The aim of this study is thus to answer this question by taking advantage of the zebrafish (Danio rerio) model, which has a brain resembling that of humans in both basic structures and functional capacities (Tropepe and Sive, 2003). We first analyzed the molecular evolution of khdrbs gene family in representative metazoan taxa, and then examined the expression patterns of khdrbs during early development and in adulthood of zebrafish. We found that khdrbs gene family was expanded by WGD in zebrafish, and all zebrafish khdrbs genes were predominantly expressed in the substructures of brain during early development. Given that these substructures are vertebrate-specific trait, the distinct expression domains of khdrbs genes in zebrafish suggested that khdrbs gene family was co-opted for vertebrate brain development after WGD events around the split of Vertebrata.