PIs are Jeff Yoder, Alex Dornburg, and Michael Fisk, NCSU. Unraveling the evolutionary history of certain fish genes continues to inform important aspects of human health. We share 70 percent of our genes with fish, and advances in genetic engineering allow us to test how these genes contribute to everything from behavior to disease. While several fish species are already used as model systems, all contain a duplicated genome. This genome duplication is a major problem that makes relating genetic mechanisms between humans and fish especially difficult. Consequently, this raises the challenge of identifying species that bridge the genetic gap between model fish and humans. Fortunately, several species of living freshwater fishes may well be the missing link – gar, bowfin and bichirs. Referred to by Darwin as living fossils, these ancient fish lineages do not possess a duplicated genome. Instead they contain a mix of genes that sometimes more closely resemble those in humans rather than fish. This amazing similarity can be utilized when we develop a better understanding of how the genomes of these living fossils evolved, which will be critical in linking the genes of fish to humans. Our work will investigate genes relevant to human immune function also shared by gar, bowfin and bichir species. We will improve our understanding of how immune genes evolved by comparing genes within and between these ancient groups, as well as with other model fish species and humans. Our work will provide an important framework for effectively translating genetic research in model fish to human health and disease.