Tracing the Dynamical Genetic Diversity Changes of Russian Livni Pigs during the Last 50 Years with the Museum, Old, and Modern Samples.

The pig industry is usually considered an intensive livestock industry, mainly supported by hybrid breeding between commercial pig breeds. However, people's pursuit of a more natural environment and higher meat quality has led to an increasing demand for eco-friendly and diverse pig feeding systems. Therefore, the importance of rearing and conserving local pig breeds is increasing. The Livni pig is a local breed with good adaptability to the environmental and fodder conditions in central Russia. In this study, we aimed to analyze the genetic diversity and population structure of Livni pigs using whole-genome single nucleotide polymorphism (SNP) data. We utilized the Porcine GGP HD BeadChip on genotype samples from old (n = 32, 2004) and modern (n = 32, 2019) populations of Livni pigs. For the museum samples of Livni pigs (n = 3), we extracted DNA from their teeth, performed genomic sequencing, and obtained SNP genotypes from the whole-genome sequences. SNP genotypes of Landrace (n = 32) and Large White (n = 32) pigs were included for comparative analysis. We observed that the allelic richness of Livni pigs was higher than those of Landrace and Large White pigs (AR = 1.775-1.798 vs. 1.703 and 1.668, respectively). The effective population size estimates (NE5 = 108 for Livni pigs, NE5 = 59 for Landrace and Large White pigs) confirmed their genetic diversity tendency. This was further supported by the length and number of runs of homozygosity, as well as the genomic inbreeding coefficient (almost twofold lower in Livni pigs compared to Landrace and Large White pigs). These findings suggest that the Livni pig population exhibits higher genetic diversity and experiences lower selection pressure compared to commercial pig populations. Furthermore, both principal component and network tree analyses demonstrated a clear differentiation between Livni pigs and transboundary commercial pigs. The TreeMix results indicated gene flow from Landrace ancestors to Livni pigs (2019) and from Large White ancestors to Livni pigs (2004), which was consistent with their respective historical breeding backgrounds. The comparative analysis of museum, old, and modern Livni pigs indicated that the modern Livni pig populations have preserved their historical genomic components, suggesting their potential suitability for future design selection programs.

Whole-genome sequences restore the original classification of dabbling ducks (genus Anas).

Anas, is a genus of dabbling ducks and encompasses a considerable number of species, among which some are the progenitors of domestic ducks. However, the taxonomic position of the Anas genus remains uncertain because several of its species, initially categorized as Anas based on morphological characteristics, were subsequently reclassified and grouped with the South American genus Tachyeres, primarily based on analysis of their mitochondrial gene sequences. Here, we constructed a phylogenetic tree using nine of our recently assembled Anas genomes, two Tachyeres genomes, and one Cairina genome that are publicly available. The results showed that the Northern shoveler (Anas clypeata) and Baikal teal (Anas formosa) clustered with the other Anas species at the whole-genome level rather than with the Steamer ducks (genus Tachyeres). Therefore, we propose to restore the original classification of the Anas genus, which includes the Northern shoveler and Baikal teal species, 47 species in total. Moreover, our study unveiled extensive incomplete lineage sorting and an ancient introgression event from Tachyeres to Anas, which has led to notable phylogenetic incongruence within the Anas genome. This ancient introgression event not only supports the theory that Anas originated in South America but also that it played a significant role in shaping the evolutionary trajectory of Anas, including the domestic duck.

Exploration of Genome-Wide Recombination Rate Variation Patterns at Different Scales in Pigs.

