Detecting positive darwinian selection in brain-expressed genes during human evolution  

作　　者：QI XueBin YANG Su ZHENG HongKun WANG YinQiu LIAO ChengHong LIU Ying CHEN XiaoHua SHI Hong YU xiaoJing Alice A. LIN Luca L. CAVALLI-SFORZA WANG Jun SU Bing 

机构地区：[1]Key Laboratory of Cellular and Molecular Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223 China [2]Kunming Primate Research Center, Chinese Academy of Sciences, Kunming 650223, China [3]Beijing Institute of Genomics of Chinese Academy of Sciences, Beijing Genomics Institute, Beijing Proteomics Institute, Beijing 101300, China [4]Department of Genetics, Stanford University, Stanford, USA [5]Graduate School of the Chinese Academy of Sciences, Beijing 100039, China [6]The Institute of Human Genetics, University of Aarhus, Aarhus C, DK-8000, Denmark [7]Department of Biochemistry and Molecular Biology, University of Southem Denmark, Odense M, DK-5230, Denmark

出　　处：《Chinese Science Bulletin》2007年第3期324-335,共12页

基　　金：the Chinese Academy of Sciences (Grant Nos. KSCX2-SW-121 and GJHZ0518);the National Natural Science Foundation of China (Grant Nos. 30370755, 30440018, 30525028, 90208019, 90403130 and 30221004);the National 973 Project of China (Grant No. 2006CB701506);the Post-doctoral Fellowship of China (Grant No. 2005038271);Ministry of Science and Technology under program (Grant No. CNGI-04-15-7A);the Natural Science Foundation of Yunnan Province of China, China National Grid;Danish Platform for Integrative Biology and Ole R■mer grants from the Danish Natural Science Research Council

摘　　要：To understand the genetic basis that underlies the phenotypic divergence between human and non- human primates, we screened a total of 7176 protein-coding genes expressed in the human brain and compared them with the chimpanzee orthologs to identify genes that show evidence of rapid evolution in the human lineage. Our results showed that the nonsynonymous/synonymous substitution (Ka/Ks) ratio for genes expressed in the brain of human and chimpanzee is 0.3854, suggesting that the brain-expressed genes are under functional constraint. The X-linked human brain-expressed genes evolved more rapidly than autosomal ones. We further dissected the molecular evolutionary patterns of 34 candidate genes by sequencing representative primate species to identify lineage-specific adaptive evolution. Fifteen out of the 34 candidate genes showed evidence of positive Darwinian selection in human and/or chimpanzee lineages. These genes are predicted to play diverse functional roles in em- bryonic development, spermatogenesis and male fertility, signal transduction, sensory nociception, and neural function. This study together with others demonstrated the usefulness and power of phy- logenetic comparison of multiple closely related species in detecting lineage-specific adaptive evolu- tion, and the identification of the positively selected brain-expressed genes may add new knowledge to the understanding of molecular mechanism of human origin.To understand the genetic basis that underlies the phenotypic divergence between human end non- human primates, we screened e total of 7176 protein-coding genes expressed in the human brain end compared them with the chimpanzee orthologs to identify genes that show evidence of rapid evolution in the human lineage. Our results showed that the nonsynonymous/synonymous substitution （Ka/Ka） ratio for genes expressed in the brain of human end chimpanzee is 0.3854, suggesting that the brain-expressed genes ere under functional constraint. The X-linked human brein-exprsseed genes evolved more rapidly than eutosomel ones. We further dissected the molecular evolutionary patterns of 34 candidate genes by sequencing representative primate species to identify lineage-specific adaptive evolution. Fifteen out of the 34 candidate genes showed evidence of positive Darwinian selection in human end/or chimpanzee lineages. These genes ere predicted to play diverse functional roles in embryonic development, spermetogenesis and male fertility, signal trensduction, sensory nociception, end neural function. This study together with others demonstrated the usefulness end power of phylogenetic comparison of multiple closely related species in detecting lineage-specific adaptive evolution, and the identification of the positively selected brain-expressed genes may add new knowledge to the understanding of molecular mechanism of human origin.

关 键 词：人类进化 适应性进化 正向选择 人脑表达基因 检测 人科动物 达尔文学说 

分 类 号：Q981.1[天文地球—古生物学与地层学] Q111.21[生物学—人类学]