PSI-2 Molecular mechanisms regulating feed efficiency and muscle growth in beef cattle

Abstract Animals with greater feed efficiency use fewer resources to produce skeletal muscle, the primary product in beef production. As muscle represents approximately 50% of BW in beef cattle, efficient utilization of feed is interconnected with growth. However, little is known about molecular pathways interconnecting these two components of production. The overall objective of the study was to determine relationships between feed efficiency and growth at the molecular level in skeletal muscle of beef cattle. The specific objective of this study was to identify genes and pathways that are associated with variation in ADG, as an index of growth. We hypothesize that increased expression of genes involved in energy utilization are associated with greater ADG. Angus steers (n = 100) were enrolled in 70-d feed efficiency trials using the Vytelle GrowSafe 8000 individual feed intake monitoring system. Muscle samples (~ 500 ug) were collected via needle biopsy from the wing of the ileum between the axis and transverse processes of the lumbar vertebrae during the last 30 d of the trial. Samples were snap-frozen in liquid nitrogen and stored at -80°C. Frozen tissue was pulverized and RNA extracted from ~ 50mg/sample using a commercial kit (zymoresearch.com). Quality was verified using Agilent 4200 Tapestation (agilent.com). Libraries were constructed using SMART Seq v4 3’ DE Kit. Libraries were assessed for quality and quantity, and subsequently pooled for sequencing using a Novaseq 6000 (illumina.com). STAR RNA-seq aligner was used to map the reads to the bovine genome (ARS-UCD_2.0). Animals were ranked according to ADG and grouped by 20th percentile; the first, third, and fifth groups were designated as “Very Low”, “Medium”, and “Very High”, respectively. Expression profiles between the groups were compared using DESeq2 in R (version 3.5). A total of 1,199 genes were identified as differentially expressed (fdr P-value < 0.05). Gene sets were functionally annotated using Database for Annotation, Visualization and Integrated Discovery (david.ncifcrf.gov). Genes expressed at greater levels in Very High ADG steers were significantly enriched (fdr P -value < 0.05) in Gene Ontology(GO) functions related to cellular metabolism (226 of 1199 genes). In addition, 92 genes in this set were associated with the KEGG pathway for VEGF/VEGFR-2 signaling, which regulates angiogenesis and has been associated with muscle growth. Genes expressed at greater levels in Very Low ADG steers were significantly enriched in GO terms related to proteasome degradation and mitophagy, both of which have been associated with muscle loss. In conclusion, these results support that variation in cellular metabolism contributes to variation in muscle growth, as reflected by ADG. They also highlight angiogenesis as a pathway that is worthy of further investigation for its role in beef cattle production.