Rapid metabolic evolution in human prefrontal cortex

Fu, Xing
Giavalisco, Patrick
Liu, Xiling
Catchpole, Gareth
Fu, Ning
Ning, Zhi-Bin
Guo, Song
Yan, Zheng
Somel, Mehmet
Paeaebo, Svante
Zeng, Rong
Willmitzer, Lothar
Khaitovich, Philipp
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.


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Over the course of ontogenesis, the human brain and human cognitive abilities develop in parallel, resulting in a phenotype strikingly distinct from that of other primates. Here, we used microarrays and RNA-sequencing to examine human-specific gene expression changes taking place during postnatal brain development in the prefrontal cortex and cerebellum of humans, chimpanzees, and rhesus macaques. We show that the most prominent human-specific expression change affects genes associated with synaptic functio...
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The perception and description of space are one of the most fundamental phenomena in human cognition and evolution. Knowing where we are and telling allies about it is vital information from an evolutionary perspective. There is more than one way to define spatial scenes, and we choose one of these ways without even realizing it. Literature examines the spatial linguistic systems to find out what drives and provoke these differences. Linguistic elements that define space generally examined as topological de...
Transcriptomic insights into human brain evolution: acceleration, neutrality, heterochrony
Somel, Mehmet; Liu, Xiling (Elsevier BV, 2014-12-01)
Primate brain transcriptome comparisons within the last 12 years have yielded interesting but contradictory observations on how the transcriptome evolves, and its adaptive role in human cognitive evolution. Since the human-chimpanzee common ancestor, the human prefrontal cortex transcriptome seems to have evolved more than that of the chimpanzee. But at the same time, most expression differences among species, especially those observed in adults, appear as consequences of neutral evolution at cis-regulatory...
MicroRNA-Driven Developmental Remodeling in the Brain Distinguishes Humans from Other Primates
Somel, Mehmet; Tang, Lin; Yan, Zheng; Hu, Haiyang; Guo, Song; Jiang, Xi; Zhang, Xiaoyu; Xu, Guohua; Xie, Gangcai; Li, Na; Hu, Yuhui; Chen, Wei; Paeaebo, Svante; Khaitovich, Philipp (2011-12-01)
While multiple studies have reported the accelerated evolution of brain gene expression in the human lineage, the mechanisms underlying such changes are unknown. Here, we address this issue from a developmental perspective, by analyzing mRNA and microRNA (miRNA) expression in two brain regions within macaques, chimpanzees, and humans throughout their lifespan. We find that constitutive gene expression divergence (species differences independent of age) is comparable between humans and chimpanzees. However, ...
Evolution of Primate Gene Expression: Drift and Corrective Sweeps?
Chaix, R.; Somel, Mehmet; Kreil, D. P.; Khaitovich, P.; Lunter, G. A. (Genetics Society of America, 2008-11-01)
Changes in gene expression play an important: role in species' evolution. Earlier studies uncovered evidence that the effect of mutations on expression levels within the primate order is skewed, with many small downregulations balanced by fewer but larger upregulations. In addition, brain-expressed genes appeared to show an increased rate of evolution on the branch leading to human. However, the lack of a mathematical model adequately describing the evolution of gene expression precluded the rigorous establ...
Citation Formats
X. Fu et al., “Rapid metabolic evolution in human prefrontal cortex,” PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, pp. 6181–6186, 2011, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/46490.