Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 12 April 2002:
Vol. 296. no. 5566, pp. 340 - 343
DOI: 10.1126/science.1068996
Prev | Table of Contents | Next

Reports

Intra- and Interspecific Variation in Primate Gene Expression Patterns

Wolfgang Enard,1* Philipp Khaitovich,1* Joachim Klose,2 Sebastian Zöllner,1 Florian Heissig,1 Patrick Giavalisco,3 Kay Nieselt-Struwe,4 Elaine Muchmore,56 Ajit Varki,5 Rivka Ravid,7 Gaby M. Doxiadis,8 Ronald E. Bontrop,8 Svante Pääbo1dagger

Although humans and their closest evolutionary relatives, the chimpanzees, are 98.7% identical in their genomic DNA sequences, they differ in many morphological, behavioral, and cognitive aspects. The underlying genetic basis of many of these differences may be altered gene expression. We have compared the transcriptome in blood leukocytes, liver, and brain of humans, chimpanzees, orangutans, and macaques using microarrays, as well as protein expression patterns of humans and chimpanzees using two-dimensional gel electrophoresis. We also studied three mouse species that are approximately as related to each other as are humans, chimpanzees, and orangutans. We identified species-specific gene expression patterns indicating that changes in protein and gene expression have been particularly pronounced in the human brain.

1 Max-Planck-Institute for Evolutionary Anthropology, Inselstrasse 22, D-04103 Leipzig, Germany.
2 Institut fuer Humangenetik Charité, D-13353 Berlin, Germany.
3 Max-Planck-Institute for Molecular Genetics, D-14195 Berlin, Germany.
4 Max-Planck-Institute of Biophysical Chemistry, D-37077 Göttingen, Germany.
5 University of California San Diego, La Jolla, CA 92093, USA.
6 VA Medical Center, San Diego, La Jolla, CA 92093, USA.
7 The Netherlands Brain Bank, Amsterdam, the Netherlands.
8 Biomedical Primate Research Centre, Rijswijk, the Netherlands.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: paabo{at}eva.mpg.de

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
The complex of TFII-I, PARP1, and SFPQ proteins regulates the DYX1C1 gene implicated in neuronal migration and dyslexia.
I. Tapia-Paez, K. Tammimies, S. Massinen, A. L. Roy, and J. Kere (2008)
FASEB J 22, 3001-3009
   Abstract »    Full Text »    PDF »
Natural Variation in Gene Expression Between Wild and Weedy Populations of Helianthus annuus.
Z. Lai, N. C. Kane, Y. Zou, and L. H. Rieseberg (2008)
Genetics 179, 1881-1890
   Abstract »    Full Text »    PDF »
Long-term In vitro Expansion Alters the Biology of Adult Mesenchymal Stem Cells.
R. Izadpanah, D. Kaushal, C. Kriedt, F. Tsien, B. Patel, J. Dufour, and B. A. Bunnell (2008)
Cancer Res. 68, 4229-4238
   Abstract »    Full Text »    PDF »
Cross-study validation and combined analysis of gene expression microarray data.
E. Garrett-Mayer, G. Parmigiani, X. Zhong, L. Cope, and E. Gabrielson (2008)
Biostat. 9, 333-354
   Abstract »    Full Text »    PDF »
Sequence Variation of MicroRNAs and Their Binding Sites in Arabidopsis.
I. M. Ehrenreich and M. D. Purugganan (2008)
Plant Physiology 146, 1974-1982
   Abstract »    Full Text »    PDF »
Neutrality, Compensation, and Negative Selection during Evolution of B-Cell Development Transcriptomes.
R. Hoffmann, C. Lottaz, T. Kuhne, A. Rolink, and F. Melchers (2007)
Mol. Biol. Evol. 24, 2610-2618
   Abstract »    Full Text »    PDF »
Increased Cortical Expression of Two Synaptogenic Thrombospondins in Human Brain Evolution.
M. Caceres, C. Suwyn, M. Maddox, J. W. Thomas, and T. M. Preuss (2007)
Cereb Cortex 17, 2312-2321
   Abstract »    Full Text »    PDF »
Senescence-associated genes induced during compatible viral interactions with grapevine and Arabidopsis.
