Brain Evolution at a Distance
Gene expression controlled from afar may have spurred the spurt in brain evolution that led to modern humans.
By Hannah Waters | December 6, 2011
Scientists and philosophers alike have long grasped for the essence that makes humans human, and one answer lies in the brain. Specifically, human brains express genes in different patterns than those of related species, but what causes those changes is unknown. Comparing gene expression in three primate species—human, chimpanzee, and the rhesus macaque—across post-natal development, researchers, publishing today (December 6) in PLoS Biology, found that the most drastic expression changes are found in genes that are controlled at a distance by trans regulators, instead of locally by cis regulators.
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“The authors here found a new explanation for how this evolution of the advanced human brain occurred at the molecular level,” said Henrik Kaessmann, who studies genomic evolution at the University of Lausanne in Switzerland and was not involved in the research. “It’s a very interesting message: that functionally relevant changes tend to be more trans driven.”
Despite the minute genetic differences between human brains and their primate relatives, Homo sapiens cognitive ability is significantly more advanced, enabling us to “make complicated tools, come up with complicated culture and colonize the world,” said lead author Mehmet Somel, a postdoc studying human evolutionary genomics at the University of California, Berkeley. Because humans spend more than a decade developing into adults and learning, far more than the two or three years of chimpanzee adolescence, researchers have long suspected that developmental genes are involved in human brain evolution. “And the idea that brain gene expression profiles might be different between species was proposed 40 years ago,” Somel added.
To explore both of these ideas, Somel and his colleagues at the Max Planck Institute and the Chinese Academy of Sciences observed gene expression changes throughout postnatal development in humans, chimpanzees, and rhesus macaques. They analyzed the differential expression of around 12,000 genes in two brain regions—the prefrontal cortex and cerebellar cortex, each of which have been put forth as the focal point of human brain evolution. They found significant differences between species, as well as variation among the different aged organisms of a species, but they also found variation in gene expression that couldn’t be simply explained by either of these two factors. It seemed that there were some genes that were not only differentially expressed over the course of development, but also at a different rate by each species.
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Read more here/Leia mais aqui: The Scientist
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MicroRNA-Driven Developmental Remodeling in the Brain Distinguishes Humans from Other Primates
Mehmet Somel1,2#¤, Xiling Liu1#, Lin Tang1,Zheng Yan1, Haiyang Hu1, Song Guo1, Xi Jiang1,Xiaoyu Zhang1, Guohua Xu1,2, Gangcai Xie1,3, Na Li4, Yuhui Hu4, Wei Chen4,5, Svante Pääbo2*,Philipp Khaitovich1,2*
1 Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Chinese Academy of Sciences, Shanghai, China, 2 Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany, 3 Graduate School of Chinese Academy of Sciences, Beijing, China, 4 Max Delbrück Center for Molecular Medicine, Berlin-Buch, Germany, 5 Max Planck Institute for Molecular Genetics, Berlin, Germany
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 oncis-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.
Author Summary
Species evolution is often depicted as a slow and continuous process punctuated by rapid changes. One example of the latter is the evolution of human cognition–emergence of an exceedingly complex phenotype within a few million years. What genetic mechanisms might have driven this process? Nearly 40 years ago, it was proposed that human-specific gene expression changes, rather than changes in protein sequence, might underlie human cognitive evolution. Here we compare gene expression throughout postnatal brain development in humans, chimpanzees, and macaques. We find that simple changes in gene expression levels, plausibly driven by mutations in cis-regulatory elements, accumulate at similar rates in all three evolutionary lineages. What sharply distinguishes humans from other species is change in the timing and shape of developmental expression patterns. This is particularly pronounced in the prefrontal cortex, where 4-fold more genes show more human-specific developmental changes than chimpanzee-specific ones. Notably, our results indicate that this massive developmental remodeling of the human cortex, which affects hundreds of genes, might be driven by expression changes of only a few key regulators, such as microRNAs. Genes affected by this remodeling are preferentially associated with neural activity, thereby suggesting a link to the evolution of human cognition.
Citation: Somel M, Liu X, Tang L, Yan Z, Hu H, et al. (2011) MicroRNA-Driven Developmental Remodeling in the Brain Distinguishes Humans from Other Primates. PLoS Biol 9(12): e1001214. doi:10.1371/journal.pbio.1001214
Academic Editor: David Penny, Massey University, New Zealand
Received: May 22, 2011; Accepted: October 27, 2011; Published: December 6, 2011
Copyright: © 2011 Somel et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: The study was funded by the Ministry of Science and Technology of the People's Republic of China (grant no. 2007CB947004), Chinese Academy of Sciences (grant no. KSCX2-YW-R-094 and KSCX2-YW-R-251), the Shanghai Institutes for Biological Sciences (grant no. 2008KIT104), National Science Foundation of China research grant (grant no. 31010022 & 31050110128), the Max Planck-Society, and the Bundesministerum fuer Bildung und Forschung. MS was supported by fellowships from the Chinese Academy of Sciences (2009Y2BS12) and European Molecular Biology Organization (EMBO ALTF 1475–2010). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
* E-mail: paabo@eva.mpg.de (SP); khaitovich@eva.mpg.de (PK)
# These authors contributed equally to this work.
¤ Current address: Department of Integrative Biology, University of California–Berkeley, Berkeley, California, United States of America
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