When healthy, wild-type individuals from closely related species are crossed to each other, the resulting hybrids often display fundamental problems in development. Problems such as hybrid sterility or hybrid inviability can sometimes act as barriers to gene flow between species and are therefore considered to be the stuff of speciation—the process by which one species splits into two (1). These developmental problems are known to manifest from deleterious genetic interactions, known as hybrid incompatibilities, between the two divergent parental genomes (2). The particular phenotype from hybrid crosses can unmask cryptic evolutionary processes that are otherwise not visible in pure species. Understanding the genetic and molecular nature of these incompatibilities can therefore provide fundamental insights into normal developmental processes within species and the origins of reproductive barriers between them. In PNAS, Lu et al. resolve a long-standing mystery about hybrids between Xiphophorus fish hybrids that suffer lethal melanoma (3).

In the 1920s, three independent researchers, Myron Gordon, George Haeussler, and Kurt Kosswig, discovered that hybrids between two distant Xiphophorus fish species, the southern platyfish (Xiphophorus maculatus) and its sister species the green swordtail (Xiphophorus hellerii), develop spontaneous and lethal tumors on the dorsal fin (4⇓–6). X. maculatus exhibits a spotted pigmentation pattern in its dorsal fin (called spotted dorsal, Sd), which is not seen in X. helleri. In F1 hybrids between these species, the Sd pigmentation pattern becomes expanded, with the melanin pattern covering the entire dorsal fin due to melanocyte hyperplasia. These F1 hybrids are fertile, and crossing them to X. hellerii parents produces backcross hybrids in classic Mendelian ratios of 1:2:1. A quarter …

↵¹To whom correspondence may be addressed. Email: nitin.phadnis{at}utah.edu.