C Espinoza, C Medina, S Somerville, and P Arce-Johnson (2007)
J. Exp. Bot.
   Abstract »    Full Text »    PDF »
Detecting genetic variation in microarray expression data.
J. A. Greenhall, M. A. Zapala, M. Caceres, O. Libiger, C. Barlow, N. J. Schork, and D. J. Lockhart (2007)
Genome Res. 17, 1228-1235
   Abstract »    Full Text »    PDF »
Inference of Expression-Dependent Negative Selection Based on Polymorphism and Divergence in the Human Genome.
N. Osada (2007)
Mol. Biol. Evol. 24, 1622-1626
   Abstract »    Full Text »    PDF »
Human and Simian Immunodeficiency Virus-Mediated Upregulation of the Apoptotic Factor TRAIL Occurs in Antigen-Presenting Cells from AIDS-Susceptible but Not from AIDS-Resistant Species.
N. Kim, A. Dabrowska, R. G. Jenner, and A. Aldovini (2007)
J. Virol. 81, 7584-7597
   Abstract »    Full Text »    PDF »
Class prediction of closely related plant varieties using gene expression profiling.
G Ancillo, J Gadea, J Forment, J Guerri, and L Navarro (2007)
J. Exp. Bot. 58, 1927-1933
   Abstract »    Full Text »    PDF »
Using DNA microarrays to study gene expression in closely related species.
A. Oshlack, A. E. Chabot, G. K. Smyth, and Y. Gilad (2007)
Bioinformatics 23, 1235-1242
   Abstract »    Full Text »    PDF »
Comparative environmental genomics in non-model species: using heterologous hybridization to DNA-based microarrays.
B. A. Buckley (2007)
J. Exp. Biol. 210, 1602-1606
   Abstract »    Full Text »    PDF »
The biological importance of measuring individual variation.
D. L. Crawford and M. F. Oleksiak (2007)
J. Exp. Biol. 210, 1613-1621
   Abstract »    Full Text »    PDF »
Chimpanzee, Orangutan, Mouse, and Human Cell Cycle Promoters Exempt CCAAT Boxes and CHR Elements from Interspecies Differences.
G. A. Muller, F. Heissig, and K. Engeland (2007)
Mol. Biol. Evol. 24, 814-826
   Abstract »    Full Text »    PDF »
Tissue-driven hypothesis of genomic evolution and sequence-expression correlations.
X. Gu and Z. Su (2007)
PNAS 104, 2779-2784
   Abstract »    Full Text »    PDF »
Impact of Transcriptional Properties on Essentiality and Evolutionary Rate.
J. K. Choi, S. C. Kim, J. Seo, S. Kim, and J. Bhak (2007)
Genetics 175, 199-206
   Abstract »    Full Text »    PDF »
Conservation and evolution of gene coexpression networks in human and chimpanzee brains.
M. C. Oldham, S. Horvath, and D. H. Geschwind (2006)
PNAS 103, 17973-17978
   Abstract »    Full Text »    PDF »
Serum Peptidome Patterns That Distinguish Metastatic Thyroid Carcinoma from Cancer-free Controls Are Unbiased by Gender and Age.
J. Villanueva, A. J. Martorella, K. Lawlor, J. Philip, M. Fleisher, R. J. Robbins, and P. Tempst (2006)
Mol. Cell. Proteomics 5, 1840-1852
   Abstract »    Full Text »    PDF »
Inheritance Patterns of Transcript Levels in F1 Hybrid Mice.
X. Cui, J. Affourtit, K. R. Shockley, Y. Woo, and G. A. Churchill (2006)
Genetics 174, 627-637
   Abstract »    Full Text »    PDF »
Profile of Svante Paabo.
N. Zagorski (2006)
PNAS 103, 13575-13577
   Full Text »    PDF »
Identification of the REST regulon reveals extensive transposable element-mediated binding site duplication.
