Gene Losses during Human Origins
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{"title"=>"Gene losses during human origins", "type"=>"journal", "authors"=>[{"first_name"=>"Xiaoxia", "last_name"=>"Wang", "scopus_author_id"=>"8945695800"}, {"first_name"=>"Wendy E.", "last_name"=>"Grus", "scopus_author_id"=>"8566654400"}, {"first_name"=>"Jianzhi", "last_name"=>"Zhang", "scopus_author_id"=>"56752433600"}], "year"=>2006, "source"=>"PLoS Biology", "identifiers"=>{"scopus"=>"2-s2.0-33644980516", "sgr"=>"33644980516", "issn"=>"15457885", "isbn"=>"1545-7885 (Electronic) 1544-9173 (Linking)", "pmid"=>"16464126", "doi"=>"10.1371/journal.pbio.0040052", "pui"=>"43396247"}, "id"=>"27b58f31-1789-362c-8c13-b276124f1a2c", "abstract"=>"Pseudogenization is a widespread phenomenon in genome evolution, and it has been proposed to serve as an engine of evolutionary change, especially during human origins (the \"less-is-more\" hypothesis). However, there has been no comprehensive analysis of human-specific pseudogenes. Furthermore, it is unclear whether pseudogenization itself can be selectively favored and thus play an active role in human evolution. Here we conduct a comparative genomic analysis and a literature survey to identify 80 nonprocessed pseudogenes that were inactivated in the human lineage after its separation from the chimpanzee lineage. Many functions are involved among these genes, with chemoreception and immune response being outstandingly overrepresented, suggesting potential species-specific features in these aspects of human physiology. To explore the possibility of adaptive pseudogenization, we focus on CASPASE12, a cysteinyl aspartate proteinase participating in inflammatory and innate immune response to endotoxins. We provide population genetic evidence that the nearly complete fixation of a null allele at CASPASE12 has been driven by positive selection, probably because the null allele confers protection from severe sepsis. We estimate that the selective advantage of the null allele is about 0.9% and the pseudogenization started shortly before the out-of-Africa migration of modern humans. Interestingly, two other genes related to sepsis were also pseudogenized in humans, possibly by selection. These adaptive gene losses might have occurred because of changes in our environment or genetic background that altered the threat from or response to sepsis. The identification and analysis of human-specific pseudogenes open the door for understanding the roles of gene losses in human origins, and the demonstration that gene loss itself can be adaptive supports and extends the \"less-is-more\" hypothesis.", "link"=>"http://www.mendeley.com/research/gene-losses-during-human-origins", "reader_count"=>204, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>23, "Researcher"=>49, "Student > Doctoral Student"=>5, "Student > Ph. D. Student"=>39, "Student > Postgraduate"=>6, "Student > Master"=>14, "Other"=>10, "Student > Bachelor"=>28, "Lecturer"=>2, "Lecturer > Senior Lecturer"=>4, "Professor"=>22}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>23, "Researcher"=>49, "Student > Doctoral Student"=>5, "Student > Ph. D. Student"=>39, "Student > Postgraduate"=>6, "Student > Master"=>14, "Other"=>10, "Student > Bachelor"=>28, "Lecturer"=>2, "Lecturer > Senior Lecturer"=>4, "Professor"=>22}, "reader_count_by_subject_area"=>{"Unspecified"=>4, "Agricultural and Biological Sciences"=>136, "Arts and Humanities"=>2, "Philosophy"=>1, "Computer Science"=>4, "Earth and Planetary Sciences"=>1, "Environmental Science"=>3, "Biochemistry, Genetics and Molecular Biology"=>25, "Mathematics"=>2, "Medicine and Dentistry"=>5, "Neuroscience"=>2, "Physics and Astronomy"=>2, "Psychology"=>6, "Social Sciences"=>9, "Immunology and Microbiology"=>2}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>5}, "Social Sciences"=>{"Social Sciences"=>9}, "Physics and Astronomy"=>{"Physics and Astronomy"=>2}, "Psychology"=>{"Psychology"=>6}, "Mathematics"=>{"Mathematics"=>2}, "Unspecified"=>{"Unspecified"=>4}, "Environmental Science"=>{"Environmental