Meiotic recombination is a prevalent process in eukaryotic sexual reproduction organisms that plays key roles in genetic diversity, breed selection, and species evolution. However, the recombination events differ across breeds and even within breeds. In this study, we initially computed large-scale population recombination rates of both sexes using approximately 52 K SNP genotypes in a total of 3279 pigs from four different Chinese and Western breeds. We then constructed a high-resolution historical recombination map using approximately 16 million SNPs from a sample of unrelated individuals. Comparative analysis of porcine recombination events from different breeds and at different resolutions revealed the following observations: Firstly, the 1Mb-scale pig recombination maps of the same sex are moderately conserved among different breeds, with the similarity of recombination events between Western pigs and Chinese indigenous pigs being lower than within their respective groups. Secondly, we identified 3861 recombination hotspots in the genome and observed medium- to high-level correlation between historical recombination rates (0.542~0.683) and estimates of meiotic recombination rates. Third, we observed that recombination hotspots are significantly far from the transcription start sites of pig genes, and the silico-predicted PRDM9 zinc finger domain DNA recognition motif is significantly enriched in the regions of recombination hotspots compared to recombination coldspots, highlighting the potential role of PRDM9 in regulating recombination hotspots in pigs. Our study analyzed the variation patterns of the pig recombination map at broad and fine scales, providing a valuable reference for genomic selection breeding and laying a crucial foundation for further understanding the molecular mechanisms of pig genome recombination.

Omics-based construction of regulatory variants can be applied to help decipher pig liver-related traits.

Genetic variants can influence complex traits by altering gene expression through changes to regulatory elements. However, the genetic variants that affect the activity of regulatory elements in pigs are largely unknown, and the extent to which these variants influence gene expression and contribute to the understanding of complex phenotypes remains unclear. Here, we annotate 90,991 high-quality regulatory elements using acetylation of histone H3 on lysine 27 (H3K27ac) ChIP-seq of 292 pig livers. Combined with genome resequencing and RNA-seq data, we identify 28,425 H3K27ac quantitative trait loci (acQTLs) and 12,250 expression quantitative trait loci (eQTLs). Through the allelic imbalance analysis, we validate two causative acQTL variants in independent datasets. We observe substantial sharing of genetic controls between gene expression and H3K27ac, particularly within promoters. We infer that 46% of H3K27ac exhibit a concomitant rather than causative relationship with gene expression. By integrating GWAS, eQTLs, acQTLs, and transcription factor binding prediction, we further demonstrate their application, through metabolites dulcitol, phosphatidylcholine (PC) (16:0/16:0) and published phenotypes, in identifying likely causal variants and genes, and discovering sub-threshold GWAS loci. We provide insight into the relationship between regulatory elements and gene expression, and the genetic foundation for dissecting the molecular mechanism of phenotypes.

Phenotypic correlations of carpal gland diverticular number with production traits and its genome-wide association analysis in multiple pig populations.

Pig carpal glands play crucial roles in territorial recognition, reproductive behavior, and information exchange; however, their effects on production traits and underlying genetic mechanisms remain unclear. In this study, 1028 pigs from six populations were counted for the carpal gland diverticular numbers (CGDNs) on the left (CGDNL) and right (CGDNR) legs, and their carcass and meat quality traits were assessed. The CGDNs were significantly different among the populations, and Licha Black pigs had a lower CGDN than the Bama Xiang breed. It was also significantly different between sexes, with males having more diverticula than females (p ≤ 0.0391). Moreover, the number was asymmetric, with CGDNR being significantly higher than CGDNL. Notably, CGDNs was significantly correlated with each other in phenotype and genetics and with 24-h pH, 24-h meat color score, 24-h marbling score, fat content, moisture content, sodium salt content, and saturated fatty acid content in phenotype. Furthermore, genome-wide association analyses identified seven SNPs in association with CGDNs at a 5% genome-wide significance level, all of which were located in a 1.78-Mb (35.347-37.129 Mb) region on chromosome 1. CNC10010837 and CNC10010840 were the top SNPs: both had an additive effect of 0.789 ± 0.120 on CGDNR with p = 8.31E-10. These findings provide important insights into the functions and underlying genetic mechanisms of swine carpal glands.

IgA nephropathy: gut microbiome regulates the production of hypoglycosilated IgA1via the TLR4 signaling pathway.

