TY - JOUR
T1 - Human-Specific Transcriptional Networks in the Brain
AU - Konopka, Genevieve
AU - Friedrich, Tara
AU - Davis-Turak, Jeremy
AU - Winden, Kellen
AU - Oldham, Michael C.
AU - Gao, Fuying
AU - Chen, Leslie
AU - Wang, Guang Zhong
AU - Luo, Rui
AU - Preuss, Todd M.
AU - Geschwind, Daniel H.
N1 - Funding Information:
We thank Dr. Giovanni Coppola for providing code for microarray and WGCNA analyses and Lauren Kawaguchi for laboratory management. This work is supported by grants from the NIMH (R37MH060233) (D.H.G.) and (R00MH090238) (G.K.), a NARSAD Young Investigator Award (G.K.), the National Center for Research Resources (RR00165) and Office of Research Infrastructure Programs/OD (P51OD11132), and a James S. McDonnell Foundation grant (JSMF 21002093) (T.M.P., D.H.G.). Human tissue was obtained from the NICHD Brain and Tissue Bank for Developmental Disorders at the University of Maryland (NICHD contract numbers N01-HD-4-3368 and N01-HD-4-3383). The role of the NICHD Brain and Tissue Bank is to distribute tissue and therefore cannot endorse the studies performed or the interpretation of results. G.K., M.O., T.M.P., and D.H.G. conceived the project. G.K. and L.C. conducted experiments. G.K., T.F., J.D.-T., K.W., M.O., F.G., G.-Z.W., and R.L. analyzed data. T.M.P. performed IHC and tissue dissections and provided nonhuman primate samples. G.K. and D.H.G. wrote the manuscript. All authors discussed the results and commented on the manuscript.
PY - 2012/8/23
Y1 - 2012/8/23
N2 - 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.
AB - 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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U2 - 10.1016/j.neuron.2012.05.034
DO - 10.1016/j.neuron.2012.05.034
M3 - Article
C2 - 22920253
AN - SCOPUS:84865374280
SN - 0896-6273
VL - 75
SP - 601
EP - 617
JO - Neuron
JF - Neuron
IS - 4
ER -