Identifying Signatures of Natural Selection in Tibetan and Andean Populations Using Dense Genome Scan Data
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{"title"=>"Identifying signatures of natural selection in Tibetan and Andean populations using dense genome scan data", "type"=>"journal", "authors"=>[{"first_name"=>"Abigail", "last_name"=>"Bigham", "scopus_author_id"=>"16644770400"}, {"first_name"=>"Marc", "last_name"=>"Bauchet", "scopus_author_id"=>"16244202800"}, {"first_name"=>"Dalila", "last_name"=>"Pinto", "scopus_author_id"=>"7005542371"}, {"first_name"=>"Xianyun", "last_name"=>"Mao", "scopus_author_id"=>"10046377700"}, {"first_name"=>"Joshua M.", "last_name"=>"Akey", "scopus_author_id"=>"6601938072"}, {"first_name"=>"Rui", "last_name"=>"Mei", "scopus_author_id"=>"7005238249"}, {"first_name"=>"Stephen W.", "last_name"=>"Scherer", "scopus_author_id"=>"35374654500"}, {"first_name"=>"Colleen G.", "last_name"=>"Julian", "scopus_author_id"=>"20734660400"}, {"first_name"=>"Megan J.", "last_name"=>"Wilson", "scopus_author_id"=>"56605560000"}, {"first_name"=>"David López", "last_name"=>"Herráez", "scopus_author_id"=>"25821997200"}, {"first_name"=>"Tom", "last_name"=>"Brutsaert", "scopus_author_id"=>"6701567852"}, {"first_name"=>"Esteban J.", "last_name"=>"Parra", "scopus_author_id"=>"7007088910"}, {"first_name"=>"Lorna G.", "last_name"=>"Moore", "scopus_author_id"=>"7401847284"}, {"first_name"=>"Mark D.", "last_name"=>"Shriver", "scopus_author_id"=>"24390641500"}], "year"=>2010, "source"=>"PLoS Genetics", "identifiers"=>{"scopus"=>"2-s2.0-78049419228", "sgr"=>"78049419228", "issn"=>"15537390", "isbn"=>"1553-7404 (Electronic)\\r1553-7390 (Linking)", "pmid"=>"20838600", "doi"=>"10.1371/journal.pgen.1001116", "pui"=>"359882498"}, "id"=>"c82ca925-427d-3441-80db-b412f1102214", "abstract"=>"High-altitude hypoxia (reduced inspired oxygen tension due to decreased barometric pressure) exerts severe physiological stress on the human body. Two high-altitude regions where humans have lived for millennia are the Andean Altiplano and the Tibetan Plateau. Populations living in these regions exhibit unique circulatory, respiratory, and hematological adaptations to life at high altitude. Although these responses have been well characterized physiologically, their underlying genetic basis remains unknown. We performed a genome scan to identify genes showing evidence of adaptation to hypoxia. We looked across each chromosome to identify genomic regions with previously unknown function with respect to altitude phenotypes. In addition, groups of genes functioning in oxygen metabolism and sensing were examined to test the hypothesis that particular pathways have been involved in genetic adaptation to altitude. Applying four population genetic statistics commonly used for detecting signatures of natural selection, we identified selection-nominated candidate genes and gene regions in these two populations (Andeans and Tibetans) separately. The Tibetan and Andean patterns of genetic adaptation are largely distinct from one another, with both populations showing evidence of positive natural selection in different genes or gene regions. Interestingly, one gene previously known to be important in cellular oxygen sensing, EGLN1 (also known as PHD2), shows evidence of positive selection in both Tibetans and Andeans. However, the pattern of variation for this gene differs between the two populations. Our results indicate that several key HIF-regulatory and targeted genes are responsible for adaptation to high altitude in Andeans and Tibetans, and several different chromosomal regions are implicated in the putative response to selection. These data suggest a genetic role in high-altitude adaption and provide a basis for future genotype/phenotype association studies necessary to confirm the role of selection-nominated candidate genes and gene regions in adaptation to altitude.", "link"=>"http://www.mendeley.com/research/identifying-signatures-natural-selection-tibetan-andean-populations-using-dense-genome-scan-data", "reader_count"=>280, "reader_count_by_academic_status"=>{"Unspecified"=>6, "Professor > Associate Professor"=>17, "Librarian"=>1, "Researcher"=>72, "Student > Doctoral Student"=>12, "Student > Ph. D. Student"=>82, "Student > Postgraduate"=>10, "Student > Master"=>32, "Other"=>5, "Student > Bachelor"=>22, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>2, "Professor"=>18}, "reader_count_by_user_role"=>{"Unspecified"=>6, "Professor > Associate Professor"=>17, "Librarian"=>1, "Researcher"=>72, "Student > Doctoral Student"=>12, "Student > Ph. D. 