BACKGROUND: IgA nephropathy (IgAN) is a major cause of primary glomerulonephritis characterized by mesangial deposits of galactose-deficient IgA1 (Gd-IgA1). Toll-like receptors (TLRs), particularly TLR4 are involved in the pathogenesis of IgAN. The role of gut microbiota on IgAN patients was recently investigated. However, whether gut microbial modifications of Gd-IgA1 through TLR4 play a role in IgAN remains unclear. METHODS: We recruited subjects into four groups, including 48 patients with untreated IgAN, 22 treated IgAN patients (IgANIT), 22 primary membranous nephropathy (MN), and 31 healthy controls (HCs). Fecal samples were collected to analyze changes in gut microbiome. Gd-IgA1 levels, expression of TLR4, B-cell stimulators, and intestinal barrier function were evaluated in all subjects. C57BL/6 mice were treated with a broad-spectrum antibiotic cocktail to deplete the gut microbiota and then gavaged with fecal microbiota transplanted fromclinical subjects of every group. Gd-IgA1 and TLR4 pathway were detected in peripheral blood mononuclear cells (PBMCs) from IgAN and HCs co-incubated with Lipopolysaccharide (LPS) and TLR4 inhibitor. RESULTS: Compared with other three groups, different compositions and decreased diversity demonstrated gut dysbiosis in un-treated IgAN, especially the enrichment of Escherichia -Shigella. Elevated Gd-IgA1 levels were found in un-treated IgAN patients and correlated with gut dysbiosis, TLR4, B-cell stimulators, indexes of intestinal barrier damage, and proinflammatory cytokines. In vivo, mice colonized with gut microbiota from IgAN and IgANIT patients, copied the IgAN phenotype with the activation of TLR4/MyD88/NF-κB pathway, B-cell stimulators in the intestine, and complied with enhanced proinflammatory cytokines. In vitro, LPS activated TLR4/MyD88/NF-κB pathway, B-cell stimulators and proinflammatory cytokines in the PBMCs from IgAN patients, which resulted in overproduction of Gd-IgA1 and inhibited by TLR4 inhibitor. CONCLUSIONS: Our results illustrated that gut-kidney axis was involved in the pathogenesis of IgAN. Gut dysbiosis could stimulate the overproduction of Gd-IgA1 by TLR4 signaling pathway production and B-cell stimulators.

Single-cell profiling of the pig cecum at various developmental stages.

The gastrointestinal tract is essential for food digestion, nutrient absorption, waste elimination, and microbial defense. Single-cell transcriptome profiling of the intestinal tract has greatly enriched our understanding of cellular diversity, functional heterogeneity, and their importance in intestinal tract development and disease. Although such profiling has been extensively conducted in humans and mice, the single-cell gene expression landscape of the pig cecum remains unexplored. Here, single-cell RNA sequencing was performed on 45 572 cells obtained from seven cecal samples in pigs at four different developmental stages (days (D) 30, 42, 150, and 730). Analysis revealed 12 major cell types and 38 subtypes, as well as their distinctive genes, transcription factors, and regulons, many of which were conserved in humans. An increase in the relative proportions of CD8 + T and Granzyme A (low expression) natural killer T cells (GZMA low NKT) cells and a decrease in the relative proportions of epithelial stem cells, Tregs, RHEX + T cells, and plasmacytoid dendritic cells (pDCs) were noted across the developmental stages. Moreover, the post-weaning period exhibited an up-regulation in mitochondrial genes, COX2 and ND2, as well as genes involved in immune activation in multiple cell types. Cell-cell crosstalk analysis indicated that IBP6 + fibroblasts were the main signal senders at D30, whereas IBP6 - fibroblasts assumed this role at the other stages. NKT cells established interactions with epithelial cells and IBP6 + fibroblasts in the D730 cecum through mediation of GZMA-F2RL1/F2RL2 pairs. This study provides valuable insights into cellular heterogeneity and function in the pig cecum at different development stages.

