Evolution can alter physiology through protein mutations, producing mechanistic parallels between human disease and animal adaptations. In the genomics era, the advanced physiological innovations produced by natural selection can begin to serve as an untapped source of therapeutic innovation. Our lab applies this understanding towards reverse engineering: (1) the advanced visual systems of dim-light specialists (owls, bats, whales); (2) the extreme energy production capabilities of birds and horses. In our first research theme, we discovered that rhodopsin, the dim-light visual pigment, also has a counterintuitive role in protecting the retina against bright-light damage.  Mutations in rhodopsin and its binding partner, arrestin, have evolved to protect these species against the same toxic photoproducts associated with age-related macular degeneration in humans. In our second research theme, we discovered that the extreme energy demands of birds and horses are met by protein mutations that hyperactivate oxygen metabolism while maintaining redox homeostasis. Although this phenotype is normally associated with human cancers, our research indicates that these lineages avoid this deleterious side-effect through second-order compensatory mutations at other loci. In birds, these mutations also appear to serve moonlighting roles in extending lifespan and regulating feather development.