R. Johnson, R. J. Gamblin, L. Ooi, A. W. Bruce, I. J. Donaldson, D. R. Westhead, I. C. Wood, R. M. Jackson, and N. J. Buckley (2006)
Nucleic Acids Res. 34, 3862-3877
   Abstract »    Full Text »    PDF »
Origination and evolution of a human-specific transmembrane protein gene, c1orf37-dup.
H. Yu, H. Jiang, Q. Zhou, J. Yang, Y. Cun, B. Su, C. Xiao, and W. Wang (2006)
Hum. Mol. Genet. 15, 1870-1875
   Abstract »    Full Text »    PDF »
The evolution of embryonic gene expression in sea urchins.
G. A. Wray (2006)
Integr. Comp. Biol. 46, 233-242
   Abstract »    Full Text »    PDF »
Low Rates of Expression Profile Divergence in Highly Expressed Genes and Tissue-Specific Genes During Mammalian Evolution.
B.-Y. Liao and J. Zhang (2006)
Mol. Biol. Evol. 23, 1119-1128
   Abstract »    Full Text »    PDF »
Expression Profiles of Endogenous Retroviruses in Old World Monkeys.
A. Stengel, C. Roos, G. Hunsmann, W. Seifarth, C. Leib-Mosch, and A. D. Greenwood (2006)
J. Virol. 80, 4415-4421
   Abstract »    Full Text »    PDF »
Evolutionary expansion and divergence in the ZNF91 subfamily of primate-specific zinc finger genes.
A. T. Hamilton, S. Huntley, M. Tran-Gyamfi, D. M. Baggott, L. Gordon, and L. Stubbs (2006)
Genome Res. 16, 584-594
   Abstract »    Full Text »    PDF »
Mapping cis-acting regulatory variation in recombinant congenic strains.
P. D. Lee, B. Ge, C. M. T. Greenwood, D. Sinnett, Y. Fortin, S. Brunet, A. Fortin, M. Takane, E. Skamene, T. Pastinen, et al. (2006)
Physiol Genomics 25, 294-302
   Abstract »    Full Text »    PDF »
Neutral and adaptive variation in gene expression.
A. Whitehead and D. L. Crawford (2006)
PNAS 103, 5425-5430
   Abstract »    Full Text »    PDF »
Evolutionary Conservation of Expression Profiles Between Human and Mouse Orthologous Genes.
B.-Y. Liao and J. Zhang (2006)
Mol. Biol. Evol. 23, 530-540
   Abstract »    Full Text »    PDF »
Abundant novel transcriptional units and unconventional gene pairs on human chromosome 22.
L. Lipovich and M.-C. King (2006)
Genome Res. 16, 45-54
   Abstract »    Full Text »    PDF »
Comparing the human and chimpanzee genomes: Searching for needles in a haystack.
A. Varki and T. K. Altheide (2005)
Genome Res. 15, 1746-1758
   Abstract »    Full Text »    PDF »
Genetic Analysis of Variation in Gene Expression in Arabidopsis thaliana.
M. Vuylsteke, F. van Eeuwijk, P. Van Hummelen, M. Kuiper, and M. Zabeau (2005)
Genetics 171, 1267-1275
   Abstract »    Full Text »    PDF »
Sub-array normalization subject to differentiation.
C. Cheng and L. M. Li (2005)
Nucleic Acids Res. 33, 5565-5573
   Abstract »    Full Text »    PDF »
A genome-wide survey of structural variation between human and chimpanzee.
T. L. Newman, E. Tuzun, V. A. Morrison, K. E. Hayden, M. Ventura, S. D. McGrath, M. Rocchi, and E. E. Eichler (2005)
Genome Res. 15, 1344-1356
   Abstract »    Full Text »    PDF »
Substitution Rate and Structural Divergence of 5'UTR Evolution: Comparative Analysis Between Human and Cynomolgus Monkey cDNAs.
N. Osada, M. Hirata, R. Tanuma, J. Kusuda, M. Hida, Y. Suzuki, S. Sugano, T. Gojobori, C.-K. J. Shen, C.-I Wu, et al. (2005)
Mol. Biol. Evol. 22, 1976-1982
   Abstract »    Full Text »    PDF »
Parallel Patterns of Evolution in the Genomes and Transcriptomes of Humans and Chimpanzees.
