House sparrows do not exhibit a preference for the scent of potential partners with different MHC-I allele numbers and genetic distances

MHC genes play a fundamental role in immune recognition of pathogens and parasites. Therefore, females may increase offspring heterozygosity and genetic diversity by selecting MHC genetically compatible or heterozygous males. In birds, several studies suggest that MHC genes play a role in mate choice, and recent evidence suggest that olfaction may play a role in such discrimination. Previous studies indicated that house sparrow females with low allelic diversity prefer males with higher diversity in MHC-I alleles. Here, we directly explored whether both house sparrow females and males could estimate by scent the number in MHC amino acid and functional variants as well as the level of MHC-I similarity or dissimilarity of potential partners. Our results show that neither females nor males exhibit a preference related to the number of MHC-I amino acid variants or functional variants or in relation to MHC amino acid or functional similarity of potential partners, suggesting that MHC-I is not detected through olfaction. Further studies are needed to understand the mechanisms responsible for MHC-I based mate discrimination in birds.

Inbreeding Coefficient and Distance in MHC Genes of Parents as Predictors of Reproductive Success in Domestic Cat

Inbreeding and low diversity in MHC genes are considered to have a negative effect on reproductive success in animals. This study presents an analysis of the number and body mass of offspring in domestic cat, depending on the inbreeding coefficient and the degree of similarity in MHC genes of class I and II in parents. Inbred partners had a lower number of live kittens at birth than outbred ones. At the same time, the inbreeding coefficient did not affect the litter size and the number of offspring who survived until the period of transition to solid food. The most significant predictor for the number of surviving offspring was the degree of parental similarity in MHC genes: the parents with the maximum distance in MHC genes had more survived kittens. Moreover, this effect was most pronounced immediately after birth. A significant percentage of kittens from parents with a minimum distance in MHC genes were either stillborn or died on the first day after birth. By the age of transition to solid food, this effect is no longer so pronounced. Furthermore, neither the inbreeding coefficient nor the distance in MHC genes of parents had any effect on the body mass of kittens.

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.

Transcriptional Profiling of Monocytes Deficient in Nuclear Orphan Receptors NR4A2 and NR4A3 Reveals Distinct Signalling Roles Related to Antigen Presentation and Viral Response

The nuclear receptor sub-family 4 group A (NR4A) family are early response genes that encode proteins that are activated in several tissues/cells in response to a variety of stressors. The NR4A family comprises NR4A1, NR4A2 and NR4A3 of which NR4A2 and NR4A3 are under researched and less understood, particularly in the context of immune cells. NR4A expression is associated with multiple diseases e.g. arthritis and atherosclerosis and the development of NR4A-targetting molecules as therapeutics is a current focus in this research field. Here, we use a combination of RNA-sequencing coupled with strategic bioinformatic analysis to investigate the down-stream effects of NR4A2 and NR4A3 in monocytes and dissect their common and distinct signalling roles. Our data reveals that NR4A2 and NR4A3 depletion has a robust and broad-reaching effect on transcription in both the unstimulated state and in the presence of LPS. Interestingly, many of the genes affected were present in both the unstimulated and stimulated states revealing a previously unappreciated role for the NR4As in unstimulated cells. Strategic clustering and bioinformatic analysis identified both distinct and common transcriptional roles for NR4A2 and NR4A3 in monocytes. NR4A2 notably was linked by both bioinformatic clustering analysis and transcription factor interactome analysis to pathways associated with antigen presentation and regulation of MHC genes. NR4A3 in contrast was more closely linked to pathways associated with viral response. Functional studies further support our data analysis pointing towards preferential/selective roles for NR4A2 in the regulation of antigen processing with common roles for NR4A2 and NR4A3 evident with respect to cell migration. Taken together this study provides novel mechanistic insights into the role of the enigmatic nuclear receptors NR4A2 and NR4A3 in monocytes.

