analysis of adaptive loci, such as the major histocompatibility complex (MHC) genes, is critical for conservation genetics studies. Here, we investigated 4 classical MHC class I genes (Aime-C, Aime-F, Aime-I, and Aime-L) and 8 microsatellites to infer patterns of genetic variation in the giant panda (Ailuropoda melanoleuca) and to further define conservation units. Results: Overall, we identified 24 haplotypes (9 for Aime-C, 1 for Aime-F, 7 for Aime-I, and 7 for Aime-L) from 218 individuals obtained from 6 populations of giant panda. We found that the Xiaoxiangling population had the highest genetic variation at microsatellites among the 6 giant panda populations and higher genetic variation at Aime-MHC class I genes than other larger populations (Qinling, Qionglai, and Minshan populations). Differentiation index (FST)-based phylogenetic and Bayesian clustering analyses for Aime-MHC-I and microsatellite loci both supported that most populations were highly differentiated. The Qinling population was the most genetically differentiated. Conclusions: The giant panda showed a relatively higher level of genetic diversity at MHC class I genes compared with endangered felids. Using all of the loci, we found that the 6 giant panda populations fell into 2 ESUs: Qinling and non-Qinling populations. We defined 3 MUs based on microsatellites: Qinling, Minshan-Qionglai, and Daxiangling-Xiaoxiangling-Liangshan. We also recommended 3 possible AUs based on MHC loci: Qinling, Minshan-Qionglai, and Daxiangling-Xiaoxiangling-Liangshan. Furthermore, we recommend that a captive breeding program be considered for the Qinling panda population.
Data from: Cryptic haplotype-specific gamete selection yields offspring with optimal MHC immune genes
Females choose specific mates in order to produce fitter offspring. However, several factors interfere with females' control over fertilization of their eggs, including sneaker males and phenotypically unpredictable allele segregation during meiosis. Mate choice at the individual level thus provides only a poor approximation for obtaining the best genetic match. Consequently, post-copulatory sperm selection by female oocytes has been proposed as a mechanism to achieve complementary combinations of parental haplotypes. Here, using controlled in vitro fertilization of three-spined stickleback eggs, we find haplotype-specific fertilization bias towards gametes with complementary major histocompatibility complex (MHC) immunogenes. The resulting zygote (and thus offspring) genotypes exhibit an intermediate level of individual MHC diversity that was previously shown to confer highest pathogen resistance. Our finding of haplotype-specific gamete selection thus represents an intriguing mechanism for fine-tuned optimization of the offspring's immune gene composition and an evolutionary advantage in the Red Queen dynamics of host-parasite coevolution.
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