Overcoming fishmeal dependence is crucial for the sustainable development of Penaeus vannamei aquaculture, yet the molecular mechanisms underlying the efficient utilization of plant-based diets remain poorly understood. In this study, residual feed intake (RFI) was used as an indicator to investigate these mechanisms. Transcriptome sequencing of the intestine, hepatopancreas, and muscle was performed on shrimp fed a plant-based diet, followed by weighted gene co-expression network analysis (WGCNA) and validation in an independent population. Phenotypic analysis revealed extensive variation in growth performance and RFI among individuals fed the plant-based diet. WGCNA identified four tissue-specific modules significantly associated with RFI, from which 20 hub genes were screened. Independent validation confirmed that seven genes were significantly differentially expressed between high- and low-feed-efficiency groups (q < 0.1): five in the intestine (LOC113811628, LOC113811631, LOC113824170, LOC113817752, LOC113811632) and two in the hepatopancreas (LOC113809216, LOC113820990). These genes are involved in mitochondrial function, energy metabolism, intracellular pH homeostasis, and nucleic acid metabolism, suggesting potential coordination between the intestine and hepatopancreas in response to plant-based diets. Collectively, these findings provide insights into the genetic basis of shrimp adaptation to plant-based diets and offer candidate molecular targets that may inform selective breeding efforts aimed at improving feed efficiency in P. vannamei.
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