Natural hybridization reveals incompatible alleles that cause melanoma in swordtail fish

The establishment of reproductive barriers between populations is the key process that fuels the evolution of new species. A genetic framework for this process was proposed over 80 years ago, which posits "incompatible" interactions between genes that result in reduced survival or reproduction in hybrids. Despite this foundational work, progress has been slow in identifying individual genes that underlie hybrid incompatibilities, with only a handful known to date. Here, we use a combination of approaches to precisely map the genes that drive the development of a melanoma incompatibility in swordtail fish hybrids. We find that one of the genes involved in this incompatibility also causes melanoma in hybrids between distantly related species. Moreover, we show that this melanoma reduces survival in the wild, likely due to progressive degradation of the fin. Together, this work represents only the second case where the genes underlying a vertebrate hybrid incompatibility have been identified and provides the first glimpse into the action of these genes in natural hybrid populations. One sentence summaryUsing a combination of mapping approaches, we identify interacting genes that lead to melanoma in hybrids and characterize their effects in natural hybrid populations.