P. Khaitovich, I. Hellmann, W. Enard, K. Nowick, M. Leinweber, H. Franz, G. Weiss, M. Lachmann, and S. Paabo (2005)
Science 309, 1850-1854
   Abstract »    Full Text »    PDF »
Independent intrachromosomal recombination events underlie the pericentric inversions of chimpanzee and gorilla chromosomes homologous to human chromosome 16.
V. Goidts, J. M. Szamalek, P. J. de Jong, D. N. Cooper, N. Chuzhanova, H. Hameister, and H. Kehrer-Sawatzki (2005)
Genome Res. 15, 1232-1242
   Abstract »    Full Text »    PDF »
Comparison of Non-Human Primate and Human Whole Blood Tissue Gene Expression Profiles.
J. F. Dillman III and C. S. Phillips (2005)
Toxicol. Sci. 87, 306-314
   Abstract »    Full Text »    PDF »
Global gene expression as a function of germline genetic variation.
D. French, M. R. Wilkinson, W. Yang, L. de Chaisemartin, E. H. Cook, S. Das, M. J. Ratain, W. E. Evans, J. R. Downing, C.-H. Pui, et al. (2005)
Hum. Mol. Genet. 14, 1621-1629
   Abstract »    Full Text »    PDF »
Toward a Neutral Evolutionary Model of Gene Expression.
P. Khaitovich, S. Paabo, and G. Weiss (2005)
Genetics 170, 929-939
   Abstract »    Full Text »    PDF »
The response to anti-TNF-{alpha} treatment: gene regulation at the bedside.
N. de Vries and P. P. Tak (2005)
Rheumatology 44, 705-707
   Full Text »    PDF »
Multi-species microarrays reveal the effect of sequence divergence on gene expression profiles.
Y. Gilad, S. A. Rifkin, P. Bertone, M. Gerstein, and K. P. White (2005)
Genome Res. 15, 674-680
   Abstract »    Full Text »    PDF »
Genetic Architecture of Transcript-Level Variation in Differentiating Xylem of a Eucalyptus Hybrid.
M. Kirst, C. J. Basten, A. A. Myburg, Z.-B. Zeng, and R. R. Sederoff (2005)
Genetics 169, 2295-2303
   Abstract »    Full Text »    PDF »
Combined Genealogical, Mapping, and Expression Approaches to Identify Spontaneously Hypertensive Rat Hypertension Candidate Genes.
C. A. Hinojos, E. Boerwinkle, M. Fornage, and P. A. Doris (2005)
Hypertension 45, 698-704
   Abstract »    Full Text »    PDF »
On the utility of pooling biological samples in microarray experiments.
C. Kendziorski, R. A. Irizarry, K.-S. Chen, J. D. Haag, and M. N. Gould (2005)
PNAS 102, 4252-4257
   Abstract »    Full Text »    PDF »
Assessing natural variations in gene expression in humans by comparing with monozygotic twins using microarrays.
A. Sharma, V. K. Sharma, S. Horn-Saban, D. Lancet, S. Ramachandran, and S. K. Brahmachari (2005)
Physiol Genomics 21, 117-123
   Abstract »    Full Text »    PDF »
Allele-Specific Assay Reveals Functional Variation in the Chalcone Synthase Promoter of Arabidopsis thaliana That Is Compatible with Neutral Evolution.
J. de Meaux, U. Goebel, A. Pop, and T. Mitchell-Olds (2005)
PLANT CELL 17, 676-690
   Abstract »    Full Text »    PDF »
Comparative Analyses Reveal a Complex History of Molecular Evolution for Human MYH16.
G. H. Perry, B. C. Verrelli, and A. C. Stone (2005)
Mol. Biol. Evol. 22, 379-382
   Abstract »    Full Text »    PDF »
Genomic insights that advance the species definition for prokaryotes.
K. T. Konstantinidis and J. M. Tiedje (2005)
PNAS 102, 2567-2572
   Abstract »    Full Text »    PDF »
From the Cover: Conserved patterns of protein interaction in multiple species.
