A Human-Specific De Novo Protein-Coding Gene Associated with Human Brain Functions
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{"title"=>"A Human-Specific De Novo Protein-Coding Gene Associated with Human Brain Functions", "type"=>"journal", "authors"=>[{"first_name"=>"Chuan-Yun", "last_name"=>"Li"}, {"first_name"=>"Yong", "last_name"=>"Zhang"}, {"first_name"=>"Zhanbo", "last_name"=>"Wang"}, {"first_name"=>"Yan", "last_name"=>"Zhang"}, {"first_name"=>"Chunmei", "last_name"=>"Cao"}, {"first_name"=>"Ping-Wu", "last_name"=>"Zhang"}, {"first_name"=>"Shu-Juan", "last_name"=>"Lu"}, {"first_name"=>"Xiao-Mo", "last_name"=>"Li"}, {"first_name"=>"Quan", "last_name"=>"Yu"}, {"first_name"=>"Xiaofeng", "last_name"=>"Zheng"}, {"first_name"=>"Quan", "last_name"=>"Du"}, {"first_name"=>"George R.", "last_name"=>"Uhl"}, {"first_name"=>"Qing-Rong", "last_name"=>"Liu"}, {"first_name"=>"Liping", "last_name"=>"Wei"}], "year"=>2010, "source"=>"PLoS Computational Biology", "identifiers"=>{"isbn"=>"1553-7358 (Electronic)\\n1553-734X (Linking)", "doi"=>"10.1371/journal.pcbi.1000734", "issn"=>"1553-7358", "pmid"=>"20376170"}, "id"=>"8f2fbe82-f481-3725-918a-809c2134570d", "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.", "link"=>"http://www.mendeley.com/research/humanspecific-novo-proteincoding-gene-associated-human-brain-functions-9", "reader_count"=>28, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>3, "Student > Doctoral Student"=>2, "Researcher"=>4, "Student > Ph. D. Student"=>9, "Student > Postgraduate"=>2, "Student > Master"=>3, "Other"=>2, "Student > Bachelor"=>1, "Professor"=>2}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>3, "Student > Doctoral Student"=>2, "Researcher"=>4, "Student > Ph. D. Student"=>9, "Student > Postgraduate"=>2, "Student > Master"=>3, "Other"=>2, "Student > Bachelor"=>1, "Professor"=>2}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>5, "Agricultural and Biological Sciences"=>21, "Psychology"=>2}, "reader_count_by_subdiscipline"=>{"Psychology"=>{"Psychology"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>21}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>5}}, "reader_count_by_country"=>{"Colombia"=>1, "Austria"=>1, "United States"=>1, "China"=>1, "Spain"=>1}, "group_count"=>3}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/856373"], "description"=>"<p>Data for the tracks ‘Spliced Human EST’ and ‘Human mRNA’ was extracted and assembled from UCSC Genome Browser. We re-sequenced all available mRNAs and spliced ESTs, shown in the track ‘Re-sequenced ESTs/mRNAs’. On the basis of these data, we inferred gene structure for this novel gene, with six exons marked as ‘1∼6’ in the track ‘<i>FLJ33706</i> Gene Structure’. The exons partially derived from re-sequenced data were highlighted in green. An ORF with two short coding exons located at exon 3 and exon 4 was identified to encode a 194-amino-acid-long peptide (track ‘Open Reading Frame (ORF)’). Newly inserted transposable elements, especially <i>Alu</i> sequences, contributed substantially to the formation of the first coding exon and six standard splicing junctions on the branch leading to human and chimpanzee, marked as ‘a∼f’ in the track ‘<i>FLJ33706</i> Gene Structure’. All repeat elements in this region were shown in track ‘RepeatMasker’, extracted from UCSC Genome Browser. Coding exons in tracks ‘Spliced Human EST’, ‘Human mRNA’ and ‘<i>FLJ33706</i> Gene Structure’ were represented by higher vertical bars, while UTR regions and intronic regions were represented by lower vertical bars. Size scales were added in the figure to give benchmarks for gene sizes. Tracks with different size scales were separated by horizon lines.</p>", "links"=>[], "tags"=>["human-specific", "protein-coding"], "article_id"=>526814, "categories"=>["Evolutionary Biology"], "users"=>["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"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1000734.g001", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Gene_structure_of_FLJ33706_a_human_specific_de_novo_protein_coding_gene_/526814", "title"=>"Gene structure of <i>FLJ33706</i>, a human-specific <i>de novo</i> protein-coding gene.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-03-26 01:53:34"}