Pig H3K4me3, H3K27ac, and gene expression profiles reveal reproductive tissue-specific activity of transposable elements.

Regulatory sequences and transposable elements (TEs) account for a large proportion of the genomic sequences of species; however, their roles in gene transcription, especially tissue-specific expression, remain largely unknown. Pigs serve as an excellent animal model for studying genomic sequence biology due to the extensive diversity among their wild and domesticated populations. Here, we conducted an integrated analysis using H3K27ac ChIP-seq, H3K4me3 ChIP-seq, and RNA-seq data from 10 different tissues of seven fetuses and eight closely related adult pigs. We aimed to annotate the regulatory elements and TEs to elucidate their associations with histone modifications and mRNA expression across different tissues and developmental stages. Based on correlation analysis between mRNA expression and H3K27ac and H3K4me3 peak activity, results indicated that H3K27ac exhibited stronger associations with gene expression than H3K4me3. Furthermore, 1.45% of TEs overlapped with either the H3K27ac or H3K4me3 peaks, with the majority displaying tissue-specific activity. Notably, a TE subfamily (LTR4C_SS), containing binding motifs for SIX1 and SIX4, showed specific enrichment in the H3K27ac peaks of the adult and fetal ovaries. RNA-seq analysis also revealed widespread expression of TEs in the exons or promoters of genes, including 4 688 TE-containing transcripts with distinct development stage-specific and tissue-specific expression. Of note, 1 967 TE-containing transcripts were enriched in the testes. We identified a long terminal repeat (LTR), MLT1F1, acting as a testis-specific alternative promoter in SRPK2 (a cell cycle-related protein kinase) in our pig dataset. This element was also conserved in humans and mice, suggesting either an ancient integration of TEs in genes specifically expressed in the testes or parallel evolutionary patterns. Collectively, our findings demonstrate that TEs are deeply embedded in the genome and exhibit important tissue-specific biological functions, particularly in the reproductive organs.

Gut microbiota affects the estrus return of sows by regulating the metabolism of sex steroid hormones.

BACKGROUND: Sex hormones play important roles in the estrus return of post-weaning sows. Previous studies have demonstrated a complex and bi-directional regulation between sex hormones and gut microbiota. However, the extent to which the gut microbiota affects estrus return of post-weaning sows is largely unknown. RESULTS: In this study, we first screened 207 fecal samples from well-phenotyped sows by 16S rRNA gene sequencing and identified significant associations between microbes and estrus return of post-weaning sows. Using metagenomic sequencing data from 85 fecal samples, we identified 37 bacterial species that were significantly associated with estrus return. Normally returning sows were characterized by increased abundances of L. reuteri and P. copri and decreased abundances of B. fragilis, S. suis, and B. pseudolongum. The changes in gut microbial composition significantly altered the functional capacity of steroid hormone biosynthesis in the gut microbiome. The results were confirmed in a validation cohort. Significant changes in sex steroid hormones and related compounds were found between normal and non-return sows via metabolome analysis. An integrated analysis of differential bacterial species, metagenome, and fecal metabolome provided evidence that normal return-associated bacterial species L. reuteri and Prevotella spp. participated in the degradation of pregnenolone, progesterone, and testosterone, thereby promoting estrogen biosynthesis. Furthermore, the microbial metabolites related to sow energy and nutrient supply or metabolic disorders also showed relationships with sow estrus return. CONCLUSIONS: An integrated analysis of differentially abundant bacterial species, metagenome, and fecal metabolome revealed the involvement of L. reuteri and Prevotella spp. in sow estrus return. These findings provide deep insight into the role of gut microbiota in the estrus return of post-weaning sows and the complex cross-talk between gut microbiota and sex hormones, suggesting that the manipulation of the gut microbiota could be an effective strategy to improve sow estrus return after weaning.