R. Sharan, S. Suthram, R. M. Kelley, T. Kuhn, S. McCuine, P. Uetz, T. Sittler, R. M. Karp, and T. Ideker (2005)
PNAS 102, 1974-1979
   Abstract »    Full Text »    PDF »
Selection-driven transcriptome polymorphism in Escherichia coli/Shigella species.
T. Le Gall, P. Darlu, P. Escobar-Paramo, B. Picard, and E. Denamur (2005)
Genome Res. 15, 260-268
   Abstract »    Full Text »    PDF »
Superiority of network motifs over optimal networks and an application to the revelation of gene network evolution.
S. Ott, A. Hansen, S.-Y. Kim, and S. Miyano (2005)
Bioinformatics 21, 227-238
   Abstract »    Full Text »    PDF »
Sperm Competitive Ability in Drosophila melanogaster Associated With Variation in Male Reproductive Proteins.
A. C. Fiumera, B. L. Dumont, and A. G. Clark (2005)
Genetics 169, 243-257
   Abstract »    Full Text »    PDF »
Positive selection on the human genome.
E. J. Vallender and B. T. Lahn (2004)
Hum. Mol. Genet. 13, R245-R254
   Abstract »    Full Text »    PDF »
Allele-specific gene expression differences in humans.
P. R. Buckland (2004)
Hum. Mol. Genet. 13, R255-R260
   Abstract »    Full Text »    PDF »
Genome-Wide Transcriptional Profiles Are Consistent with Functional Specialization of the Extraocular Muscle Layers.
S. Khanna, G. Cheng, B. Gong, M. J. Mustari, and J. D. Porter (2004)
Invest. Ophthalmol. Vis. Sci. 45, 3055-3066
   Abstract »    Full Text »    PDF »
Regional Patterns of Gene Expression in Human and Chimpanzee Brains.
P. Khaitovich, B. Muetzel, X. She, M. Lachmann, I. Hellmann, J. Dietzsch, S. Steigele, H.-H. Do, G. Weiss, W. Enard, et al. (2004)
Genome Res. 14, 1462-1473
   Abstract »    Full Text »    PDF »
A method for cross-species gene expression analysis with high-density oligonucleotide arrays.
W. Ji, W. Zhou, K. Gregg, N. Yu, S. Davis, and S. Davis (2004)
Nucleic Acids Res. 32, e93
   Abstract »    Full Text »    PDF »
Methods for Transcriptional Profiling in Plants. Be Fruitful and Replicate.
B. C. Meyers, D. W. Galbraith, T. Nelson, and V. Agrawal (2004)
Plant Physiology 135, 637-652
   Full Text »    PDF »
Statistical Framework for Phylogenomic Analysis of Gene Family Expression Profiles.
X. Gu (2004)
Genetics 167, 531-542
   Abstract »    Full Text »    PDF »
Quantitative genetic variation: a post-modern view.
M. Farrall (2004)
Hum. Mol. Genet. 13, R1-7
   Abstract »    Full Text »    PDF »
Improving the sensitivity and specificity of gene expression analysis in highly related organisms through the use of electronic masks.
S. Nagpal, M. W. Karaman, M. M. Timmerman, V. V. Ho, B. L. Pike, and J. G. Hacia (2004)
Nucleic Acids Res. 32, e51
   Abstract »    Full Text »    PDF »
Systematic changes in gene expression in postmortem human brains associated with tissue pH and terminal medical conditions.
J. Z. Li, M. P. Vawter, D. M. Walsh, H. Tomita, S. J. Evans, P. V. Choudary, J. F. Lopez, A. Avelar, V. Shokoohi, T. Chung, et al. (2004)
Hum. Mol. Genet. 13, 609-616
   Abstract »    Full Text »    PDF »
Unique gene expression signatures of independently-derived human embryonic stem cell lines.
M. J. Abeyta, A. T. Clark, R. T. Rodriguez, M. S. Bodnar, R. A. R. Pera, and M. T. Firpo (2004)
Hum. Mol. Genet. 13, 601-608
   Abstract »    Full Text »    PDF »
Sister grouping of chimpanzees and humans as revealed by genome-wide phylogenetic analysis of brain gene expression profiles.
