Human-Specific Transcriptional Networks in the Brain

• Type of Material: Article
• Authors: Genevieve Konopka, University of California; Tara Friedrich, University of California; Jeremy Davis-Turak, University of California; Kellen Winden, University of California; Michael C. Oldham, University of California; Fuying Gao, University of California; Leslie Chen, University of California; Guang-Zhong Wang, University of Texas; Rui Luo, University of California; Todd M Preuss, Emory University; Daniel H. Geschwind, University of California
• Language: English
• Date: 2012-08-23
• Publisher: Elsevier (Cell Press)
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2012 Elsevier Inc. Published by Elsevier Inc.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.neuron.2012.05.034
• Title of Journal or Parent Work: Neuron
• ISSN: 0896-6273
• Volume: 75
• Issue: 4
• Start Page: 601
• End Page: 617
• Grant/Funding Information: 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).
• Research Categories: Biology, Genetics; Biology, Neuroscience

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.