Genetics of Ankylosing Spondylitis—Focusing on the Ethnic Difference Between East Asia and Europe

Ankylosing spondylitis (AS) is a common, highly heritable inflammatory arthritis affecting the mainly axial joints in both East Asia and Europe. To date, the pathogenesis of AS is still unknown, although we know that genetics play a vital role in it. The HLA-B27 allele is found in over 85% of AS patients. However, strong evidence suggests that other major histocompatibility complex (MHC) and non-MHC genes are also involved in the pathogenesis. In addition, current data showed that there were significant differences in both genomics and metagenomics among the different ethnic populations. The investigation of the key role of the microbiome in AS pathogenesis also highlighted the host–microbiome genetic interactions. Here, we systematically review current AS genetic research data and further compare genetic differences, especially between East Asian and European groups, which may highlight the challenge in future genetic studies.

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 variability 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 variability 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, evidence of the indirect effect of the MHC via the microbiome. Our study provides support for the coupled role of MHC variability and microbial flora as contributing factors of parasite infection.

Ancient DNA reveals that few GWAS loci have been strongly selected during recent human history

Genetic data from ancient humans has provided new evidence in the study of loci thought to be under historic selection, and thus is a powerful tool for identifying instances of selection that might be missed by methods that use present-day samples alone. Using a curated set of disease-associated variants from the NHGRI-EBI GWAS Catalog, we provide an analysis to identify disease-associated variants that bear signatures of selection over time. After accounting for the fact that not every ancient individual contributed equally to modern genomes, a Bayesian inference method was used to infer allele frequency trajectories over time and determine which disease-associated loci exhibit signatures of natural selection. Of the 2,709 variants analyzed in this study, 895 show at least a weak signature of selection (|s| > 0.001), including multiple variants that are introgressed from Neanderthals. However, only nine disease-associated variants show a signature of strong selection (|s| > 0.01). Additionally, we find that many risk-associated alleles have increased in frequency during the past 10,000 years. Overall, we find that disease-associated variants from GWAS are governed by nearly neutral evolution. Exceptions to this broad pattern include GWAS loci that protect against asthma and variants in MHC genes. Ancient samples allow us an unprecedented look at how our species has changed over time, and our results represent an important early step in using this new source of data to better understand the evolution of hereditary disease risks.

The Invertebrate Antibody

Introduction Many researchers don’t believe in our works: they speak we are wrong when we evoke the Invertebrate Antibody...BUT: Discussion We have discovered, in the past, the sea star lymphocytes ( B and T sea star lymphocytes : cf Fig 1,2) : these cells of 4-5µ in diameter are smaller than Vertebrate lymphocytes And ...We discovered recently the IPA (Invertebrate Primitive Antibody) with the sea star IGKAPPA gene with IG sites (Meta Gene 2013). Therefore genomic data assert the evidence of primitive antibody in Echinodermata. Furthermore, we find MHC genes class I and class II in 2019 and Fab gene, Fc receptor gene in these Invertebrates

Molecular Characterization of MHC Class I Genes in Four Species of the Turdidae Family to Assess Genetic Diversity and Selection

In vertebrate animals, the molecules encoded by major histocompatibility complex (MHC) genes play an essential role in the adaptive immunity. MHC class I deals with intracellular pathogens (virus) in birds. MHC class I diversity depends on the consequence of local and global environment selective pressure and gene flow. Here, we evaluated the MHC class I gene in four species of the Turdidae family from a broad geographical area of northeast China. We isolated 77 MHC class I sequences, including 47 putatively functional sequences and 30 pseudosequences from 80 individuals. Using the method based on analysis of cloned amplicons ( n = 25 ) for each species, we found two and seven MHC I sequences per individual indicating more than one MHC I locus identified in all sampled species. Results revealed an overall elevated genetic diversity at MHC class I, evidence of different selection patterns among the domains of PBR and non-PBR. Alleles are found to be divergent with overall polymorphic sites per species ranging between 58 and 70 (out of 291 sites). Moreover, transspecies alleles were evident due to convergent evolution or recent speciation for the genus. Phylogenetic relationships among MHC I show an intermingling of alleles clustering among the Turdidae family rather than between other passerines. Pronounced MHC I gene diversity is essential for the existence of species. Our study signifies a valuable tool for the characterization of evolutionary relevant difference across a population of birds with high conservational concerns.