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Author Notes:

Corresponding authors: Daniel H. Geschwind, MD, PhD Tel: (310) 794-7537 ude.alcu@ghd Genevieve Konopka, PhD Tel: (214) 648-5135; Genevieve.Konopka@utsouthwestern.edu

Contributions 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 non-human primate samples.

G.K. and D.H.G. wrote the manuscript.

All authors discussed the results and commented on the manuscript.

We thank Dr. Giovanni Coppola for providing code for microarray and WGCNA analyses and Lauren Kawaguchi for lab management.

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.

Gene expression data have been deposited in the NCBI Gene Expression Omnibus (GEO; http://www.ncbi.nlm.nih.gov/geo) and are accessible using GEO series accession number GSE33588.

Subjects:

Research Funding:

This work is supported by grants from the NIMH (R37MH060233) (DHG) and (R00MH090238) (GK), a NARSAD Young Investigator Award (GK), the National Center for Research Resources (RR00165) and Office of Research Infrastructure Programs/OD (P51OD11132), and a James S. McDonnell Foundation grant (JSMF 21002093) (TMP, DHG).

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).

Human-Specific Transcriptional Networks in the Brain

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Journal Title:

Neuron

Volume:

Volume 75, Number 4

Publisher:

, Pages 601-617

Type of Work:

Article | Post-print: After Peer Review

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 co-expression 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 co-expressed 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 new window through which to view the foundation of uniquely human cognitive capacities.

Copyright information:

© 2012 Elsevier Inc. Published by Elsevier Inc.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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