  • {"files"=>["https://ndownloader.figshare.com/files/425771", "https://ndownloader.figshare.com/files/425776", "https://ndownloader.figshare.com/files/425784", "https://ndownloader.figshare.com/files/425801", "https://ndownloader.figshare.com/files/425812", "https://ndownloader.figshare.com/files/425823", "https://ndownloader.figshare.com/files/425838"], "description"=>"<div><p>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 <em>de novo</em> protein-coding gene, <em>FLJ33706</em> (alternative gene symbol <em>C20orf203</em>). Cross-species analysis revealed interesting evolutionary paths of how this gene had originated from noncoding DNA sequences: insertion of repeat elements especially <em>Alu</em> 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 <em>FLJ33706</em>'s mRNA and protein expression in the brain. Real-Time PCR in multiple tissues demonstrated that <em>FLJ33706</em> was most abundantly expressed in brain. Human polymorphism data suggested that <em>FLJ33706</em> 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. <em>FLJ33706</em> provided the strongest evidence so far that human-specific <em>de novo</em> genes can have protein-coding potential and differential protein expression, and be involved in human brain functions.</p></div>", "links"=>[], "tags"=>["human-specific", "protein-coding", "functions"], "article_id"=>144061, "categories"=>["Evolutionary Biology"], "users"=>["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"], "doi"=>["https://dx.doi.org/10.1371/journal.pcbi.1000734.s001", "https://dx.doi.org/10.1371/journal.pcbi.1000734.s002", "https://dx.doi.org/10.1371/journal.pcbi.1000734.s003", "https://dx.doi.org/10.1371/journal.pcbi.1000734.s004", "https://dx.doi.org/10.1371/journal.pcbi.1000734.s005", "https://dx.doi.org/10.1371/journal.pcbi.1000734.s006", "https://dx.doi.org/10.1371/journal.pcbi.1000734.s007"], "stats"=>{"downloads"=>14, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/A_Human_Specific_De_Novo_Protein_Coding_Gene_Associated_with_Human_Brain_Functions/144061", "title"=>"A Human-Specific <em>De Novo</em> Protein-Coding Gene Associated with Human Brain Functions", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2010-03-26 01:07:41"}
  • {"files"=>["https://ndownloader.figshare.com/files/856610"], "description"=>"<p>For each position in human <i>FLJ33706</i> ORF, the corresponding orthologous genomic sequences in chimpanzee, gorilla, orangutan and rhesus monkey were aligned to human reference to identify the types of variations. Only amino acid sites with at least one variation among “Human-Human” (SNP), “Human-Chimpanzee”, “Human-Gorilla”, “Human-Orangutan” or “Human-Rhesus” were shown. Identical sites were shown as black dots while divergent sites were shown in red (non-synonymous mutations), green (synonymous mutations) and blue (SNP). Two human-specific mutations that escaped stop codons were highlighted by black frames. Amino acids with non-synonymous variations were highlighted in red while synonymous variations in blue. All sequencing data in this study were traced and manually checked to ensure reliability.</p>", "links"=>[], "tags"=>["orf", "orthologous", "genomic", "sequences"], "article_id"=>527054, "categories"=>["Evolutionary Biology"], "users"=>["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"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1000734.g003", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Alignment_of_human_FLJ33706_ORF_with_orthologous_genomic_sequences_in_four_other_primates_/527054", "title"=>"Alignment of human <i>FLJ33706</i> ORF with orthologous genomic sequences in four other primates.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-03-26 01:57:34"}
  • {"files"=>["https://ndownloader.figshare.com/files/856928"], "description"=>"<p>Results from confocal immunofluorescence imaging to visualize FLJ33706 protein (red) in normal human cortex were shown. Neurons were marked with beta-tubulin-III (green). The nucleus was also stained with DAPI (blue). The optimal dilution of FLJ33706 antibody was optimised based on the detection of cytoplasmic signal in brain cells. The three rows showed results from three independent experiments.</p>", "links"=>[], "tags"=>["studies", "flj33706"], "article_id"=>527371, "categories"=>["Evolutionary Biology"], "users"=>["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"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1000734.g006", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Immunohistochemistry_studies_of_FLJ33706_protein_in_human_brain_/527371", "title"=>"Immunohistochemistry studies of FLJ33706 protein in human brain.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-03-26 02:02:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/856489"], "description"=>"<p>(<b>Top</b>) The syntenic alignments of five flanking splicing junctions of <i>FLJ33706</i> among 13 species were shown, in which intron regions were highlighted in blue boxes and splicing sites were highlighted in red. Lineage-specific insertions, unalignable bases in the gap region and uncertain regions were were marked as ‘-’, ‘ = ’ and ‘N’, respectively. (<b>Bottom</b>) The splicing sites from 8 species were shown in the context of the phylogeny. Red ‘Y’ represents presence of the splicing signal and blue ‘N’ represents absence. Exons and introns are not drawn to scale.