Multi-species microarrays reveal the effect of sequence divergence on gene expression profiles

  1. Yoav Gilad1,4,
  2. Scott A. Rifkin1,2,
  3. Paul Bertone3,
  4. Mark Gerstein3, and
  5. Kevin P. White1,2,4
  1. 1 Yale University School of Medicine, Department of Genetics, Yale University, New Haven, Connecticut 06520, USA
  2. 2 Ecology and Evolutionary Biology Department, Yale University, New Haven, Connecticut 06520, USA
  3. 3 Molecular Biophysics and Biochemistry Department, Yale University, New Haven, Connecticut 06520, USA

Abstract

Interspecies comparisons of gene expression levels will increase our understanding of the evolution of transcriptional mechanisms and help to identify targets of natural selection. This approach holds particular promise for apes, as many human-specific adaptations are thought to result from differences in gene expression rather than in coding sequence. To date, however, all studies directly comparing interspecies gene expression have been performed on single-species arrays, so that it has been impossible to distinguish differential hybridization due to sequence mismatches from underlying expression differences. To evaluate the severity of this potential problem, we constructed a new multiprimate cDNA array using probes from human, chimpanzee, orangutan, and rhesus. We find a large effect of sequence divergence on hybridization signal, even in the closest pair of species, human and chimpanzee. By comparing single-species array analyses with results from multispecies arrays, we examine how estimates of differential gene expression are affected by sequence divergence. Our results indicate that naive use of single-species arrays in direct interspecies comparisons can yield spurious results.

Footnotes

  • [Supplemental material is available online at www.genome.org. All expression data was submitted to the GEO database (http://www.ncbi.nlm.nih.gov/geo/) under the series GSE2009, with sample accession numbers GSM35572, GSM35573, GSM35574, GSM35575, GSM35576, GSM35577, GSM35578, GSM35579, GSM35580, GSM35581, GSM35582, GSM35583, GSM35584, GSM35585, GSM35586, GSM35587. The following individuals kindly provided reagents, samples, or unpublished information as indicated in the paper: S. Pääbo and P. Khaitovich.]

  • Article and publication are at http://www.genome.org/cgi/doi/10.1101/gr.3335705.

  • 4 Corresponding authors. E-mail Yoav.Gilad{at}yale.edu; fax (203) 785-6333. E-mail Kevin.White{at}yale.edu; fax (203) 785-6333.

    • Accepted February 2, 2005.
    • Received October 8, 2004.
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