We report the sequencing at 131× coverage, de novo assembly and analyses of the genome of a female Tibetan wild boar. We also resequenced the whole genomes of 30 Tibetan wild boars from six major distributed locations and 18 geographically related pigs in China. We characterized genetic diversity, population structure and patterns of evolution. We searched for genomic regions under selection, which includes genes that are involved in hypoxia, olfaction, energy metabolism and drug response. Comparing the genome of Tibetan wild boar with those of neighboring Chinese domestic pigs further showed the impact of thousands of years of artificial selection and different signatures of selection in wild boar and domestic pig. We also report genetic adaptations in Tibetan wild boar that are associated with high altitudes and characterize the genetic basis of increased salivation in domestic pig.

It is evident that epigenetic factors, especially DnA methylation, have essential roles in obesity development. Here, using pig as a model, we investigate the systematic association between DnA methylation and obesity. We sample eight variant adipose and two distinct skeletal muscle tissues from three pig breeds living within comparable environments but displaying distinct fat level. We generate 1,381 Gb of sequence data from 180 methylated DnA immunoprecipitation libraries, and provide a genome-wide DnA methylation map as well as a gene expression map for adipose and muscle studies. The analysis shows global similarity and difference among breeds, sexes and anatomic locations, and identifies the differentially methylated regions. The differentially methylated regions in promoters are highly associated with obesity development via expression repression of both known obesity-related genes and novel genes. This comprehensive map provides a solid basis for exploring epigenetic mechanisms of adipose deposition and muscle growth.

Uncovering genetic variation through resequencing is limited by the fact that only sequences with similarity to the reference genome are examined. Reference genomes are often incomplete and cannot represent the full range of genetic diversity as a result of geographical divergence and independent demographic events. To more comprehensively characterize genetic variation of pigs (Sus scrofa), we generated de novo assemblies of nine geographically and phenotypically representative pigs from Eurasia. By comparing them to the reference pig assembly, we uncovered a substantial number of novel SNPs and structural variants, as well as 137.02-Mb sequences harboring 1737 protein-coding genes that were absent in the reference assembly, revealing variants left by selection. Our results illustrate the power of whole-genome de novo sequencing relative to resequencing and provide valuable genetic resources that enable effective use of pigs in both agricultural production and biomedical research.

A comprehensive transcriptomic survey of pigs can provide a mechanistic understanding of tissue specialization processes underlying economically valuable traits and accelerate their use as a biomedical model. Here we characterize four transcript types (lncRNAs, TUCPs, miRNAs, and circRNAs) and protein-coding genes in 31 adult pig tissues and two cell lines. We uncover the transcriptomic variability among 47 skeletal muscles, and six adipose depots linked to their different origins, metabolism, cell composition, physical activity, and mitochondrial pathways. We perform comparative analysis of the transcriptomes of seven tissues from pigs and nine other vertebrates to reveal that evolutionary divergence in transcription potentially contributes to lineage-specific biology. Long-range promoter–enhancer interaction analysis in subcutaneous adipose tissues across species suggests evolutionarily stable transcription patterns likely attributable to redundant enhancers buffering gene expression patterns against perturbations, thereby conferring robustness during speciation. This study can facilitate adoption of the pig as a biomedical model for human biology and disease and uncovers the molecular bases of valuable traits.

Obesity is a major driver of metabolic diseases such as nonalcoholic fatty liver disease, certain cancers, and insulin resistance. However, there are no effective drugs to treat obesity. Betaine is a nontoxic, chemically stable and naturally occurring molecule. This study shows that dietary betaine supplementation significantly inhibits the white fat production in a high-fat diet (HFD)-induced obese mice. This might be due to betaine preventing the formation of new white fat (WAT), and guiding the original WAT to burn through stimulated mitochondrial biogenesis and promoting browning of WAT. Furthermore, dietary betaine supplementation decreases intramyocellular lipid accumulation in HFD-induced obese mice. Further analysis shows that betaine supplementation reduced intramyocellular lipid accumulation might be associated with increasing polyunsaturated fatty acids (PUFA), fatty acid oxidation, and the inhibition of fatty acid synthesis in muscle. Notably, by performing insulin-tolerance tests (ITTs) and glucose-tolerance tests (GTTs), dietary betaine supplementation could be observed for improvement of obesity and non-obesity induced insulin resistance. Together, these findings could suggest that inhibiting WAT production, intramyocellular lipid accumulation and inflammation, betaine supplementation limits HFD-induced obesity and improves insulin resistance.