Metagenomic sequencing reveals swine lung microbial communities and metagenome-assembled genomes associated with lung lesions—a pilot study / La secuenciación metagenómica revela comunidades microbianas de pulmón porcino y genomas ensamblados en metagenoma asociados con lesiones pulmonares: un estudio piloto

Low microbial biomass in the lungs, high host-DNA contamination and sampling difficulty limit the study on lung microbiome. Therefore, little is still known about lung microbial communities and their functions. Here, we perform a preliminary exploratory study to investigate the composition of swine lung microbial community using shotgun metagenomic sequencing and compare the microbial communities between healthy and severe-lesion lungs. We collected ten lavage-fluid samples from swine lungs (five from healthy lungs and five from severe-lesion lungs), and obtained their metagenomes by shotgun metagenomic sequencing. After filtering host genomic DNA contamination (93.5% ± 1.2%) in the lung metagenomic data, we annotated swine lung microbial communities ranging from four domains to 645 species. Compared with previous taxonomic annotation of the same samples by the 16S rRNA gene amplicon sequencing, it annotated the same number of family taxa but more genera and species. We next performed an association analysis between lung microbiome and host lung-lesion phenotype. We found three species (Mycoplasma hyopneumoniae, Ureaplasma diversum, and Mycoplasma hyorhinis) were associated with lung lesions, suggesting they might be the key species causing swine lung lesions. Furthermore, we successfully reconstructed the metagenome-assembled genomes (MAGs) of these three species using metagenomic binning. This pilot study showed us the feasibility and relevant limitations of shotgun metagenomic sequencing for the characterization of swine lung microbiome using lung lavage-fluid samples. The findings provided an enhanced understanding of the swine lung microbiome and its role in maintaining lung health and/or causing lung lesions.(AU)

Single-cell dynamics of liver development in postnatal pigs.

The postnatal development of the liver, an essential organ for metabolism and immunity, remains poorly characterized at the single-cell resolution. Here, we generated single-nucleus and single-cell transcriptomes of 84,824 pig liver cells at four postnatal time points: day 30, 42, 150, and 730. We uncovered 23 cell types, including three rare cell types: plasmacytoid dendritic cells, CAVIN3+IGF2+ endothelial cells, and EBF1+ fibroblasts. The latter two were verified by multiplex immunohistochemistry. Trajectory and gene regulatory analyses revealed 33 genes that encode transcription factors associated with hepatocyte development and function, including NFIL3 involved in regulating hepatic metabolism. We characterized the spatiotemporal heterogeneity of liver endothelial cells, identified and validated leucine zipper protein 2 (LUZP2) as a novel adult liver sinusoidal endothelial cell-specific transcription factor. Lymphoid cells (NK and T cells) governed the immune system of the pig liver since day 30. Furthermore, we identified a cluster of tissue-resident NK cells, which displayed virus defense functions, maintained proliferative features at day 730, and manifested a higher conservative transcription factor expression pattern in humans than in mouse liver. Our study presents the most comprehensive postnatal liver development single-cell atlas and demonstrates the metabolic and immune changes across the four age stages.

[Activation of intestinal mucosal TLR4/NF-κB pathway is associated with renal damage in mice with pseudo-sterile IgA nephropathy].