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  • {"files"=>["https://ndownloader.figshare.com/files/830961"], "description"=>"<p>The distribution of allele frequencies is shown for the two <i>EGLN1</i> SNPs, rs1769792 and rs12030600, exhibiting the highest ranked LSBL values in Andeans (A) and Tibetans (B), respectively. The derived G allele is shown red and the ancestral A allele is shown in black for rs1769792. The derived A allele is shown in red and the ancestral G allele is shown in black for rs12030600. LSBL, ln<i>RH</i>, and standardized difference of <i>D</i> are plotted for <i>EGLN1</i> including 500 kb upstream and downstream from the gene in (C) Andeans and (D) Tibetans. Significant SNPs or sliding windows are shown in red (P<sub>E</sub><0.05) whereas non-significant SNPs or SNP windows are depicted in blue. The genes found in the plotted region are shown below the plots. <i>EGLN1</i> is indicated in grey. The most frequent haplotype in the 100 kb region surrounding <i>EGLN1</i> is depicted for Andeans and Tibetans (E). Ancestral alleles are depicted in black and derived alleles are depicted red. The ancestral/derived state for a single site is unknown and is depicted as an unfilled box. The population frequency is listed to the right of each haplotype. The arrows indicate the location of the SNPs displaying the most extreme LSBL values plotted in 4A and 4B.</p>", "links"=>[], "tags"=>["evolutionary biology/human evolution", "genetics and genomics/population genetics"], "article_id"=>501313, "categories"=>["Evolutionary Biology", "Genetics"], "users"=>["Abigail Bigham", "Marc Bauchet", "Dalila Pinto", "Xianyun Mao", "Joshua M. Akey", "Rui Mei", "Stephen W. Scherer", "Colleen G. Julian", "Megan J. Wilson", "David López Herráez", "Tom Brutsaert", "Esteban J. Parra", "Lorna G. Moore", "Mark D. Shriver"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1001116.g004", "stats"=>{"downloads"=>5, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Genetic_variation_at_EGLN1_/501313", "title"=>"Genetic variation at <i>EGLN1</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-09-09 00:21:53"}
  • {"files"=>["https://ndownloader.figshare.com/files/831085"], "description"=>"<p>LSBL plotted for (A) 50 kb and (B) 500 kb surrounding <i>HBE1</i>. LSBL is shown on the X-axis and genomic position along chromosome 12 is shown on the Y-axis, with the axis labels located on the upper portion of the plots.</p>", "links"=>[], "tags"=>["evolutionary biology/human evolution", "genetics and genomics/population genetics"], "article_id"=>501442, "categories"=>["Evolutionary Biology", "Genetics"], "users"=>["Abigail Bigham", "Marc Bauchet", "Dalila Pinto", "Xianyun Mao", "Joshua M. Akey", "Rui Mei", "Stephen W. Scherer", "Colleen G. Julian", "Megan J. Wilson", "David López Herráez", "Tom Brutsaert", "Esteban J. Parra", "Lorna G. Moore", "Mark D. Shriver"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1001116.g005", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Genetic_variation_at_HBE1_/501442", "title"=>"Genetic variation at <i>HBE1</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-09-09 00:24:02"}
