Diferenças em padrões de expressão de gene em humanos e chimpanzés definem uma rede evolutiva de fatores de transcrição no cérebro

Differences in human and chimpanzee gene expression patterns define an evolving network of transcription factors in brain

Katja Nowick a,b, Tim Gernat a,b, Eivind Almaas c and Lisa Stubbs a,b,1

- Author Affiliations

aInstitute for Genomic Biology and

bDepartment of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801; and

cDepartment of Biotechnology, Norwegian University of Science and Technology, N-7491 Trondheim, Norway

Communicated by Gene E. Robinson, University of Illinois at Urbana-Champaign, Urbana, IL, October 4, 2009 (received for review July 7, 2009)

Abstract

Humans differ from other primates by marked differences in cognitive abilities and a significantly larger brain. These differences correlate with metabolic changes, as evidenced by the relative up-regulation of energy-related genes and metabolites in human brain. While the mechanisms underlying these evolutionary changes have not been elucidated, altered activities of key transcription factors (TFs) could play a pivotal role. To assess this possibility, we analyzed microarray data from five tissues from humans and chimpanzees. We identified 90 TF genes with significantly different expression levels in human and chimpanzee brain among which the rapidly evolving KRAB-zinc finger genes are markedly over-represented. The differentially expressed TFs cluster within a robust regulatory network consisting of two distinct but interlinked modules, one strongly associated with energy metabolism functions, and the other with transcription, vesicular transport, and ubiquitination. Our results suggest that concerted changes in a relatively small number of interacting TFs may coordinate major gene expression differences in human and chimpanzee brain.

comparative transcriptomics KRAB-zinc finger genes primate evolution gene regulatory network evolution

Footnotes

1To whom correspondence should be addressed at: Institute for Genomic Biology, University of Illinois at Urbana-Champaign, 1206 West Gregory Drive, Urbana, IL 61801. E-mail: ljstubbs@illinois.edu

Author contributions: K.N. and L.S. designed research; K.N. performed research; T.G. and E.A. contributed new reagents/analytic tools; K.N., T.G., E.A., and L.S. analyzed data; and K.N. and L.S. wrote the paper.

The authors declare no conflict of interest.

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