Objective To investigate the effect of intestinal mucosal Toll-like receptor 4/nuclear factor κB (TLR4/NF-κB) signaling pathway on renal damage in pseudo-sterile IgA nephropathy (IgAN) mice. Methods C57BL/6 mice were randomly divided into experimental group (pseudosterile mouse model group), control group (IgAN mouse model group), pseudosterile mouse blank group, and normal mouse blank group. Pseudosterile mice were established by intragastric administration of quadruple antibiotics once a day for 14 days. The pseudosterile IgAN mouse model was set up by combination of oral bovine serum albumin (BSA) administration and staphylococcal enterotoxin B (SEB) injection. The pathological changes of renal tissue were observed by immunofluorescence staining and PAS staining, and the intestinal mucosa barrier damage indicators lipopolysaccharide(LPS), soluble intercellular adhesion molecule 1(sICAM-1) and D-lactate(D-LAC) were analyzed by ELISA. Biochemical analysis was used to test 24 hour urine protein, serum creatinine and blood urea nitrogen. The mRNA and protein levels of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and nuclear factor κB (NF-κB) were detected by reverse transcription PCR and Western blot analysis. Results The kidney damage of pseudosterile IgAN mice was more severe than that of IgAN mice, and the expressions of intestinal mucosal barrier damage markers (LPS, sICAM-1 and D-LAC) were significantly increased in pseudosterile IgAN mice. In addition, the expressions of TLR4, MyD88, and NF-κB level were all up-regulated in the intestinal tissues of IgAN pseudosterile mice. Conclusion Intestinal flora disturbance leads to intestinal mucosal barrier damage and induces activation of TLR4 signaling pathway to mediate renal injury in IgAN.

Dominance is common in mammals and is associated with trans-acting gene expression and alternative splicing.

BACKGROUND: Dominance and other non-additive genetic effects arise from the interaction between alleles, and historically these phenomena play a major role in quantitative genetics. However, most genome-wide association studies (GWAS) assume alleles act additively. RESULTS: We systematically investigate both dominance-here representing any non-additive within-locus interaction-and additivity across 574 physiological and gene expression traits in three mammalian stocks: F2 intercross pigs, rat heterogeneous stock, and mice heterogeneous stock. Dominance accounts for about one quarter of heritable variance across all physiological traits in all species. Hematological and immunological traits exhibit the highest dominance variance, possibly reflecting balancing selection in response to pathogens. Although most quantitative trait loci (QTLs) are detectable as additive QTLs, we identify 154, 64, and 62 novel dominance QTLs in pigs, rats, and mice respectively that are undetectable as additive QTLs. Similarly, even though most cis-acting expression QTLs are additive, gene expression exhibits a large fraction of dominance variance, and trans-acting eQTLs are enriched for dominance. Genes causal for dominance physiological QTLs are less likely to be physically linked to their QTLs but instead act via trans-acting dominance eQTLs. In addition, thousands of eQTLs are associated with alternatively spliced isoforms with complex additive and dominant architectures in heterogeneous stock rats, suggesting a possible mechanism for dominance. CONCLUSIONS: Although heritability is predominantly additive, many mammalian genetic effects are dominant and likely arise through distinct mechanisms. It is therefore advantageous to consider both additive and dominance effects in GWAS to improve power and uncover causality.

Genetic dissection and genomic prediction for pork cuts and carcass morphology traits in pig.

BACKGROUND: As pre-cut and pre-packaged chilled meat becomes increasingly popular, integrating the carcass-cutting process into the pig industry chain has become a trend. Identifying quantitative trait loci (QTLs) of pork cuts would facilitate the selection of pigs with a higher overall value. However, previous studies solely focused on evaluating the phenotypic and genetic parameters of pork cuts, neglecting the investigation of QTLs influencing these traits. This study involved 17 pork cuts and 12 morphology traits from 2,012 pigs across four populations genotyped using CC1 PorcineSNP50 BeadChips. Our aim was to identify QTLs and evaluate the accuracy of genomic estimated breed values (GEBVs) for pork cuts. RESULTS: We identified 14 QTLs and 112 QTLs for 17 pork cuts by GWAS using haplotype and imputation genotypes, respectively. Specifically, we found that HMGA1, VRTN and BMP2 were associated with body length and weight. Subsequent analysis revealed that HMGA1 primarily affects the size of fore leg bones, VRTN primarily affects the number of vertebrates, and BMP2 primarily affects the length of vertebrae and the size of hind leg bones. The prediction accuracy was defined as the correlation between the adjusted phenotype and GEBVs in the validation population, divided by the square root of the trait's heritability. The prediction accuracy of GEBVs for pork cuts varied from 0.342 to 0.693. Notably, ribs, boneless picnic shoulder, tenderloin, hind leg bones, and scapula bones exhibited prediction accuracies exceeding 0.600. Employing better models, increasing marker density through genotype imputation, and pre-selecting markers significantly improved the prediction accuracy of GEBVs. CONCLUSIONS: We performed the first study to dissect the genetic mechanism of pork cuts and identified a large number of significant QTLs and potential candidate genes. These findings carry significant implications for the breeding of pork cuts through marker-assisted and genomic selection. Additionally, we have constructed the first reference populations for genomic selection of pork cuts in pigs.