  • {"files"=>["https://ndownloader.figshare.com/files/830763"], "description"=>"<p>(A) Indigenous American individual genetic structure using PCA with a set of 221,046 SNPs selected to remove the influence of European admixture (see <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1001116#s4\" target=\"_blank\">Materials and Methods</a> and <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1001116#pgen.1001116.s001\" target=\"_blank\">Figure S1</a>) Europeans have been removed to simplify the representation; (B) East Asian individual genetic structure using PCA with the full set of 439,046 SNPs; (C) <i>Frappe</i> map file showing Indigenous American and (D) East Asian population structure. Population abbreviations are as in Figure 2A and Figure 2B, respectively. Additional European and African populations are included in the <i>frappe</i> bar chart in Figure 2C, and include Yoruban (YOR), Bantu (BAN), Berber (BER), French (FRE), and Tuscan (TUS). Each individual is represented by a vertical line that is divided into colored segments representing the genomic contribution from a particular <i>K</i> ancestral cluster.</p>", "links"=>[], "tags"=>["ancestry"], "article_id"=>501123, "categories"=>["Evolutionary Biology", "Genetics"], "users"=>["Abigail Bigham", "Marc Bauchet", "Dalila Pinto", "Xianyun Mao", "Joshua M. Akey", "Rui Mei", "Stephen W. Scherer", "Colleen G. Julian", "Megan J. Wilson", "David López Herráez", "Tom Brutsaert", "Esteban J. Parra", "Lorna G. Moore", "Mark D. Shriver"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1001116.g002", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Individual_ancestry_estimates_/501123", "title"=>"Individual ancestry estimates.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-09-09 00:18:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/831150"], "description"=>"<p>Autosomes and the X chromosome are listed separately.</p>", "links"=>[], "tags"=>["snps", "snp", "windows", "andeans", "tibetans"], "article_id"=>501505, "categories"=>["Evolutionary Biology", "Genetics"], "users"=>["Abigail Bigham", "Marc Bauchet", "Dalila Pinto", "Xianyun Mao", "Joshua M. Akey", "Rui Mei", "Stephen W. Scherer", "Colleen G. Julian", "Megan J. Wilson", "David López Herráez", "Tom Brutsaert", "Esteban J. Parra", "Lorna G. Moore", "Mark D. Shriver"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1001116.t001", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Significant_SNPs_or_SNP_windows_in_Andeans_and_Tibetans_for_P_E_8804_0_05_and_P_E_8804_0_01_/501505", "title"=>"Significant SNPs or SNP windows in Andeans and Tibetans for P<sub>E</sub>≤0.05 and P<sub>E</sub>≤0.01.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2010-09-09 00:25:05"}
  • {"files"=>["https://ndownloader.figshare.com/files/830652"], "description"=>"<p>Geographic locations where humans have adapted to life at high-altitude are indicated in grey and include the Andean Altiplano of South America, the Tibetan Plateau of Central Asia, and the Semien Plateau of Ethiopia. Only populations from the Andean Altiplano and the Tibetan Plateau were considered here. Inset: Map locations of the four Native American population samples including Peruvian Quechua, Bolivian Aymara, Nahua, Mixtec, and Tlapanec speakers from Guerrero, Mexico, and Maya from the Yucatan Peninsula, Mexico.</p>", "links"=>[], "tags"=>["geography", "adaptation"], "article_id"=>501006, "categories"=>["Evolutionary Biology", "Genetics"], "users"=>["Abigail Bigham", "Marc Bauchet", "Dalila Pinto", "Xianyun Mao", "Joshua M. Akey", "Rui Mei", "Stephen W. Scherer", "Colleen G. Julian", "Megan J. Wilson", "David López Herráez", "Tom Brutsaert", "Esteban J. Parra", "Lorna G. Moore", "Mark D. Shriver"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1001116.g001", "stats"=>{"downloads"=>1, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_geography_of_human_adaptation_to_high_altitude_/501006", "title"=>"The geography of human adaptation to high altitude.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-09-09 00:16:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/831260"], "description"=>"<p>Empirical distribution rank and P<sub>E</sub> value for each significant <i>EGLN1</i> SNP in both Andeans and Tibetans.</p>", "links"=>[], "tags"=>["snp", "andeans"], "article_id"=>501618, "categories"=>["Evolutionary Biology", "Genetics"], "users"=>["Abigail Bigham", "Marc Bauchet", "Dalila Pinto", "Xianyun Mao", "Joshua M. Akey", "Rui Mei", "Stephen W. Scherer", "Colleen G. Julian", "Megan J. Wilson", "David López Herráez", "Tom Brutsaert", "Esteban J. Parra", "Lorna G. Moore", "Mark D. Shriver"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1001116.t003", "stats"=>{"downloads"=>4, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Empirical_distribution_rank_and_P_E_value_for_each_significant_EGLN1_SNP_in_both_Andeans_and_Tibetans_/501618", "title"=>"Empirical distribution rank and P<sub>E</sub> value for each significant <i>EGLN1</i> SNP in both Andeans and Tibetans.