title: Comparative expression analysis of the phosphocreatine circuit in extant primates: Implications for human brain evolution.
abstract: While the hominid fossil record clearly shows that brain size has rapidly expanded over the last ~2.5 M.yr. the forces driving this change remain unclear. One popular hypothesis proposes that metabolic adaptations in response to dietary shifts supported greater encephalization in humans. An increase in meat consumption distinguishes the human diet from that of other great apes. Creatine, an essential metabolite for energy homeostasis in muscle and brain tissue, is abundant in meat and was likely ingested in higher quantities during human origins. Five phosphocreatine circuit proteins help regulate creatine utilization within energy demanding cells. We compared the expression of all five phosphocreatine circuit genes in cerebral cortex, cerebellum, and skeletal muscle tissue for humans, chimpanzees, and rhesus macaques. Strikingly, SLC6A8 and CKB transcript levels are higher in the human brain, which should increase energy availability and turnover compared to non-human primates. Combined with other well-documented differences between humans and non-human primates, this allocation of energy to the cerebral cortex and cerebellum may be important in supporting the increased metabolic demands of the human brain.
authors.affiliation: Biology Department, Duke University, Durham, USA.|Institute for Genome Sciences & Policy, Duke University, Durham, USA.
authors.forename: Adam D
authors.initials: AD
authors.lastname: Pfefferle
authors.affiliation: Biology Department, Duke University, Durham, USA.|Institute for Genome Sciences & Policy, Duke University, Durham, USA.
authors.forename: Lisa R
authors.initials: LR
authors.lastname: Warner
authors.affiliation: Biology Department, Duke University, Durham, USA.
authors.forename: Catrina W
authors.initials: CW
authors.lastname: Wang
authors.affiliation: Biology Department, Duke University, Durham, USA.|Institute for Genome Sciences & Policy, Duke University, Durham, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Nielsen
authors.affiliation: Biology Department, Duke University, Durham, USA.|Institute for Genome Sciences & Policy, Duke University, Durham, USA.
authors.forename: Courtney C
authors.initials: CC
authors.lastname: Babbitt
authors.affiliation: Biology Department, Duke University, Durham, USA.|Institute for Genome Sciences & Policy, Duke University, Durham, USA.
authors.forename: Olivier
authors.initials: O
authors.lastname: Fedrigo
authors.affiliation: Biology Department, Duke University, Durham, USA.|Institute for Genome Sciences & Policy, Duke University, Durham, USA.|Department of Evolutionary Anthropology, Duke University, Durham, USA.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Wray
mesh_terms: D000818:Animals; D005075:Biological Evolution; D001921:Brain / Q000378:metabolism*; D052276:Creatine Kinase, BB Form / Q000235:genetics; D052283:Creatine Kinase, MM Form / Q000235:genetics; D052281:Creatine Kinase, Mitochondrial Form / Q000235:genetics; D006801:Humans; D008253:Macaca mulatta; D026901:Membrane Transport Proteins / Q000235:genetics; D018482:Muscle, Skeletal / Q000378:metabolism; D002679:Pan troglodytes; D010725:Phosphocreatine / Q000378:metabolism*; D011323:Primates / Q000235:genetics*
chemical_list: D026901:Membrane Transport Proteins; C080679:creatine transporter; D010725:Phosphocreatine; D052276:Creatine Kinase, BB Form; D052283:Creatine Kinase, MM Form; D052281:Creatine Kinase, Mitochondrial Form