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Cited by 491Primate Behavior and EcologyGenetics and Neurodevelopmental DisordersGenomic variations and chromosomal abnormalities

Elevated gene expression levels distinguish human from non-human primate brains

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Cáceres, Mario, Lachuer, Joel, Zapala, Matthew A., Redmond, John C., Kudo, Lili, Geschwind, Daniel H., Lockhart, David J., Preuss, Todd M. +1 more·2003·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.2135499100PMC PMC240739
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Abstract

Little is known about how the human brain differs from that of our closest relatives. To investigate the genetic basis of human specializations in brain organization and cognition, we compared gene expression profiles for the cerebral cortex of humans, chimpanzees, and rhesus macaques by using several independent techniques. We identified 169 genes that exhibited expression differences between human and chimpanzee cortex, and 91 were ascribed to the human lineage by using macaques as an outgroup. Surprisingly, most differences between the brains of humans and non-human primates involved up-regulation, with approximately 90% of the genes being more highly expressed in humans. By contrast, in the comparison of human and chimpanzee heart and liver, the numbers of up- and down-regulated genes were nearly identical. Our results indicate that the human brain displays a distinctive pattern of gene expression relative to non-human primates, with higher expression levels for many genes belonging to a wide variety of functional classes. The increased expression of these genes could provide the basis for extensive modifications of cerebral physiology and function in humans and suggests that the human brain is characterized by elevated levels of neuronal activity.

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  • This finding is consistent with previous microarray gene expression profiling studies, extending the conclusion further by providing cellular level details.

    “This finding is consistent with previous microarray gene expression profiling studies (Caceres et al., 2003; Gu and Gu, 2003; Johnson et al., 2009; Miller et al., 2010; Oldham et al., 2008), extending the conclusion further by providing cellular level details.”

    From Large-Scale Cellular-Resolution Gene Profiling in Human Neocortex Reveals Species-Specific Molecular Signatures (2012) · cites this paper as Caceres et al., 2003

  • This scenario reconciles human brain metabolism with comparative genetic analyses showing that genes related to cell metabolism are among those with larger changes in human evolution and evidence of evolutionary pressure for high rates of aerobic energy consumption.

    “This scenario reconciles human brain metabolism with comparative genetic analyses that show that genes related to cell metabolism are among those that exhibit the larger changes in human evolution [9], [10], with evidence of evolutionary pressure for high rates of aerobic energy consumption [52].”

    From Scaling of Brain Metabolism with a Fixed Energy Budget per Neuron: Implications for Neuronal Activity, Plasticity and Evolution (2011) · cites this paper as [9]

  • Genes involved in neuronal signaling and energy production are up-regulated in the human neocortex compared with chimpanzees and other great apes.

    “recent microarray studies have shown that genes involved in neuronal signaling and energy production are up-regulated in the human neocortex compared with chimpanzees and other great apes (4, 5).”

    From Evolution of increased glia–neuron ratios in the human frontal cortex (2006) · cites this paper as [5]

  • The gene encoding carbonic anhydrase 2, CA2, is up-regulated in the human cortex compared with chimpanzees and other primates.

    “For example, the gene encoding carbonic anhydrase 2, CA2, is up-regulated in the human cortex compared with chimpanzees and other primates (5).”

    From Evolution of increased glia–neuron ratios in the human frontal cortex (2006) · cites this paper as [5]

  • Comparative microarray experiments have revealed up-regulation of genes in the human neocortex related to energy metabolism.

    “Comparative microarray experiments have also revealed up-regulation of genes in the human neocortex related to energy metabolism (4, 5).”

    From Evolution of increased glia–neuron ratios in the human frontal cortex (2006) · cites this paper as [5]

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Authors
Cáceres, M., Lachuer, J., Zapala, M. A., Redmond, J. C., Kudo, L., Geschwind, D. H., Lockhart, D. J., Preuss, T. M., & Barlow, C.
Affiliations
  • Salk Institute for Biological Studies (US)
  • Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037; Division of Neuroscience and Center for Behavioral Neuroscience, Yerkes Primate Center, and Department of Pathology and Laboratory Medicine, Emory University, 954 Gatewood Road, Atlanta, GA 30329; Program in Neurogenetics, Department of Neurology, Reed Neurological Research Center, University of California School of Medicine, 710 Westwood Plaza, Los Angeles, CA 90095; and Ambit...
Corresponding author
Barlow, Carrolee
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2003-10-13
Volume
100
Issue
22
Pages
13030-13035
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.2135499100
PMC
PMC240739
OpenAlex
W2029747645
Cited by
491
References
45
Citations by year
2026: 8 · 2025: 8 · 2024: 11 · 2023: 16 · 2022: 9 · 2021: 12 · 2020: 21 · 2019: 16 · 2018: 13 · 2017: 13 · 2016: 18 · 2015: 14 · 2014: 11 · 2013: 27 · 2012: 33
FWCI
52.44
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • James S. McDonnell Foundation
  • National Institute of Mental Health
Topics
  • Social Sciences › Psychology › Social Psychology › Primate Behavior and Ecology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
Keywords
human brain evolution, human-chimpanzee comparison, rhesus monkeys, upregulated genes, human-specific genes, neuronal activity, brain organization, comparative genomics
MeSH terms
Animals, Brain, Cerebral Cortex, Pan troglodytes, Humans, Macaca mulatta, Molecular Sequence Data, Primates, Species Specificity, Hominidae, Gene Expression, In Situ Hybridization, DNA, Complementary, Reverse Transcriptase Polymerase Chain Reaction, Oligonucleotide Array Sequence Analysis

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