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2010-09-09 00:26:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/830853"], "description"=>"<p>The most significant test statistics for the HIF pathway candidate genes are plotted against the null distribution generated by plotting the highest ranked (i.e. most significant) test statistic for each gene from the dataset for LSBL in (A) Andeans and (B) Tibetans, for ln<i>RH</i> in (C) Andeans and (D) Tibetans, and for the standardized difference of <i>D</i> for in (E) Andeans and (F) Tibetans. The solid line indicates the 5% empirical cut off and the dashed line indicates the 1% empirical cut off for each distribution. The maximum test statistic for each of the HIF pathway candidate genes that had one or more SNPs falling in the top 5% of the empirical distribution is plotted on the figure as a solid circle. Those SNPs that fall in the top 5% of the empirical distribution and that are significant under the null distribution shown here for each population are plotted as numbers. In Figure A, 1 = <i>EGLN1</i>, 2 = <i>NOS2A</i>, 3 = <i>TGFA</i>, 4 = <i>CXCR4</i>, and 5 = <i>PRKAA1</i>. For Figure B, 1 = <i>EPAS1</i>, 2 = <i>EPO</i>, 3 = <i>CASR</i>, 4 = <i>EDN1</i>, and 5 = <i>EGLN1</i>. For Figure C, 1 = <i>ELF2</i>, 2 = <i>IL1A/IL1B</i>, 3 = <i>TNC</i>, 4 = <i>FRAP1</i>, 5 = <i>POLR2A</i>. For Figure D, 1 = <i>PIK3CB</i>, 2 = <i>COPS5</i>, <i>3 = EGLN1</i>, <i>4 = VEGFC</i>, <i>5 = IL1B</i>, <i>6 = EPAS1</i>, <i>7 = RBX1</i>, <i>8 = IL1A</i>. In Figure E, 1 = <i>PRKAA1</i>, 2 = <i>NOS2A</i>, 3 = <i>EDNRB</i>. For Figure F, 1 = <i>EPAS1</i>, 2 = <i>ARNT</i>, 3 = <i>ADRA1B</i>.</p>", "links"=>[], "tags"=>["pathway", "genes", "directional", "andeans"], "article_id"=>501203, "categories"=>["Evolutionary Biology", "Genetics"], "users"=>["Abigail Bigham", "Marc Bauchet", "Dalila Pinto", "Xianyun Mao", "Joshua M. Akey", "Rui Mei", "Stephen W. Scherer", "Colleen G. Julian", "Megan J. Wilson", "David López Herráez", "Tom Brutsaert", "Esteban J. Parra", "Lorna G. Moore", "Mark D. Shriver"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1001116.g003", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_HIF_pathway_candidate_genes_showing_evidence_of_positive_directional_selection_in_Andeans_and_Tibetans_/501203", "title"=>"HIF pathway candidate genes showing evidence of positive directional selection in Andeans and Tibetans.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-09-09 00:20:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/831206"], "description"=>"<p>Total LSBL SNPs, ln<i>RH</i> windows, or the standardized difference of <i>D</i> windows analyzed for the HIF pathway, RAS, and globin family.</p>", "links"=>[], "tags"=>["lsbl", "standardized", "windows", "hif", "globin"], "article_id"=>501557, "categories"=>["Evolutionary Biology", "Genetics"], "users"=>["Abigail Bigham", "Marc Bauchet", "Dalila Pinto", "Xianyun Mao", "Joshua M. Akey", "Rui Mei", "Stephen W. Scherer", "Colleen G. Julian", "Megan J. Wilson", "David López Herráez", "Tom Brutsaert", "Esteban J. Parra", "Lorna G. Moore", "Mark D. Shriver"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1001116.t002", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Total_LSBL_SNPs_ln_RH_windows_or_the_standardized_difference_of_D_windows_analyzed_for_the_HIF_pathway_RAS_and_globin_family_/501557", "title"=>"Total LSBL SNPs, ln<i>RH</i> windows, or the standardized difference of <i>D</i> windows analyzed for the HIF pathway, RAS, and globin family.