title: A potential role for glucose transporters in the evolution of human brain size.
abstract: Differences in cognitive abilities and the relatively large brain are among the most striking differences between humans and their closest primate relatives. The energy trade-off hypothesis predicts that a major shift in energy allocation among tissues occurred during human origins in order to support the remarkable expansion of a metabolically expensive brain. However, the molecular basis of this adaptive scenario is unknown. Two glucose transporters (SLC2A1 and SLC2A4) are promising candidates and present intriguing mutations in humans, resulting, respectively, in microcephaly and disruptions in whole-body glucose homeostasis. We compared SLC2A1 and SLC2A4 expression between humans, chimpanzees and macaques, and found compensatory and biologically significant expression changes on the human lineage within cerebral cortex and skeletal muscle, consistent with mediating an energy trade-off. We also show that these two genes are likely to have undergone adaptation and participated in the development and maintenance of a larger brain in the human lineage by modulating brain and skeletal muscle energy allocation. We found that these two genes show human-specific signatures of positive selection on known regulatory elements within their 5'-untranslated region, suggesting an adaptation of their regulation during human origins. This study represents the first case where adaptive, functional and genetic lines of evidence implicate specific genes in the evolution of human brain size.
authors: Biology Department, Duke University, Durham, NC, USA. ofedrigo@duke.edu
authors: Olivier
authors: O
authors: Fedrigo
authors: Adam D
authors: AD
authors: Pfefferle
authors: Courtney C
authors: CC
authors: Babbitt
authors: Ralph
authors: R
authors: Haygood
authors: Christine E
authors: CE
authors: Wall
authors: Gregory A
authors: GA
authors: Wray
mesh_terms: D000818:Animals; D001483:Base Sequence; D005075:Biological Evolution; D001921:Brain / Q000033:anatomy & histology* / Q000502:physiology*; D015870:Gene Expression; D051275:Glucose Transporter Type 4 / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D008251:Macaca; D008969:Molecular Sequence Data; D009929:Organ Size / Q000235:genetics; D002679:Pan troglodytes; D060888:Real-Time Polymerase Chain Reaction; D050611:Sodium-Phosphate Cotransporter Proteins, Type III / Q000096:biosynthesis* / Q000235:genetics; D013045:Species Specificity
chemical_list: D051275:Glucose Transporter Type 4; C493586:SLC20A1 protein, human; C495692:SLC2A4 protein, human; D050611:Sodium-Phosphate Cotransporter Proteins, Type III