M. Uddin, D. E. Wildman, G. Liu, W. Xu, R. M. Johnson, P. R. Hof, G. Kapatos, L. I. Grossman, and M. Goodman (2004)
PNAS 101, 2957-2962
   Abstract »    Full Text »    PDF »
Human-specific Regulation of {alpha}2-6-linked Sialic Acids.
P. Gagneux, M. Cheriyan, N. Hurtado-Ziola, E. C. M. B. van der Linden, D. Anderson, H. McClure, A. Varki, and N. M. Varki (2003)
J. Biol. Chem. 278, 48245-48250
   Abstract »    Full Text »    PDF »
Gene expression variation in the adult human retina.
I. Chowers, D. Liu, R. H. Farkas, T. L. Gunatilaka, A. S. Hackam, S. L. Bernstein, P. A. Campochiaro, G. Parmigiani, and D. J. Zack (2003)
Hum. Mol. Genet. 12, 2881-2893
   Abstract »    Full Text »    PDF »
Elevated gene expression levels distinguish human from non-human primate brains.
M. Caceres, J. Lachuer, M. A. Zapala, J. C. Redmond, L. Kudo, D. H. Geschwind, D. J. Lockhart, T. M. Preuss, and C. Barlow (2003)
PNAS 100, 13030-13035
   Abstract »    Full Text »    PDF »
Mixed-Model Reanalysis of Primate Data Suggests Tissue and Species Biases in Oligonucleotide-Based Gene Expression Profiles.
W.-P. Hsieh, T.-M. Chu, R. D. Wolfinger, and G. Gibson (2003)
Genetics 165, 747-757
   Abstract »    Full Text »    PDF »
Comprehensive Evaluation of the Extraocular Muscle Critical Period by Expression Profiling in the Dark-Reared Rat and Monocularly Deprived Monkey.
G. Cheng, M. J. Mustari, S. Khanna, and J. D. Porter (2003)
Invest. Ophthalmol. Vis. Sci. 44, 3842-3855
   Abstract »    Full Text »    PDF »
The Evolution of Transcriptional Regulation in Eukaryotes.
G. A. Wray, M. W. Hahn, E. Abouheif, J. P. Balhoff, M. Pizer, M. V. Rockman, and L. A. Romano (2003)
Mol. Biol. Evol. 20, 1377-1419
   Abstract »    Full Text »    PDF »
Comparative Analysis of Gene-Expression Patterns in Human and African Great Ape Cultured Fibroblasts.
M. W. Karaman, M. L. Houck, L. G. Chemnick, S. Nagpal, D. Chawannakul, D. Sudano, B. L. Pike, V. V. Ho, O. A. Ryder, and J. G. Hacia (2003)
Genome Res. 13, 1619-1630
   Abstract »    Full Text »    PDF »
Comparative sequencing of human and chimpanzee MHC class I regions unveils insertions/deletions as the major path to genomic divergence.
T. Anzai, T. Shiina, N. Kimura, K. Yanagiya, S. Kohara, A. Shigenari, T. Yamagata, J. K. Kulski, T. K. Naruse, Y. Fujimori, et al. (2003)
PNAS 100, 7708-7713
   Abstract »    Full Text »    PDF »
Selection on Human Genes as Revealed by Comparisons to Chimpanzee cDNA.
I. Hellmann, S. Zollner, W. Enard, I. Ebersberger, B. Nickel, and S. Paabo (2003)
Genome Res. 13, 831-837
   Abstract »    Full Text »    PDF »
A Promoter that Acquired p53 Responsiveness During Primate Evolution.
A. Contente, H. Zischler, A. Einspanier, and M. Dobbelstein (2003)
Cancer Res. 63, 1756-1758
   Abstract »    Full Text »    PDF »
Large-Scale Variation Among Human and Great Ape Genomes Determined by Array Comparative Genomic Hybridization.
D. P. Locke, R. Segraves, L. Carbone, N. Archidiacono, D. G. Albertson, D. Pinkel, and E. E. Eichler (2003)
Genome Res. 13, 347-357
   Abstract »    Full Text »    PDF »