Human-Specific Transcriptional Networks in the Brain

Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Neuron (Impact Factor: 15.05). 08/2012; 75(4):601-17. DOI: 10.1016/j.neuron.2012.05.034
Source: PubMed


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.

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    • "Our HYP punches contained several hypothalamic nuclei (see Materials and methods and Fig. S1) in which genes may be differentially regulated. In networks that are built using samples collected from multiple, distinct brain regions or nuclei, modules that distinguish these individual nuclei or specific brain regions can be identified (Drnevich et al. 2012;Konopka et al. 2012;Oldham et al. 2006). We were unable to perform this type of analysis with our dataset because our network was built using one sample type (HYP). "
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    • "Although the composition of the post-synaptic density is well conserved among mammals (Bayés et al., 2010), the dynamic component of plasticity provided by mRNA and miRNA is quite divergent. Human transcription networks have evolved a complexity that drives species-specific gene expression in the pre-frontal (PFC) and frontal cortices (Konopka et al., 2012). "
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    • "Recent monumental attempts to decipher the transcriptome in the human brain have undoubtedly contributed to our anatomical understanding of the transcriptional network and disease-related changes in inaccessible tissues [4, 5]. Subsequent proteomic or metabolomic analyses will provide further crucial information in the near future. "
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