title: Comparative metabolomics in primates reveals the effects of diet and gene regulatory variation on metabolic divergence.
abstract: Human diets differ from those of non-human primates. Among few obvious differences, humans consume more meat than most non-human primates and regularly cook their food. It is hypothesized that a dietary shift during human evolution has been accompanied by molecular adaptations in metabolic pathways. Consistent with this notion, comparative studies of gene expression levels in primates have found that the regulation of genes with metabolic functions tend to evolve rapidly in the human lineage. The metabolic consequences of these regulatory differences, however, remained unknown. To address this gap, we performed a comparative study using a combination of gene expression and metabolomic profiling in livers from humans, chimpanzees, and rhesus macaques. We show that dietary differences between species have a strong effect on metabolic concentrations. In addition, we found that differences in metabolic concentration across species are correlated with inter-species differences in the expression of the corresponding enzymes, which control the same metabolic reaction. We identified a number of metabolic compounds with lineage-specific profiles, including examples of human-species metabolic differences that may be directly related to dietary differences.
authors: 1] Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN, 55455 [2] Department of Ecology, Evolution, and Behavior, University of Minnesota, St. Paul, MN, 55108.
authors: Ran
authors: R
authors: Blekhman
authors: Department of Biology, Penn State University, University Park, PA, 16802.
authors: George H
authors: GH
authors: Perry
authors: UC Davis Genome Center, University of California, Davis, CA, 95616.
authors: Sevini
authors: S
authors: Shahbaz
authors: UC Davis Genome Center, University of California, Davis, CA, 95616.
authors: Oliver
authors: O
authors: Fiehn
authors: Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, 14853.
authors: Andrew G
authors: AG
authors: Clark
authors: Department of Human Genetics, University of Chicago, Chicago, IL, 61637.
authors: Yoav
authors: Y
authors: Gilad
mesh_terms: D000818:Animals; D005075:Biological Evolution; D003296:Cooking; D004032:Diet; D015870:Gene Expression; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008253:Macaca mulatta / Q000235:genetics / Q000378:metabolism*; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D055432:Metabolomics / Q000706:statistics & numerical data*; D002679:Pan troglodytes / Q000235:genetics / Q000378:metabolism*; D013045:Species Specificity