Natural Hybridization and Melanoma in Swordtail Fish: Genetic Basis and Selective Mechanisms

Abstract

Understanding how genotype maps to phenotype is critical to understanding how evolution can generate and maintain biological diversity. Hybridization provides a great resource to pinpoint genes of interest, disentangle multivariate effects on fitness, and measure evolutionary change in real time. New mutations arising in diverging species can interact negatively in hybrids, generating what is known as hybrid incompatibilities. A famous example of hybrid in-compatibility comes from distantly related laboratory hybrids between Xiphophorus species that cause malignant melanoma. This study utilizes an ongoing hybridization process in natural conditions in other Xiphophorus species to study the genetic basis and evolutionary persistence of melanoma in the wild.

Xiphophorus birchmanni is polymorphic for a coloration pattern on its caudal fin called spotted caudal (Sc). X. malinche lacks this pattern. X. birchmanni – X. malinche hybrids are also polymorphic regarding Sc and its expression can vary from a few black spots to extremely malignant melanoma. A study of juvenile vs adult Sc frequencies suggests that the phenotype is under natural selection in high incidence hybrid populations and therefore I tested whether sexual selection contributes to its maintenance. Visual mate choice trials showed that neither X. birchmanni nor hybrid females prefer spotted over non-spotted individuals. Future studies should further characterize environmental factors or other traits associated with Sc that might be favored by sexual selection via mate choice or intrasexual competition.

To identify the genetic basis of the trait, I performed a Genome Wide Association Study in a X. birchmanni population and determined that a previously known potent oncogene (xmrk) is responsible for driving the expression of the pattern. This was followed by a population ancestry and admixture mapping study that proposed adgre5 and xmrk as the genes responsible for the hybrid incompatibility causing melanoma. I performed functional cell culture and transgenic experiments to determine that adgre5 acts as a tumor suppressor gene.

As far as I know, this is the only study that combines behavior, genomics and molecular biology techniques in an integrative approach to identify and functionally test a hybrid incompatibility (melanoma) to the single gene level in naturally occurring hybridizing species.