The repeated evolution of hybrid melanoma across Xiphophorus fish - Project Summary Modern genome sequencing has shown that many species exchange genes with their close relatives through a process known as hybridization. As a result, the genomes of modern species are a mosaic of regions derived from past hybridization. Because of this, many species including our own must contend with the potentially negative consequences that can arise from mixing two divergent genomes. One of these negative consequences is the exposure of “hybrid incompatibilities” or genes that do not interact properly in hybrids. Uncovering the evolutionary forces that drive the formation of these hybrid incompatibilities is crucial to understanding how the genomes of modern species function. Although this is an important question, we have rarely been able to identify the genetic architecture of hybrid incompatibilities in vertebrates and lack the empirical data needed to understand what predisposes certain genes or genomic regions to negative interactions in hybrids. My postdoctoral research will investigate the evolution of a repeatedly evolved hybrid incompatibility in fish species where hybrid offspring from multiple crosses develop melanoma. I will combine classical genetic crosses, population genomics, and state-of-the-art functional genomic techniques to generate a comprehensive model of how hybrid incompatibilities evolve. In Aim 1, I will perform multiple genetic mapping crosses to identify genomic regions that drive hybrid melanoma. In Aim 2, I will characterize structural variation in the genome and its functional consequences on pigmentation genes involved in hybrid melanoma. Finally, in Aim 3, I will complement this work with a comparative genomic and transcriptomic approach to investigate how genes controlling pigmentation function within gene regulatory networks and become disrupted in hybrids with melanoma. Together, these approaches will give us unprecedented insights into how hybridization has shaped our genomes and the repeated origin of an evolutionarily and biomedically important phenotype. My primary goal under this NRSA F32 fellowship is to receive the scientific and professional training I need to establish my own independent research lab that unites molecular and computational biology with cutting-edge genomic approaches to establish models for how evolutionary processes shape genome content and function. As a postdoctoral fellow in the Schumer and Petrov labs at Stanford University, I will receive training in cutting-edge genomic techniques and analytical approaches. In addition to my scientific training, I will strengthen the professional skills needed to establish my future lab including grantsmanship, network building, and mentorship. In sum, with the training I will receive under this fellowship, I will be poised to lead a research program with great power to link molecular mechanisms to evolutionary outcomes and connect genotypes to phenotypes at the molecular and organismal level.
