Comparative screening identifies lineage-associated divergence in DRD4 in cetaceans

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Abstract

Neuromodulatory pathways, particularly dopaminergic signaling, are thought to play important roles in regulating motivation, learning, and exploratory behavior across vertebrates. Major ecological transitions, such as the shift from terrestrial to fully aquatic environments in cetaceans, may be associated with lineage-specific molecular variation in these systems. However, identifying candidate loci involved in such divergence remains challenging due to the large number of genes contributing to neural function. Here, we conducted a comparative screening of eight genes associated with dopaminergic signaling across selected mammalian lineages, including cetaceans and a phylogenetically distinct terrestrial reference lineage. This exploratory analysis revealed that DRD4 uniquely exhibited patterns consistent with episodic lineage-associated divergence in cetaceans relative to other examined genes. Given the limited taxonomic sampling, these findings do not constitute evidence of adaptive evolution. Instead, they highlight DRD4 as a candidate locus for expanded phylogenetic and functional investigation. This hypothesis-generating study provides a foundation for future analyses incorporating broader taxonomic representation and complementary methodological approaches to evaluate the evolutionary significance of DRD4 variation.

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