Investigation of de novo unique differentially expressed genes related to evolution in exercise response during domestication in Thoroughbred race horses.
Authors: Park Woncheoul, Kim Jaemin, Kim Hyeon Jeong, Choi JaeYoung, Park Jeong-Woong, Cho Hyun-Woo, Kim Byeong-Woo, Park Myung Hum, Shin Teak-Soon, Cho Seong-Keun, Park Jun-Kyu, Kim Heebal, Hwang Jae Yeon, Lee Chang-Kyu, Lee Hak-Kyo, Cho Seoae, Cho Byung-Wook
Journal: PloS one
Summary
# Editorial Summary Researchers used de novo RNA sequencing analysis—which identifies genetic variants without relying on a reference genome—to uncover exercise-responsive genes in six Thoroughbreds sampled before and after exertion, identifying 1,034 previously undetected differentially expressed genes in skeletal muscle and 567 in blood. By cross-referencing these novel genes with evolutionary selection data from whole genome re-sequencing, the team discovered that five genes (TIMELESS, EIF4A3, ZNF592, CHMP4C and FOXO3) showed dual significance: they responded to exercise whilst also bearing signatures of artificial selection during Thoroughbred domestication. Skeletal muscle genes clustered around immune response, stress signalling, and cellular death pathways—key mechanisms in exercise adaptation—with particular enrichment in JAK-STAT and MAPK signalling cascades known to regulate muscle remodelling. Notably, Thoroughbreds exhibited lower genetic diversity at three of these exercise-related loci (CHMP4C, EIF4A3 and FOXO3) compared with Jeju ponies, suggesting intense artificial selection has fixed beneficial variants for athletic performance. These findings refine our understanding of how centuries of selective breeding have shaped the molecular basis of exercise capacity, offering potential biomarkers for identifying genetic predisposition to athletic traits and informing both breeding decisions and targeted conditioning programmes.
Read the full abstract on PubMed
Practical Takeaways
- •Genetic variation in exercise response genes (particularly FOXO3, CHMP4C, EIF4A3) may be markers for individual differences in athletic capacity and stress resilience in racing horses
- •Understanding domestication-selected genes provides insight into why Thoroughbreds have evolved specialized exercise physiology distinct from unselected horse populations
- •Future genetic screening could potentially identify horses predisposed to exercise-related immune or inflammatory complications based on variants in these pathway genes
Key Findings
- •1,034 de novo unique differentially expressed genes (DUDEGs) identified in skeletal muscle and 567 in blood in response to exercise in Thoroughbreds
- •Muscle DUDEGs significantly enriched in immune response, stress response, and apoptosis pathways, with JAK-STAT and MAPK signaling pathway involvement
- •CHMP4C, EIF4A3, and FOXO3 genes identified as both exercise-responsive and under positive selection during Thoroughbred domestication
- •Thoroughbreds showed lower nucleotide diversity in three exercise-related genes compared to Jeju ponies, indicating selective breeding for exercise capacity