Science"=>3}, "Arts and Humanities"=>{"Arts and Humanities"=>2}, "Neuroscience"=>{"Neuroscience"=>2}, "Earth and Planetary Sciences"=>{"Earth and Planetary Sciences"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>136}, "Computer Science"=>{"Computer Science"=>4}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>25}, "Philosophy"=>{"Philosophy"=>1}}, "reader_count_by_country"=>{"Argentina"=>2, "Romania"=>1, "United States"=>15, "United Kingdom"=>1, "Switzerland"=>1, "Spain"=>3, "Russia"=>1, "Canada"=>1, "Sweden"=>1, "Netherlands"=>1, "Norway"=>1, "Denmark"=>1, "Brazil"=>2, "South Africa"=>1, "Mexico"=>2, "Chile"=>1, "Germany"=>3}, "group_count"=>9}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/474472", "https://ndownloader.figshare.com/files/474517", "https://ndownloader.figshare.com/files/474584", "https://ndownloader.figshare.com/files/474681", "https://ndownloader.figshare.com/files/474704", "https://ndownloader.figshare.com/files/474723", "https://ndownloader.figshare.com/files/474739"], "description"=>"<div><p>Pseudogenization is a widespread phenomenon in genome evolution, and it has been proposed to serve as an engine of evolutionary change, especially during human origins (the “less-is-more” hypothesis). However, there has been no comprehensive analysis of human-specific pseudogenes. Furthermore, it is unclear whether pseudogenization itself can be selectively favored and thus play an active role in human evolution. Here we conduct a comparative genomic analysis and a literature survey to identify 80 nonprocessed pseudogenes that were inactivated in the human lineage after its separation from the chimpanzee lineage. Many functions are involved among these genes, with chemoreception and immune response being outstandingly overrepresented, suggesting potential species-specific features in these aspects of human physiology. To explore the possibility of adaptive pseudogenization, we focus on CASPASE12, a cysteinyl aspartate proteinase participating in inflammatory and innate immune response to endotoxins. We provide population genetic evidence that the nearly complete fixation of a null allele at <em>CASPASE12</em> has been driven by positive selection, probably because the null allele confers protection from severe sepsis. We estimate that the selective advantage of the null allele is about 0.9% and the pseudogenization started shortly before the out-of-Africa migration of modern humans. Interestingly, two other genes related to sepsis were also pseudogenized in humans, possibly by selection. These adaptive gene losses might have occurred because of changes in our environment or genetic background that altered the threat from or response to sepsis. The identification and analysis of human-specific pseudogenes open the door for understanding the roles of gene losses in human origins, and the demonstration that gene loss itself can be adaptive supports and extends the “less-is-more” hypothesis.</p> </div>", "links"=>[], "tags"=>["losses", "origins"], "article_id"=>153519, "categories"=>["Biological Sciences", "Genetics", "Evolutionary Biology"], "users"=>["Xiaoxia Wang", "Wendy E Grus", "Jianzhi Zhang"], "doi"=>["https://dx.doi.org/10.1371/journal.pbio.0040052.sg001", "https://dx.doi.org/10.1371/journal.pbio.0040052.sg002", "https://dx.doi.org/10.1371/journal.pbio.0040052.sd001", "https://dx.doi.org/10.1371/journal.pbio.0040052.st001", "https://dx.doi.org/10.1371/journal.pbio.0040052.st002", "https://dx.doi.org/10.1371/journal.pbio.0040052.st003", "https://dx.doi.org/10.1371/journal.pbio.0040052.st004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Gene_Losses_during_Human_Origins/153519", "title"=>"Gene Losses during Human Origins", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2006-02-14 00:58:39"}
