A human-specific de novo protein-coding gene associated with human brain functions

Chuan Yun Li, Yong Zhang, Zhanbo Wang, Yan Zhang, Chunmei Cao, Ping Wu Zhang, Shu Juan Lu, Xiao Mo Li, Quan Yu, Xiaofeng Zheng, Quan Du, George R. Uhl, Qing Rong Liu, Liping Wei

Research output: Contribution to journalArticle

Abstract

To understand whether any human-specific new genes may be associated with human brain functions, we computationally screened the genetic vulnerable factors identified through Genome-Wide Association Studies and linkage analyses of nicotine addiction and found one human-specific de novo protein-coding gene, FLJ33706 (alternative gene symbol C20orf203). Cross-species analysis revealed interesting evolutionary paths of how this gene had originated from noncoding DNA sequences: insertion of repeat elements especially Alu contributed to the formation of the first coding exon and six standard splice junctions on the branch leading to humans and chimpanzees, and two subsequent substitutions in the human lineage escaped two stop codons and created an open reading frame of 194 amino acids. We experimentally verified FLJ33706's mRNA and protein expression in the brain. Real-Time PCR in multiple tissues demonstrated that FLJ33706 was most abundantly expressed in brain. Human polymorphism data suggested that FLJ33706 encodes a protein under purifying selection. A specifically designed antibody detected its protein expression across human cortex, cerebellum and midbrain. Immunohistochemistry study in normal human brain cortex revealed the localization of FLJ33706 protein in neurons. Elevated expressions of FLJ33706 were detected in Alzheimer's brain samples, suggesting the role of this novel gene in human-specific pathogenesis of Alzheimer's disease. FLJ33706 provided the strongest evidence so far that human-specific de novo genes can have protein-coding potential and differential protein expression, and be involved in human brain functions.

Original languageEnglish (US)
JournalPLoS computational biology
Volume6
Issue number3
DOIs
StatePublished - Mar 1 2010

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Modeling and Simulation
  • Ecology
  • Molecular Biology
  • Genetics
  • Cellular and Molecular Neuroscience
  • Computational Theory and Mathematics

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  • Cite this

    Li, C. Y., Zhang, Y., Wang, Z., Zhang, Y., Cao, C., Zhang, P. W., Lu, S. J., Li, X. M., Yu, Q., Zheng, X., Du, Q., Uhl, G. R., Liu, Q. R., & Wei, L. (2010). A human-specific de novo protein-coding gene associated with human brain functions. PLoS computational biology, 6(3). https://doi.org/10.1371/journal.pcbi.1000734