</p>", "links"=>[], "tags"=>["alignments", "flanking", "splicing", "junctions"], "article_id"=>526934, "categories"=>["Evolutionary Biology"], "users"=>["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"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1000734.g002", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Syntenic_alignments_of_five_flanking_splicing_junctions_of_FLJ33706_/526934", "title"=>"Syntenic alignments of five flanking splicing junctions of <i>FLJ33706</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-03-26 01:55:34"}
  • {"files"=>["https://ndownloader.figshare.com/files/857038"], "description"=>"<p>Population genetics analyses of 90 individuals were performed and population genetics statistics of FLJ33706 were shown. CDS: coding sequences.</p>", "links"=>[], "tags"=>["genetics"], "article_id"=>527487, "categories"=>["Evolutionary Biology"], "users"=>["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"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1000734.t001", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_population_genetics_statistics_of_FLJ33706_/527487", "title"=>"population genetics statistics of <i>FLJ33706</i>.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2010-03-26 02:04:47"}
  • {"files"=>["https://ndownloader.figshare.com/files/856709"], "description"=>"<p><i>FLJ33706</i> mRNA levels were measured in eight peripheral tissues and eight brain regions using TaqMan-based Real-Time PCR system. Relative quantity was calculated using expression means of human leukocyte as references (Fold = 1.0). <i>FLJ33706</i> had relatively higher expression levels in brain regions (highlighted in red) than in peripheral tissues (shown in white). The expression levels of human BDNF1 and BDNF4 (shown in blue bars) in cortex (BDNF1_CTX, BDNF4_CTX) were also compared with those of <i>FLJ33706</i> using also leukocyte <i>FLJ3370</i>6 expression as a reference.</p>", "links"=>[], "tags"=>["mrna", "peripheral", "tissues"], "article_id"=>527154, "categories"=>["Evolutionary Biology"], "users"=>["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"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1000734.g004", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_FLJ33706_mRNA_expression_in_peripheral_tissues_and_brain_regions_/527154", "title"=>"<i>FLJ33706</i> mRNA expression in peripheral tissues and brain regions.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-03-26 01:59:14"}
  • {"files"=>["https://ndownloader.figshare.com/files/856816"], "description"=>"<p>(<b>A</b>) A specific band with molecular mass of about 22 kDa in SDS-PAGE, which was consistent with the predicted molecular weight of <i>FLJ33706</i> putative proteins, was detected in the Western-blot assay. The band could not be detected in pre-immune control and peptide competition control. Pre: pre-immune reaction assay; Ab: <i>FLJ33706</i> antibody assay; Pep: peptide competition assay. (<b>B</b>) <i>E. coli</i> samples before and after the transformation of FLJ33706 recombination plasmids were assayed by Western blot using (a) His-tag specific antibody and (b) anti-FLJ33706. FLJ33706 expression in human cortex was shown in (c) as the control. Before: <i>E. coli</i> samples before the plasmid transformation; After: <i>E. coli</i> samples after the plasmid transformation. (<b>C</b>) The specific band can be detected in all human brain regions, but not in mouse brain regions used as controls. H-CTX, M-CTX: human/mouse cortex; H-MID, M-MID: human/mouse midbrain; H-CER, M-CER: human/mouse cerebellum; (<b>D</b>) FLJ33706 expression can be detected in different human individuals. 384, 994, 275, 995, 705, 710, 1277: individual IDs. 22KD: theoretical molecular weight of FLJ33706 protein; 42KD: molecular weight of beta-actin protein as endogenous control. In A and C, antibodies for FLJ33706 and endogenous control were mixed in Western assays.</p>", "links"=>[], "tags"=>["assays", "levels"], "article_id"=>527263, "categories"=>["Evolutionary Biology"], "users"=>["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"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1000734.g005", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Western_blot_assays_to_determine_the_protein_expression_levels_of_FLJ33706_/527263", "title"=>"Western-blot assays to determine the protein expression levels of <i>FLJ33706</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-03-26 02:01:03"}

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