MicroRNA-Driven Developmental Remodeling in the Brain Distinguishes Humans from Other Primates

Massey University, New Zealand
PLoS Biology (Impact Factor: 11.77). 12/2011; 9(12):e1001214. DOI: 10.1371/journal.pbio.1001214
Source: PubMed

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.

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Available from: Augix Guohua Xu, Aug 21, 2015
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    • "We found differential expression of several microRNAs in the matched tissue comparison; however, this approach did not indicate how the expression levels relate to normal cortical tissue from non-TSC subjects. To address that question, we utilized microRNA data from a postmortem (PM) study of primate brain tissue that included samples from human, chimpanzee, and macaque (Somel et al. 2011). The study investigated microRNA expression in prefrontal cortex and cerebellar cortex from subjects representing a wide range of ages. "
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    Cerebral Cortex 12/2014; DOI:10.1093/cercor/bhu276 · 8.67 Impact Factor
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    • "BCAN and GRIN3A show human-specific expression changes in the prefrontal cortex when compared with chimpanzee and rhesus macaque, which is consistent with our findings (Liu et al., 2012). Human-specific expression changes may also be explained by trans-factors (e.g., transcription factors or microRNAs) (Somel et al., 2011). The promoter region of ANKRD57 showed statistically significant evidence of negative selection (v 2 5 6.239, df 5 1, P 5 0.012), as evidenced by a high neutrality index (NI515.3). "
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    • "Meaningful parallel variation may be most simple and direct to observe in proteins, but variation in regulatory regions is likely to be more plentiful and perhaps more important for understanding complex disease. This extends to variation in microRNAs, the role of which, so far, has only been hinted at (Hu et al. 2011; Somel et al. 2011). Perhaps the most promising and interesting future avenue along these lines, however, is in CNVs. "
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