Novel alternative splicing associated with feed efficiency in dairy cattle under distinct diet compositions

Feed efficiency (FE) in dairy cattle is influenced by both genetic and environmental factors, including diet composition. Differential expression (DE) of mRNA isoforms was analyzed using publicly available RNA-Seq data to investigate alternative splicing associated with residual feed intake (RFI) under control and High-Concentrate (HC) diets in Holstein and Jersey cattle. Low-RFI (efficient) animals exhibited more extensive transcriptomic responses than their high-RFI counterparts (207 vs. 103 DE isoforms in Holstein; 183 vs. 90 in Jersey), reflecting greater isoform-specific regulation. Under the control diet, DE isoforms were enriched for transcriptional regulation and cellular function pathways, while the HC diet showed a balanced pattern of up- and downregulation affecting growth, signaling, and metabolic pathways. Overlap between DE isoforms and milk production QTLs was characterized based on functional annotations. In Holsteins, overlap decreased from 66.87% under control to 49.69% under HC, while in Jersey, it increased from 45.02% under control to 64.64% under HC. Comparison between low- and high-RFI animals showed a reduction in reproductive QTL overlap in both breeds: Holstein decreased from 29.65% to 18.69%, respectively, and Jersey decreased from 13.27% to 3.50%, respectively. In Holsteins, the mRNA isoforms WDR33_6 and PRKAR2A_3 were identified as DE transcripts associated with dietary treatment and RFI status suggesting potential roles in FE and metabolic adaptation. As an exploratory study, these results indicate mRNA isoform-level differences associated with RFI and dietary responses in Holstein and Jersey cattle. The observed patterns may reflect contrasts between reproductive and milk production-related biological processes, providing initial insights into candidate features associated with productivity and sustainability.