Project summary Due to advances in genome sequencing, researchers have discovered that hybridization, or genetic exchange between species, is widespread. Research over the past decade has demonstrated that hybridization is an important process that has contributed to the modern-day genomes of many eukaryotic species, including humans and our relatives. Given how recently biologists came to appreciate the importance of hybridization, there are basic unanswered questions about its genetic and evolutionary consequences. Addressing these questions from the single gene to the genomic scale is the major focus of research in my lab group. Hybridization is not simply a feature of a population's history; it can impact diverse biological processes from adaptation to disease. During the first four years of R35 funding in my lab group, we studied several fundamental genetic consequences of hybridization and developed new computational methods to study hybridization. Because the genomes of two species have been evolving is isolation, combining these genomes can have severe consequences. We used the swordtail model system developed by my lab to pinpoint the genetic interactions that breakdown in hybrids and the mechanisms through which they act. We will continue this work by building the first genome-wide map of such genetic interactions in vertebrates and by unravelling the molecular mechanisms that lead to melanoma and embryonic lethality in hybrids. My lab also studies broad scale principles governing where in the genome hybrid ancestry persists and where it is removed by selection. Our past work uncovered a key role of recombination rate and the density of conserved base pairs in shaping the dynamics of genetic exchange between species along the genome. We propose to continue this work to uncover additional processes shaping evolution after hybridization on a genome-wide scale, focusing on the role of structural rearrangements, divergence in transposable element families, and protein complexes. Together this research will help us understand the mechanisms shaping genome evolution after hybridization in species across the tree of life.