http://dx.doi.org/10.1371/journal.pbio.0050013 * Published December 26, 2006 - RESEARCH ARTICLE Rate of Evolution in Brain-Expressed Genes in Humans and Other Primates Wang HY, Chien HC, Osada N, Hashimoto K, Sugano S, et al. PLoS Biology Vol. 5, No. 2, e13 doi:10.1371/journal.pbio.0050013 RESEARCH ARTICLE Open Access Everything we publish is freely available online throughout the world, for you to read, download, copy, distribute, and use (with attribution) any way you wish. No permission required. Read a detailed definition of open access. Rate of Evolution in Brain-Expressed Genes in Humans and Other Primates Hurng-Yi Wang1,2?, Huan-Chieh Chien1, Naoki Osada3, Katsuyuki Hashimoto4, Sumio Sugano5, Takashi Gojobori6, Chen-Kung Chou7, Shih-Feng Tsai8, Chung-I Wu2*, C.-K. James Shen1* 1 Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan, 2 Department of Ecology and Evolution, University of Chicago, Chicago, Illinois, United States of America, 3 Division of Biomedical Research Resources, National Institute of Biomedical Innovation, Osaka, Japan, 4 Division of Genetic Resources, National Institute of Infectious Diseases, Tokyo, Japan, 5 Laboratory of Functional Genomics, Department of Medical Genome Sciences, Graduate School of Frontier Sciences, University of Tokyo, Tokyo, Japan, 6 Center of Information Biology, National Institute of Genetics, Mishima, Japan, 7 Department of Life Science, Chang Gung University, Tao-Yuan, Taiwan, 8 Division of Molecular and Genomic Medicine, National Health Research Institute, Miaoli, Taiwan Brain-expressed genes are known to evolve slowly in mammals. Nevertheless, since brains of higher primates have evolved rapidly, one might expect acceleration in DNA sequence evolution in their brain-expressed genes. In this study, we carried out full-length cDNA sequencing on the brain transcriptome of an Old World monkey (OWM) and then conducted three-way comparisons among (i) mouse, OWM, and human, and (ii) OWM, chimpanzee, and human. Although brain-expressed genes indeed appear to evolve more rapidly in species with more advanced brains (apes > OWM > mouse), a similar lineage effect is observable for most other genes. The broad inclusion of genes in the reference set to represent the genomic average is therefore critical to this type of analysis. Calibrated against the genomic average, the rate of evolution among brain-expressed genes is probably lower (or at most equal) in humans than in chimpanzee and OWM. Interestingly, the trend of slow evolution in coding sequence is no less pronounced among brain-specific genes, vis-a`-vis brain-expressed genes in general. The human brain may thus differ from those of our close relatives in two opposite directions: (i) faster evolution in gene expression, and (ii) a likely slowdown in the evolution of protein sequences. Possible explanations and hypotheses are discussed. Funding. This research was supported by the Academia Sinica and the National Science Council, Taiwan; the Ministry of the Health and Welfare, Japan; and US Public of Health (NIH) Grants. Competing interests. The authors have declared that no competing interests exist. Academic Editor: Kenneth Wolfe, University of Dublin, Ireland Citation: Wang HY, Chien HC, Osada N, Hashimoto K, Sugano S, et al. (2007) Rate of Evolution in Brain-Expressed Genes in Humans and Other Primates. PLoS Biol 5(2): e13 DOI: 10.1371/journal.pbio.0050013 Received: May 23, 2006; Accepted: November 10, 2006; Published: December 26, 2006 Copyright: (c) 2007 Wang 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. Abbreviations: CDS, coding sequence; Consortium, Chimpanzee Sequencing and Analysis Consortium; Ka, number of substitutions per site for nonsynonymous sites; Ks, number of substitutions per site for synonymous sites; OWM, Old World monkey * To whom correspondence should be addressed. E-mail: [email protected] (CIW); [email protected] (CKJS) ? Current address: Graduate Institute of Clinical Medicine, National Taiwan University, Taipei, Taiwan Author Summary Whether comparing morphology or cognitive ability, it is clear that the human brain has evolved rapidly relative to that of other primates. But the extent to which genes expressed in the brain also reflect this overall pattern is unclear. To address this question, it's necessary to measure any variations in the DNA sequences of these genes between human and chimpanzee. And, to do this as accurately as possible, it's also important to require an appropriate reference group to act as a benchmark against which the differences can be measured. We therefore compared publicly available genomic sequences of chimps and humans with complementary DNA sequences of several thousand genes expressed in the brain of another closely related primate—the macaque, an Old World monkey—as well as the more distantly related mouse. Our analyses of the rates of protein evolution in these species suggest that genes expressed in the human brain have in fact slowed down in their evolution since the split between human and chimpanzee, contrary to some previously published reports. We suggest that advanced brains are driven primarily by the increasing complexity in the network of gene interactions. As a result, brain-expressed genes are constrained in their sequence evolution, although their expression levels may change rapidly. -- ┌─────◆ＫＫＣＩＴＹ◆─────┐▇─┐ 优质连线服务隆/重/豋/场!! │ bbs.kkcity.com.tw │┴ └─▇ KKADSL 带你环游全世界 └──《From:143.48.8.154 》──┘ KKADSL ┴ http://adsl.kkcity.com.tw --