Accurate haplotype construction and detection of selection signatures enabled by high quality pig genome sequences.

High-quality whole-genome resequencing in large-scale pig populations with pedigree structure and multiple breeds would enable accurate construction of haplotype and robust selection-signature detection. Here, we sequence 740 pigs, combine with 149 of our previously published resequencing data, retrieve 207 resequencing datasets, and form a panel of worldwide distributed wild boars, aboriginal and highly selected pigs with pedigree structures, amounting to 1096 genomes from 43 breeds. Combining with their haplotype-informative reads and pedigree structure, we accurately construct a panel of 1874 haploid genomes with 41,964,356 genetic variants. We further demonstrate its valuable applications in GWAS by identifying five novel loci for intramuscular fat content, and in genomic selection by increasing the accuracy of estimated breeding value by 36.7%. In evolutionary selection, we detect MUC13 gene under a long-term balancing selection, as well as NPR3 gene under positive selection for pig stature. Our study provides abundant genomic variations for robust selection-signature detection and accurate haplotypes for deciphering complex traits in pigs.

Characterization of the pig lower respiratory tract antibiotic resistome.

Respiratory diseases and its treatments are highly concerned in both the pig industry and human health. However, the composition and distribution of antibiotic resistance genes (ARGs) in swine lower respiratory tract microbiome remain unknown. The relationships of ARGs with mobile genetic elements (MGEs) and lung health are unclear. Here, we characterize antibiotic resistomes of the swine lower respiratory tract microbiome containing 1228 open reading frames belonging to 372 ARGs using 745 metagenomes from 675 experimental pigs. Twelve ARGs conferring resistance to tetracycline are related to an MGE Tn916 family, and multiple types of ARGs are related to a transposase gene tnpA. Most of the linkage complexes between ARGs and MGEs (the Tn916 family and tnpA) are also observed in pig gut microbiomes and human lung microbiomes, suggesting the high risk of these MGEs mediating ARG transfer to both human and pig health. Gammaproteobacteria are the major ARG carriers, within which Escherichia coli harbored >50 ARGs and >10 MGEs. Although the microbial compositions structure the compositions of ARGs, we identify 73 ARGs whose relative abundances are significantly associated with the severity of lung lesions. Our results provide the first overview of ARG profiles in the swine lower respiratory tract microbiome.

Developmental dynamics of the single nucleus regulatory landscape of pig hippocampus.

The hippocampus is a brain region associated with memory, learning and spatial navigation, its aging-related dysfunction is a common sign of Alzheimer's disease. Pig is a good model for human neurodegenerative disease, but our understanding of the regulatory program of the pig hippocampus and its cross-species conservation in humans remains limited. Here, we profiled chromatin accessibility in 33,409 high-quality nuclei and gene expression in 8,122 high-quality nuclei of the pig hippocampus at four postnatal stages. We identified 510,908 accessible chromatin regions (ACRs) in 12 major cell types, among which progenitor cells such as neuroblasts and oligodendrocyte progenitor cells showed a dynamic decrease from early to later developmental stages. We revealed significant enrichment of transposable elements in cell type-specific ACRs, particularly in neuroblasts. We identified oligodendrocytes as the most prominent cell type with the greatest number of genes that showed significant changes during the development. We identified ACRs and key transcription factors underlying the trajectory of neurogenesis (such as POU3F3 and EGR1) and oligodendrocyte differentiation (RXRA and FOXO6). We examined 27 Alzheimer's disease-related genes in our data and found that 15 showed cell type-specific activity (TREM2, RIN3 and CLU), and 15 genes displayed age-associated dynamic activity (BIN1, RABEP1 and APOE). We intersected our data with human genome-wide association study results to detect neurological disease-associated cell types. The present study provides a single nucleus-accessible chromatin landscape of the pig hippocampus at different developmental stages and is helpful for the exploration of pigs as a biomedical model in human neurodegenerative diseases.

