title: Rapid metabolic evolution in human prefrontal cortex.
abstract: Human evolution is characterized by the rapid expansion of brain size and drastic increase in cognitive capabilities. It has long been suggested that these changes were accompanied by modifications of brain metabolism. Indeed, human-specific changes on gene expression or amino acid sequence were reported for a number of metabolic genes, but actual metabolite measurements in humans and apes have remained scarce. Here, we investigate concentrations of more than 100 metabolites in the prefrontal and cerebellar cortex in 49 humans, 11 chimpanzees, and 45 rhesus macaques of different ages using gas chromatography-mass spectrometry (GC-MS). We show that the brain metabolome undergoes substantial changes, both ontogenetically and evolutionarily: 88% of detected metabolites show significant concentration changes with age, whereas 77% of these metabolic changes differ significantly among species. Although overall metabolic divergence reflects phylogenetic relationships among species, we found a fourfold acceleration of metabolic changes in prefrontal cortex compared with cerebellum in the human lineage. These human-specific metabolic changes are paralleled by changes in expression patterns of the corresponding enzymes, and affect pathways involved in synaptic transmission, memory, and learning.
authors: Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Chinese Academy of Sciences, 200031 Shanghai, China.
authors: Xing
authors: X
authors: Fu
authors: Patrick
authors: P
authors: Giavalisco
authors: Xiling
authors: X
authors: Liu
authors: Gareth
authors: G
authors: Catchpole
authors: Ning
authors: N
authors: Fu
authors: Zhi-Bin
authors: ZB
authors: Ning
authors: Song
authors: S
authors: Guo
authors: Zheng
authors: Z
authors: Yan
authors: Mehmet
authors: M
authors: Somel
authors: Svante
authors: S
authors: Pääbo
authors: Rong
authors: R
authors: Zeng
authors: Lothar
authors: L
authors: Willmitzer
authors: Philipp
authors: P
authors: Khaitovich
mesh_terms: D005075:Biological Evolution; D006801:Humans; D055442:Metabolome; D017397:Prefrontal Cortex / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*
chemical_list: D011506:Proteins