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2010-09-09 00:25:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/413887", "https://ndownloader.figshare.com/files/413914", "https://ndownloader.figshare.com/files/413941", "https://ndownloader.figshare.com/files/413970", "https://ndownloader.figshare.com/files/414010", "https://ndownloader.figshare.com/files/414054", "https://ndownloader.figshare.com/files/414089", "https://ndownloader.figshare.com/files/414123", "https://ndownloader.figshare.com/files/414157", "https://ndownloader.figshare.com/files/414201", "https://ndownloader.figshare.com/files/414226"], "description"=>"<div><p>High-altitude hypoxia (reduced inspired oxygen tension due to decreased barometric pressure) exerts severe physiological stress on the human body. Two high-altitude regions where humans have lived for millennia are the Andean Altiplano and the Tibetan Plateau. Populations living in these regions exhibit unique circulatory, respiratory, and hematological adaptations to life at high altitude. Although these responses have been well characterized physiologically, their underlying genetic basis remains unknown. We performed a genome scan to identify genes showing evidence of adaptation to hypoxia. We looked across each chromosome to identify genomic regions with previously unknown function with respect to altitude phenotypes. In addition, groups of genes functioning in oxygen metabolism and sensing were examined to test the hypothesis that particular pathways have been involved in genetic adaptation to altitude. Applying four population genetic statistics commonly used for detecting signatures of natural selection, we identified selection-nominated candidate genes and gene regions in these two populations (Andeans and Tibetans) separately. The Tibetan and Andean patterns of genetic adaptation are largely distinct from one another, with both populations showing evidence of positive natural selection in different genes or gene regions. Interestingly, one gene previously known to be important in cellular oxygen sensing, <em>EGLN1</em> (also known as <em>PHD2</em>), shows evidence of positive selection in both Tibetans and Andeans. However, the pattern of variation for this gene differs between the two populations. Our results indicate that several key HIF-regulatory and targeted genes are responsible for adaptation to high altitude in Andeans and Tibetans, and several different chromosomal regions are implicated in the putative response to selection. These data suggest a genetic role in high-altitude adaption and provide a basis for future genotype/phenotype association studies necessary to confirm the role of selection-nominated candidate genes and gene regions in adaptation to altitude.</p></div>", "links"=>[], "tags"=>["identifying", "signatures", "tibetan", "andean", "populations", "genome"], "article_id"=>141753, "categories"=>["Evolutionary Biology", "Genetics"], "users"=>["Abigail Bigham", "Marc Bauchet", "Dalila Pinto", "Xianyun Mao", "Joshua M. Akey", "Rui Mei", "Stephen W. Scherer", "Colleen G. Julian", "Megan J. Wilson", "David López Herráez", "Tom Brutsaert", "Esteban J. Parra", "Lorna G. Moore", "Mark D. Shriver"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1001116.s001", "https://dx.doi.org/10.1371/journal.pgen.1001116.s002", "https://dx.doi.org/10.1371/journal.pgen.1001116.s003", "https://dx.doi.org/10.1371/journal.pgen.1001116.s004", "https://dx.doi.org/10.1371/journal.pgen.1001116.s005", "https://dx.doi.org/10.1371/journal.pgen.1001116.s006", "https://dx.doi.org/10.1371/journal.pgen.1001116.s007", "https://dx.doi.org/10.1371/journal.pgen.1001116.s008", "https://dx.doi.org/10.1371/journal.pgen.1001116.s009", "https://dx.doi.org/10.1371/journal.pgen.1001116.s010", "https://dx.doi.org/10.1371/journal.pgen.1001116.s011"], "stats"=>{"downloads"=>59, "page_views"=>18, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Identifying_Signatures_of_Natural_Selection_in_Tibetan_and_Andean_Populations_Using_Dense_Genome_Scan_Data/141753", "title"=>"Identifying Signatures of Natural Selection in Tibetan and Andean Populations Using Dense Genome Scan Data", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2010-09-09 00:29:13"}

PMC Usage Stats | Further Information

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  • {"unique-ip"=>"43", "full-text"=>"45", "pdf"=>"10", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"8", "cited-by"=>"1", "year"=>"2018", "month"=>"11"}
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Relative Metric

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