Litter size is one of the most important economic traits for pig production as it is directly related to the production efficiency. Litter size is affected by interactions between multiple genes and the environment. While recent studies have identified some genes associated with prolificacy in pigs, transcriptomic studies of specific genes affecting litter size in porcine ovaries are rare. In order to identify candidate genes associated with litter size in swine, we assessed gene expression differences between the ovaries of Yorkshire pigs with extremely high and low litter sizes using the RNA-Seq method. A total of 1 243 differentially expressed genes were identified: 897 genes were upregulated and 346 genes were downregulated in high litter size ovary samples compared with low litter size ovary samples. A large number of these genes related to steroid hormone regulation in animal ovaries, including 59 Gene Ontology terms and 27 Kyoto Encyclopedia of Genes and Genomes pathways involved in steroid biosynthesis and ovarian steroidogenesis. From these differentially expressed genes, we identified a total of 11 genes using a bioinformatics screen that may be associated with high litter size in Yorkshire pigs. These results provide a list of new candidate genes for porcine litter size and prolificacy to be further investigated.

Copy number variations (CNVs) confer significant effects on genetic innovation and phenotypic variation. Previous CNV studies in swine seldom focused on in-depth characterization of global CNVs. Using whole-genome assembly comparison (WGAC) and whole-genome shotgun sequence detection (WSSD) approaches by next generation sequencing (NGS), we probed formation signatures of both segmental duplications (SDs) and individualized CNVs in an integrated fashion, building the finest resolution CNV and SD maps of pigs so far. We obtained copy number estimates of all protein-coding genes with copy number variation carried by individuals, and further confirmed two genes with high copy numbers in Meishan pigs through an enlarged population. We determined genome-wide CNV hotspots, which were significantly enriched in SD regions, suggesting evolution of CNV hotspots may be affected by ancestral SDs. Through systematically enrichment analyses based on simulations and bioinformatics analyses, we revealed CNV-related genes undergo a different selective constraint from those CNV-unrelated regions, and CNVs may be associated with or affect pig health and production performance under recent selection. Our studies lay out one way for characterization of CNVs in the pig genome, provide insight into the pig genome variation and prompt CNV mechanisms studies when using pigs as biomedical models for human diseases.

Identification of genomic signatures of selection that help reveal genetic mechanisms underlying traits in domesticated pigs is of importance. Anqing six-end-white pig (ASP), a representative of the native breeds in China, has many distinguishing phenotypic characteristics. To identify the genomic signatures of selection of the ASP, whole-genome sequencing of 20 ASPs produced 469.01 Gb of sequence data and more than 26 million single-nucleotide polymorphisms. Combining these data with the available whole genomes of 13 Chinese wild boars, 157 selected regions harboring 48 protein-coding genes were identified by applying the polymorphism levels (θπ) and genetic differentiation (F_ST) based cross approaches. The genes found to be positively selected in ASP are involved in crucial biological processes such as coat color (MC1R), salivary secretion (STATH), reproduction (SPIRE2, OSBP2, LIMK2, FANCA, and CABS1), olfactory transduction (OR5K4), and growth (NPY1R, NPY5R, and SELENOM). Our research increased the knowledge of ASP phenotype-related genes and help to improve our understanding of the underlying biological mechanisms and provide valuable genetic resources that enable effective use of pigs in agricultural production.

Beyond its well-established role in diabetes management, metformin has gained attention as a promising therapeutic for inflammation-related diseases, largely due to its antioxidant capabilities. However, the mechanistic underpinnings of this effect remain elusive. Using in vivo zebrafish models of inflammation, we explored the impact of metformin on neutrophil recruitment and the underlying mechanisms involved. Our data indicate that metformin reduces histone (H3K18) lactylation, leading to the decreased production of reactive oxygen species (ROS) and a muted neutrophil response to both caudal fin injury and otic vesicle inflammation. To investigate the precise mechanisms through which metformin modulates neutrophil migration via ROS and H3K18 lactylation, we meticulously established the correlation between metformin-induced suppression of H3K18 lactylation and ROS levels. Through supplementary experiments involving the restoration of lactate and ROS, our findings demonstrated that elevated levels of both lactate and ROS significantly promoted the inflammatory response in zebrafish. Collectively, our study illuminates previously unexplored avenues of metformin’s antioxidant and anti-inflammatory actions through the downregulation of H3K18 lactylation and ROS production, highlighting the crucial role of epigenetic regulation in inflammation and pointing to metformin’s potential in treating inflammation-associated conditions.