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

doi:10.1073/pnas.2135499100

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

^*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 Biosciences, 9875 Towne Centre Drive, San Diego, CA 92121

Communicated by Jon H. Kaas, Vanderbilt University, Nashville, TN, August 27, 2003 (received for review June 6, 2003)

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 ≈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.

Footnotes

↵ ∥ To whom correspondence should be addressed. E-mail: carrolee_barlow{at}merck.com.
Abbreviations: Hs, Homo sapiens; Pt, Pan troglodytes; Mm, Macaca mulatta; CA2, carbonic anhydrase II.
Data deposition. The sequences reported in this paper have been deposited in the GenBank database (accession nos. AY369785–AY369856).
↵ ** For additional references to gene functions, see the LocusLink (www.ncbi.nlm.nih.gov/LocusLink), OMIM (www.ncbi.nlm.nih.gov/Omim), and SOURCE (http://source.stanford.edu/cgi-bin/sourceSearch) databases.