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Human brain evolution: insights from microarrays

Nature Reviews Genetics volume 5, pages 850–860 (2004)Cite this article

Key Points

  • Gene expression in the adult cerebral cortex has been compared in humans, chimpanzees and other primates in several independent microarray studies.

  • These studies yield qualitatively similar results when analysed in similar ways, despite differences in the cortical regions examined and the non-human species that were compared with humans.

  • A large number of genes, representing at least 2% of expressed sequences, are differentially expressed in the cortex of humans compared with chimpanzees, the animals that are most closely related to humans.

  • There is a bias towards genes showing increased, rather than decreased, expression levels in human cortex (that is, upregulation). This bias persists even when artefacts introduced by sequence differences between species are considered.

  • Tissues other than the brain do not show such a bias, but show similar numbers of genes with increased and decreased expression levels.

  • Gene-expression changes in the adult brain that occurred during human evolution were more pronounced than those that occurred during chimpanzee evolution.

  • There were in fact, fewer gene-expression changes between humans and chimpanzees in the brain than in non-neural tissue, such as that of the liver and heart.

  • Gene-ontology analyses indicate that the human brain was modified to support higher levels of neural activity.

Abstract

Several recent microarray studies have compared gene-expression patterns n humans, chimpanzees and other non-human primates to identify evolutionary changes that contribute to the distinctive cognitive and behavioural characteristics of humans. These studies support the surprising conclusion that the evolution of the human brain involved an upregulation of gene expression relative to non-human primates, a finding that could be relevant to understanding human cerebral physiology and function. These results show how genetic and genomic methods can shed light on the basis of human neural and cognitive specializations, and have important implications for neuroscience, anthropology and medicine.

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Figure 1: Phylogenetic relationships between humans and other primates.
Figure 2: Effect of interspecific sequence differences on oligonucleotide array hybridization.
Figure 3: Patterns of gene-expression changes between human and chimpanzee brains.
Figure 4: Agreement between different human–chimpanzee comparisons using oligonucleotide microarrays.

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Acknowledgements

T.M.P. and M.C. contributed equally to this work. We thank the different authors of the primate microarray studies for making their data sets publicly available, James Thomas for the comparison of the array probes to the chimpanzee genome sequence, and David Kornack for his insightful comments. We would also like to thank the James S. McDonnell Foundation for their support of our research through a Collaborative Activities Grant (T.P., D.H.G.) and acknowledge support from the National Institute of Mental Health (D.H.G.).

Author information

Authors and Affiliations

  1. Division of Neuroscience and Center for Behavioral Neuroscience, Yerkes National Primate Research Center, Emory University, 954 Gatewood Road, Atlanta, 30329, Georgia, USA

    Todd M. Preuss & Mario Cáceres

  2. Department of Pathology and Laboratory Medicine, Emory University School of Medicine, 1364 Clifton Road, Atlanta, 30322, Georgia, USA

    Todd M. Preuss

  3. Department of Human Genetics, Emory University School of Medicine, 615 Michael Street, Atlanta, 30322, Georgia, USA

    Mario Cáceres

  4. Department of Neurology and Center for Neurobehavioral Genetics, The Neuropsychiatric Institute, UCLA School of Medicine, 710 Westwood Plaza, Los Angeles, 90095, California, USA

    Michael C. Oldham & Daniel H. Geschwind

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  1. Todd M. Preuss
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  4. Daniel H. Geschwind
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Corresponding authors

Correspondence to Todd M. Preuss or Daniel H. Geschwind.

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DATABASES

OMIM

Alzheimer's disease

FURTHER INFORMATION

Affymetrix GeneChip Files

Affymetrix GeneChip Microarray Data Files

Affymetrix GeneChips in TeraGenomics

Chimpanzee Genome Project

Functional Genomics and Bioinformatics

Human Genome Project

Joseph Hacia's Laboratory — Karaman Supplemental Data

Glossary

HUMAN SPECIALIZATION

A phenotypic characteristic of modern humans that has emerged since the divergence of the human lineage from the common ancestor of humans and chimpanzees.

POSITIVE SELECTION

A form of evolutionary change in which a mutation has a favourable effect and increases its frequency in the population at a rate greater than that predicted by neutral drift.

AGONAL STATE

The state of an individual during the time immediately preceeding death. For example, prolonged hypoxia or acidosis, can significantly affect gene expression.

OUTGROUP METHOD

Comparison of closely related species to infer the state of a common ancestor.

OLIGONUCLEOTIDE ARRAY

A microarray made with synthetic probes, usually 25–60 bases long, each designed to hybridize to a specific mRNA. These are fabricated either in situ or by deposition and attachment onto a solid surface. The oligonucleotide arrays that are currently available can measure expression levels for 10,000–40,000 genes simultaneously.

INDELS

Insertions or deletions of DNA sequences in chromosomes.

NORTHERN BLOT

An experimental technique for determining the abundance and size of the transcript(s) for a particular gene in a given tissue. mRNAs are separated electrophoretically on a gel and then transferred to a membrane (blot) by capillary action. The membrane is then immersed in a labelled probe designed to hybridize to a specific mRNA.

RT-PCR

Reverse transcription PCR. Using the enzyme reverse transcriptase, RNA is converted into DNA, which is then amplified with specific primers.

NORMALIZATION

Mathematical processing of raw data to reduce the effects of variables introduced by the experimental design or method used. For microarrays, such variables might include differences in fluorescent dye incorporation, the amount of cRNA or cDNA hybridized to the array, hybridization conditions or the arrays themselves.

cDNA MICROARRAY

A microarray made by deposition of gene-specific, PCR-amplified inserts from cDNA clones, which can be from several hundred to several thousand bases long. cDNA arrays typically measure expression levels for 5,000–30,000 genes.

QUANTITATIVE REAL-TIME RT-PCR

A procedure in which DNA amplification in a PCR reaction is measured during its log-linear phase by monitoring the accumulating signal that is provided by a fluorescent dye or gene-specific fluorescent probe incorporated into the PCR product.

DISTANCE METRIC

A measure of similarity or dissimilarity that can be used to organize groups according to their degree of relation to one another. For example, the Euclidian distance metric that distinguishes two genes, or groups of genes, is often defined as the square root of the sum of their squared expression differences.

GENE ONTOLOGY

A framework for classifying gene products hierarchically in three dimensions according to the biological process in which they are involved, the molecular function that they perform and the cellular component in which they are located.

NETWORK ANALYSIS

Analysis of the individual interactions between constituents, which, when grouped together, describe a network. In the case of gene-expression data, network analysis entails the identification of relationships among genes or groups of genes across different experimental conditions or tissue samples.

DIVERSIFYING SELECTION

Natural selection against the mean value of a quantitative trait, therefore favouring individuals at the two tails of the phenotypic distribution.

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Preuss, T., Cáceres, M., Oldham, M. et al. Human brain evolution: insights from microarrays. Nat Rev Genet 5, 850–860 (2004). https://doi.org/10.1038/nrg1469

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