The whole genome duplication that occurred in ray-finned fish coincided with the radiation of teleost species; consequently, these two phenomena have often been linked. Using the Tetraodon and zebrafish complete genome sequences, we tested a molecular hypothesis that can relate whole genome duplication to speciation in teleosts. We estimate that thousands of genes that remained duplicated when Tetraodon and zebrafish diverged underwent reciprocal loss subsequently in these two species, probably contributing to reproductive isolation between them.