Genetic dissection of 26 meat cut, meat quality and carcass traits in four pig populations.

BACKGROUND: Currently, meat cut traits are integrated in pig breeding objectives to gain extra profit. However, little is known about the heritability of meat cut proportions (MCP) and their correlations with other traits. The aims of this study were to assess the heritability and genetic correlation of MCP with carcass and meat quality traits using single nucleotide polymorphism chips and conduct a genome-wide association study (GWAS) to identify candidate genes for MCP. RESULTS: Seventeen MCP, 12 carcass, and seven meat quality traits were measured in 2012 pigs from four populations (Landrace; Yorkshire; Landrace and Yorkshire hybrid pigs; Duroc, and Landrace and Yorkshire hybrid pigs). Estimates of the heritability for MCP ranged from 0.10 to 0.55, with most estimates being moderate to high and highly consistent across populations. In the combined population, the heritability estimates for the proportions of scapula bone, loin, back fat, leg bones, and boneless picnic shoulder were 0.44 ± 0.04, 0.36 ± 0.04, 0.44 ± 0.04, 0.38 ± 0.04, and 0.39 ± 0.04, respectively. Proportion of middle cuts was genetically significantly positively correlated with intramuscular fat content and backfat depth. Proportion of ribs was genetically positively correlated with carcass oblique length and straight length (0.35 ± 0.08 to 0.45 ± 0.07) and negatively correlated with backfat depth (- 0.26 ± 0.10 to - 0.45 ± 0.10). However, weak or nonsignificant genetic correlations were observed between most MCP, indicating their independence. Twenty-eight quantitative trait loci (QTL) for MCP were detected by GWAS, and 24 new candidate genes related to MCP were identified, which are involved with growth, height, and skeletal development. Most importantly, we found that the development of the bones in different parts of the body may be regulated by different genes, among which HMGA1 may be the strongest candidate gene affecting forelimb bone development. Moreover, as previously shown, VRTN is a causal gene affecting vertebra number, and BMP2 may be the strongest candidate gene affecting hindlimb bone development. CONCLUSIONS: Our results indicate that breeding programs for MCP have the potential to enhance carcass composition by increasing the proportion of expensive cuts and decreasing the proportion of inexpensive cuts. Since MCP are post-slaughter traits, the QTL and candidate genes related to these traits can be used for marker-assisted and genomic selection.

Employing pigs to decipher the host genetic effect on gut microbiome: advantages, challenges, and perspectives.

The gut microbiota is a complex and diverse ecosystem comprised of trillions of microbes and plays an essential role in host's immunity, metabolism, and even behaviors. Environmental and host factors drive the huge variations in the gut microbiome among individuals. Here, we summarize accumulated evidences about host genetic effect on the gut microbial compositions with emphases on the correlation between host genetic kinship and the similarity of microbial compositions, heritability estimates of microbial taxa, and identification of genomic variants associated with the gut microbiome in pigs as well as in humans. A proportion of bacterial taxa have been reported to be heritable, and numerous variants associated with the diversity of the gut microbiota or specific taxa have been identified in both humans and pigs. LCT and ABO gene have been replicated in multiple studies, and its mechanism have been elucidated clearly. We also discuss the main advantages and challenges using pigs as experimental animals in exploring host genetic effect on the gut microbial composition and provided our insights on the perspectives in this area.