Currently, mouse khdrbs genes were found expressed primarily in the brain, differing from that of the invertebrate orthologs, and khdrbs KO mice exhibited brain defects, indicating that khdrbs genes may be in the genetic toolkit correlated to vertebrate brain development (Ehrmann et al., 2013). In invertebrates, khdrbs genes were found expressed specifically in germ line (Lee and Schedl, 2001; Ding et al., 2010), so as zebrafish khdrbs1a, which was also expressed in the gonad primordium. Thus we surmise that one of the functions about khdrbs genes is to regulate gonad genesis. In addition to expression in gonads, zebrafish khdrbs genes were also found expressed in new domains such as the substructures of brain, especially in telencephalon. Telencephalon is an utterly vertebrate innovation (Murakami et al., 2005; Šestak and Domazet-Lošo, 2015). Considering that KHDRBS proteins act as splicing regulator molecules to control alternative splicing, and the brains have the largest amount of alternative splicing in the body, this distinct expression pattern of khdrbs genes gives a hint that the duplicated khdrbs genes were co-opted for motivating the evolutionary origin of vertebrate brain. Further studies on the expression and functions of khdrbs genes in other representative species within vertebrate lineage will better clarify the roles of KHDRBS played in brain evolution.