Hepatic transcriptomic signatures associated with divergent residual average daily gain phenotypes in beef steers

This study employed hepatic transcriptional changes to catalogue signature genes associated with divergent residual average daily gain (RADG) phenotypes in crossbred beef steers. A total of 108 crossbred beef steers (average body weight = 495 ± 32kg) were fed a high-forage total mixed ration for 49 d in five dry-lot pens equipped with GrowSafe8000 intake nodes to determine RADG. Steers were ranked based on RADG coefficients, and liver biopsies were collected under local anesthesia from the most efficient (positive RADG; n = 8; 0.73 kg/d) and least efficient (negative RADG; n = 8; −0.69 kg/d) animals. Differential gene expression analysis identified a total of 16,735 genes, based on FDR ≤ 0.05 and an absolute log 2 fold change (|log 2 FC|) ≥ 1.0, 6 genes were upregulated in positive-RADG steers, including COL2A1 , IL32, FBLN2 and MR1 , while 9 genes, including SMO , ABCB4 and RPS3A were downregulated. Gene Ontology enrichment indicated that positive RADG steers exhibited over-representation of biological processes related to regulation of extrinsic apoptotic signaling, DNA-dependent DNA replication, signal transduction in the absence of ligand, and transmembrane transport. Enriched cellular components included the sarcolemma, while enriched molecular functions were associated with carbohydrate transmembrane transporter activity, monosaccharide binding, and antioxidant activity. In contrast, negative RADG steers showed enrichment of biological processes related to immune activation, stress responsiveness, and regulation of ossification. Gene Ontology gene network analysis highlighted COL2A1 , E2F8 , SLC2A5 , and GZMA as highly connected nodes within interaction networks derived from DEGs in positive RADG steers. Pathway enrichment analysis further identified pathways associated with protein digestion and absorption, cytoskeletal organization in muscle cells, and carbohydrate digestion and absorption as over-represented in positive RADG steers. Collectively, these findings describe hepatic transcriptional signatures associated with divergent RADG phenotypes and provide candidate genes and pathways for future studies aimed at functionally validating mechanisms underlying feed efficiency in beef cattle.