Mixing genomes of different species by hybridization can disrupt species-specific genetic interactions that were adapted and fixed within each species population. Such disruption can predispose the hybrids to abnormalities and disease that decrease the overall fitness of the hybrids, and is therefore named as hybrid incompatibility. Interspecies hybridization between southern platyfish and green swordtail fish leads to lethal melanocyte tumorigenesis occurs in hybrids with tumor incidence following Mendelian distributions, suggesting melanoma development is a result of hybrid incompatibility. Such observation represents one of the only two examples exhibiting hybrid incompatibility in vertebrates. One of the two interacting loci has been characterized as a mutant epidermal growth factor receptor. However, the other locus has not been identified despite over 5 decades of active research. This study aims to characterize this regulatory locus.