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Mazen W. Karaman,1 Krishna Ramaswamy,1 Ann Moser,2 Paul A. Watkins,2 Oliver A. Ryder,3 and Joseph G. Hacia1 1Institute for Genetic Medicine, Abstract Although much is known about genetic variation in human and African great ape (chimpanzee, bonobo, and gorilla) genomes, less is known about variation in gene expression profiles within and among these species. This information is necessary for defining transcriptional regulatory networks that contribute to complex phenotypes unique to humans or the African great apes. We took a systematic approach to this problem by investigating gene expression profiles in well-defined cell populations from humans, bonobos, and gorillas. Overall, we found that gene expression profiles could predict the species but not the age of the fibroblast donor. Several differentially expressed genes observed in human and African great ape fibroblasts are involved in lipid metabolic pathways which are known to affect the central nervous and cardiovascular systems. To further explore this issue, we quantified the relative activities of lipid metabolic pathways in cultured fibroblasts from humans and African great apes and found they closely correlated with the gene expression patterns. We also observed a relationship between the dietary intake of specific lipids and their rates of metabolism in each species. Furthermore, we uncovered differential subcellular localization of proteins related to lipid metabolism in each species. This provides a novel explanation for the differential activities of specific metabolic pathways in human and non-human primates. Overall, these species-specific gene expression patterns and metabolic activities could have influenced the development of unique traits in humans and the African great apes. |