Comparative brain transcriptomics reveals neural regulatory networks underlying heterosis in crucian carp hybrids

Hybridization is a powerful evolutionary force for genetic improvement, conferring growth advantages and enhanced disease resistance. However, molecular basis of heterosis, especially when mediated by brain-derived neural regulation, remains unclear. To elucidate this, comparative brain transcriptome analysis was performed on red crucian carp, white crucian carp, their hybrid WR, and the backcross-improved WR-II. Our results revealed significant transcriptional changes between parents and their hybrids, leading to the identification of widespread differentially expressed genes (DEGs). Hierarchical clustering and quantitative mid-parent value analysis of DEGs revealed additive expression patterns in WR, whereas WR-II exhibited maternal bias in expression patterns. These DEGs were significantly enriched in pathways related to immune response, neural development, synaptic signaling, and insulin regulation. Weighted gene co-expression network analysis identified eight modules; one module significantly correlated with WR-II (r > 0.5, p < 0.01) contained the highest number of hub genes, totaling 71 (absolute kME value > 0.9). Protein-protein interaction network further highlighted key hub genes in WR-II, including NeuroD1, Rims2, KCND3, Gpc3, and MAPK13, exhibiting above the higher parent expression compared to parents. The encoded proteins form integrated networks central to insulin synthesis and secretion, neuronal excitability, growth regulation, and immune modulation. These findings provide new insights into neural mechanisms that contribute to heterosis in fish.