Lateralized Gene Splicing in the Brain is Associated With Lateralized Feeding Behavior in an Asymmetrical Scale-eating Cichlid Fish.

Lateralized behavior ("handedness") is a trait observed across all vertebrates, including humans. As an adaptive trait involved in both intraspecific and interspecific interactions, it holds broad evolutionary significance. However, the molecular basis of its brain regulation-particularly post-transcriptional regulation-remains poorly understood. Perissodus microlepis, a textbook example in evolutionary biology and an endemic scale-eating cichlid fish from Lake Tanganyika, displays pronounced lateralized feeding behavior that is complemented by its asymmetric head, by which it bites the scales preferentially from only one side or the other side of its prey. Based on data from two previous studies, we investigated the patterns of alternative splicing-an important yet understudied regulatory mechanism-across multiple brain regions in both resting and predatory states of L-eft or the R-ight morphs of this species. We found that the telencephalon, the cognitive center of the vertebrate brain, shows enrichment in functions related to microtubule and neural development in both states. Compared to the resting state, brain regions in the predatory state exhibited more consistent functional profiles, exhibiting pronounced enrichment in the nervous system. We identified several genes whose proportion of alternatively spliced transcripts was strongly correlated with behavioral laterality, establishing a potentially causal link between alternative splicing and handedness. Our findings underscore the significant role of alternative splicing in important adaptive traits, such as lateralized behavior and present a set of candidate genes for further investigation.