Identifying candidate genes associated with high utilization of fishmeal-free low-protein diet via integrated GWAS and transcriptome analysis in yellow catfish Tachysurus fulvidraco

The limited supply of key protein ingredients such as fishmeal and soybean meal critically constrains the sustainable development of global aquaculture. While feed formulation technologies have made considerable progress over past decades in alleviating this constraint, genetic improvement through selective breeding remains largely unexplored. In this study, we used the omnivorous yellow catfish as a model to investigate the physiological and genetic adaptations of an all-female population to a fishmeal-free low-protein diet, with the aim of breeding varieties with improved feed conversion efficiency. Individuals were tracked using passive integrated transponder (PIT) tags across two dietary regimes: a commercial diet (CD) containing 42.6% protein and 30.6% fishmeal, and a fishmeal-free low-protein diet (LD) with 38.1% protein and 0% fishmeal. After 16 weeks, the mean body weight of the LD group (23.03 g) was significantly lower than that of the CD group (25.24 g) ( P < 0.05). Genome-wide association analysis (GWAS) of weight gain rate (WGR) in the LD group identified 32 SNPs significantly associated with LD utilization, among which 12 were clustered on chromosome 16. Integrated analysis of GWAS and RNA-seq revealed eight overlapping genes— polr3b , klhl35 , ttc38 , mapk12a , clec20a , ccdc78 , cd22 , and LOC113649797 —enriched in pathways related to “carbohydrate binding” and “serine protein kinase activity”. Notably, a significant intronic SNP within clec20a was associated with WGR variation: homozygous mutant individuals (TT, n = 21) exhibited a markedly higher mean WGR (67.0%) than wild-type individuals (GG, n = 133, 45.2%). Haplotype analysis of clec20a identified five haplotypes, with Hap.02 exhibiting the highest mean WGR. Strikingly, the high-WGR phenotype (≥100%) was exclusively observed in Hap.02 carriers. These findings underscore the functional importance of clec20a in LD adaptation. This study establishes a molecular breeding foundation for improving feed efficiency of fishmeal-free low-protein diet in yellow catfish, supporting sustainable aquaculture through reduced reliance on conventional protein sources. • We conducted the first genome-wide association study (GWAS) and genomic prediction of low-nutrition-level feed utilization—a fishmeal-free, low-protein diet (LD)—in yellow catfish. • Our analysis identified 32 SNPs significantly associated with weight gain rate under the LD, 12 of which were notably clustered on chromosome 16. • Integrated GWAS and RNA-seq analysis revealed eight overlapping genes, among which clec20a emerged as a high-potential candidate, highlighting its functional importance in LD adaptation.