Multi-omics characterization identifies conserved candidate gene and reveals breed-specific regulatory mechanisms...

Average daily gain (ADG), age at 115 kg (AGE), backfat thickness (BF), and loin eye area (LEA) are key growth and carcass traits in pigs. However, breed-specific molecular regulatory mechanisms underlying these traits remain largely unknown. Here, we identified multiple candidate genes associated with these 4 traits from Duroc and Yorkshire pigs by three Genome-wide association study(GWAS) methods (MLM, FarmCPU, and BLINK) and differential genes expression analysis, verified them based on RNA sequencing(RNA-seq), Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq), and Chromatin Immunoprecipitation sequencing (ChIP-seq) data from Duroc and Yorkshire pigs, and explored the regulatory mechanisms underlying these traits.

GWAS across Duroc, Landrace, and Yorkshire identified 44 high-confidence SNPs. A total of 24, 13, and 19 candidate genes were identified respectively from Duroc, Landrace, and Yorkshire by GWAS and differential gene expression analysis (in three breeds versus Meishan pigs). The candidate gene ARL8A was found to be highly conserved between Duroc and Yorkshire. GeneMANIA networks of Landrace exhibited tightly connected core modules of candidate genes. Integrated RNA-seq, ATAC-seq, and ChIP-seq analyses of muscle and fat tissue data consistently suggested that ARL8A exhibits relatively high transcriptional activity and chromatin accessibility, supporting its potential role in muscle and fat development.

The integration of three GWAS methods with differential gene expression analysis revealed that core candidate genes involved were mainly involved in regulating fat deposition, energy metabolism, and cell growth in constructed breed-specific regulatory networks. Among these candidate genes, ARL8A was a highly conserved gene modulating growth-related traits (BF and LEA), as evidenced by the multi-omics data. Our findings provide an insight into genetic architecture and regulation mechanisms underlying pig growth and development, offering important resources for porcine molecular breeding and genetic improvement.