  • {"files"=>["https://ndownloader.figshare.com/files/959987"], "description"=>"<p>The number of pseudogenes left after each step is given in the boxes.</p>", "links"=>[], "tags"=>["67", "human-specific", "nonprocessed"], "article_id"=>630000, "categories"=>["Biological Sciences", "Genetics", "Evolutionary Biology"], "users"=>["Xiaoxia Wang", "Wendy E Grus", "Jianzhi Zhang"], "doi"=>["https://dx.doi.org/10.1371/journal.pbio.0040052.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Flow_Chart_for_Identifying_the_67_Human_Specific_Nonprocessed_Pseudogenes_/630000", "title"=>"Flow Chart for Identifying the 67 Human-Specific Nonprocessed Pseudogenes", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-22 08:46:54"}
  • {"files"=>["https://ndownloader.figshare.com/files/960100"], "description"=>"<div><p>Functional genes and pseudogenes are represented by open and closed circles, respectively. A, A1, A2, and B represent hypothetical gene names.</p>\n <p>(A) The human-specific pseudogene has a functional chimpanzee ortholog.</p>\n <p>(B) The chimpanzee functional gene is most closely related to another chimpanzee functional gene.</p>\n <p>(C) The human pseudogene is most closely related to a functional human gene.</p>\n <p>(D) The chimpanzee functional ortholog is most closely related to a human functional gene. We consider (A) and (B) as human-specific pseudogenes.</p></div>", "links"=>[], "tags"=>["scenarios", "human-specific", "pseudogenes"], "article_id"=>630113, "categories"=>["Biological Sciences", "Genetics", "Evolutionary Biology"], "users"=>["Xiaoxia Wang", "Wendy E Grus", "Jianzhi Zhang"], "doi"=>["https://dx.doi.org/10.1371/journal.pbio.0040052.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Evolutionary_Scenarios_for_Human_Specific_Pseudogenes_and_Non_8211_Human_Specific_Pseudogenes_/630113", "title"=>"Evolutionary Scenarios for Human-Specific Pseudogenes and Non–Human-Specific Pseudogenes", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-22 08:47:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/960158"], "description"=>"<p><i>CASPASE12</i> is shown in blue, with the exons depicted by solid blue bars on the chromosome. The premature stop codon generated by the C → T nonsense mutation is shown by an asterisk in exon 4. The nine noncoding regions sequenced are indicated below the chromosome. Exons, introns, the nine noncoding regions, and spaces between regions are drawn to scale as indicated. Red circles (connected by the red dotted line) show nucleotide diversity per site among African T alleles (π<sub>T</sub>) and the red boxes shows π<sub>T</sub> ± one standard error of π<sub>T</sub>. Green squares (connected by the green dotted line) show nucleotide diversity per site among African C alleles (π<sub>C</sub>) and the green boxes shows π<sub>C</sub> ± one standard error of π<sub>C</sub>. The broken green line shows the mean π<sub>C</sub> across the nine noncoding regions sequenced. Black triangles (connected by the black solid line) show the ratio between π<sub>T</sub> and π<sub>C</sub> for each region. π<sub>C</sub> is estimated from eight alleles. π<sub>T</sub> is estimated from 22 alleles for regions 4, 5, and 6 and from eight alleles for the other regions. When only eight alleles are used, π<sub>T</sub> is 0.00018 ± 0.00007, 0.00129 ± 0.00071, and 0.00145 ± 0.00057 for regions 4, 5, and 6, respectively. π<sub>T</sub> is significantly lower than π<sub>C</sub> in regions 4 and 5 (<a href=\"http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0040052#st002\" target=\"_blank\">Table S2</a>).</p>", "links"=>[], "tags"=>["dna", "noncoding", "regions", "linked"], "article_id"=>630172, "categories"=>["Biological Sciences", "Genetics", "Evolutionary Biology"], "users"=>["Xiaoxia Wang", "Wendy E Grus", "Jianzhi Zhang"], "doi"=>["https://dx.doi.org/10.1371/journal.pbio.0040052.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Intraspecific_DNA_Sequence_Variation_in_Noncoding_Regions_Linked_with_the_Human_CASP12_Gene_/630172", "title"=>"Intraspecific DNA Sequence Variation in Noncoding Regions Linked with the Human <i>CASP12</i> Gene", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-22 08:48:06"}

PMC Usage Stats | Further Information

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Relative Metric

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