Integrated genomic and transcriptomic analysis reveals candidate genes for Siniperca chuatsi adaptation to formulated diet

Mandarin fish ( Siniperca chuatsi ), a carnivorous species with a strong preference for live prey, exhibits significant inter-individual variation in acceptance of formulated diet during domestication. Following formulated diet domestication via a specific protocol, some individuals readily consume dead fish bait and formulated diet, whereas others persistently reject it even under starvation conditions. Given that genetic factors largely govern this trait, selective breeding based on genetic acceptability represents a key strategy for developing formulated diet-adapted broodstock. This study integrates genomic and transcriptomic analyses to elucidate the genetic mechanisms underlying individual variation in formulated diet feeding behavior. We conducted a genome-wide association study (GWAS) on 213 genotyped individuals (118 formulated diet-accepting individuals, 95 formulated diet-resistant individuals), identifying 18 genetic loci associated with formulated diet adaptation. Transcriptomic sequencing of 54 individuals exhibiting extreme phenotypic divergence in formulated diet acceptance enabled the analysis of differentially expressed genes (DEGs) and weighted gene co-expression network analysis (WGCNA). GWAS identified 181 protein-coding candidate genes potentially regulating formulated diet acceptance. Integration of GWAS, WGCNA, and DEGs analyses revealed 30 overlapping candidate genes. Furthermore, these candidate genes were significantly enriched in key signaling pathways (e.g., PI3K-Akt, cAMP, Rap1) and nervous system functions (e.g., cholinergic synapse, long-term depression). Notably, PRMT7 , MT2 , POLR3B , MAP2K1 , APPL2 , GNAO1A , LOC122875534 (LEPTIN-like), and LOC122874706 (muscarinic acetylcholine receptor M2-like) emerged as the most promising candidate genes influencing formulated diet acceptance. This research provides novel insights into the regulatory mechanisms governing formulated diet acceptance in mandarin fish, offering valuable information for designing effective management and selective breeding programs. • Integration of GWAS, DEGs, and WGCNA revealed candidate genes for the formulated diet adaptation trait. • Reveals novel hepatic roles of MT2 , MAP2K1 , and GNAO1A in diet adaptation via metabolic reprogramming and a liver-brain axis. • Supplies genomic targets for selective breeding of formulated diet-adapted mandarin fish, enhancing aquaculture efficiency.