Pseudogenization of UDP-glucuronosyltransferase (UGT) 1A6 in Felidae: Potential Role of Diet and Evidence for Similar Events in Other Carnivore Species

Environmental exposure to toxic compounds is proposed to have a major role in the evolution of the drug metabolizing enzymes in animals. In this study, we explored the relationship between the level of exposure to plant-derived phenolic toxins from the diet within the order Carnivora and the accumulation of multiple inactivating genetic mutations (pseudogenization) in the major phenol detoxification enzyme, UDP-glucuronosyltransferase (UGT) 1A6. We found evidence for pseudogenization of the UGT1A6 gene in all 19 Felidae species studied. Furthermore out of 44 other species evaluated, both brown hyena and Northern elephant seal showed inactivating UGT1A6 mutations. An exhaustive literature review identified 29 out of 46 species evaluated as hypercarnivores (or true carnivores), which should have minimal exposure to dietary phytotoxins. Importantly, all species with UGT1A6 defects were hypercarnivores, supporting a critical role for diet in the pseudogenization of UGT1A6, and suggesting these species may also be susceptible to pollutant bioaccumulation.