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MicroRNA-driven developmental remodeling in the brain distinguishes humans from other primates

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Item Type:Article
Title:MicroRNA-driven developmental remodeling in the brain distinguishes humans from other primates
Creators Name:Somel, M. and Liu, X. and Tang, L. and Yan, Z. and Hu, H. and Guo, S. and Jiang, X. and Zhang, X. and Xu, G. and Xie, G. and Li, N. and Hu, Y. and Chen, W. and Paeaebo, S. and Khaitovich, P.
Abstract:While multiple studies have reported the accelerated evolution of brain gene expression in the human lineage, the mechanisms underlying such changes are unknown. Here, we address this issue from a developmental perspective, by analyzing mRNA and microRNA (miRNA) expression in two brain regions within macaques, chimpanzees, and humans throughout their lifespan. We find that constitutive gene expression divergence (species differences independent of age) is comparable between humans and chimpanzees. However, humans display a 3-5 times faster evolutionary rate in divergence of developmental patterns, compared to chimpanzees. Such accelerated evolution of human brain developmental patterns (i) cannot be explained by life-history changes among species, (ii) is twice as pronounced in the prefrontal cortex than the cerebellum, (iii) preferentially affects neuron-related genes, and (iv) unlike constitutive divergence does not depend on cis-regulatory changes, but might be driven by human-specific changes in expression of trans-acting regulators. We show that developmental profiles of miRNAs, as well as their target genes, show the fastest rates of human-specific evolutionary change, and using a combination of computational and experimental methods, we identify miR-92a, miR-454, and miR-320b as possible regulators of human-specific neural development. Our results suggest that different mechanisms underlie adaptive and neutral transcriptome divergence, and that changes in the expression of a few key regulators may have been a major driving force behind rapid evolution of the human brain.
Keywords:Brain, Cerebellum, Computational Biology, Developmental Gene Expression Regulation, Gene Expression Profiling, Messenger RNA, MicroRNAs, Molecular Evolution, Nerve Tissue Proteins, Neurogenesis, Neurons, Oligonucleotide Array Sequence Analysis, Organ Specificity, Prefrontal Cortex, Species Specificity, Tissue Banks, Animals, Macaca mulatta, Pan troglodytes
Source:PLoS Biology
ISSN:1544-9173
Publisher:Public Library of Science (U.S.A.)
Volume:9
Number:12
Page Range:e1001214
Date:December 2011
Official Publication:https://doi.org/10.1371/journal.pbio.1001214
PubMed:View item in PubMed

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