Human-specific transcriptional networks in the brain

Neuron. 2012 Aug 23;75(4):601-17. doi: 10.1016/j.neuron.2012.05.034.

Abstract

Understanding human-specific patterns of brain gene expression and regulation can provide key insights into human brain evolution and speciation. Here, we use next-generation sequencing, and Illumina and Affymetrix microarray platforms, to compare the transcriptome of human, chimpanzee, and macaque telencephalon. Our analysis reveals a predominance of genes differentially expressed within human frontal lobe and a striking increase in transcriptional complexity specific to the human lineage in the frontal lobe. In contrast, caudate nucleus gene expression is highly conserved. We also identify gene coexpression signatures related to either neuronal processes or neuropsychiatric diseases, including a human-specific module with CLOCK as its hub gene and another module enriched for neuronal morphological processes and genes coexpressed with FOXP2, a gene important for language evolution. These data demonstrate that transcriptional networks have undergone evolutionary remodeling even within a given brain region, providing a window through which to view the foundation of uniquely human cognitive capacities.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / anatomy & histology*
  • Brain / metabolism*
  • CLOCK Proteins / genetics
  • CLOCK Proteins / metabolism
  • Evolution, Molecular
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism
  • Gene Expression / physiology*
  • Gene Expression Profiling
  • Gene Regulatory Networks / genetics
  • Humans
  • Macaca
  • Mental Disorders / genetics
  • Oligonucleotide Array Sequence Analysis
  • Pan troglodytes
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • FOXP2 protein, human
  • Forkhead Transcription Factors
  • Transcription Factors
  • CLOCK Proteins

Associated data

  • GEO/GSE33588