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<!DOCTYPE html> <html > <head> <meta charset="utf-8"> <meta rel="search" type="application/opensearchdescription+xml" href="/open_search.xml" title="Academia.edu"> <meta content="width=device-width, initial-scale=1" name="viewport"> <meta name="google-site-verification" content="bKJMBZA7E43xhDOopFZkssMMkBRjvYERV-NaN4R6mrs"> <meta name="csrf-param" content="authenticity_token" /> <meta name="csrf-token" content="R8gAodrod3rks6xZN-gB2q1dJ_I7l2qg6WNoT6Re0ohz6bApSdZ6iIhPMSni0XE3QhMfzQ6qfVSmDQ8K0EYtNA" /> <meta name="citation_title" content="Differential DNA methylation of vocal and facial anatomy genes in modern humans" /> <meta name="citation_author" content="Ron Pinhasi" /> <meta name="citation_author" content="Olivia Cheronet" /> <meta name="citation_author" content="David Gokhman" /> <meta name="citation_author" content="Songül Alpaslan-Roodenberg" /> <meta name="citation_author" content="CARLES LALUEZA-FOX" /> <meta name="twitter:card" content="summary" /> <meta name="twitter:url" content="https://www.academia.edu/44278503/Differential_DNA_methylation_of_vocal_and_facial_anatomy_genes_in_modern_humans" /> <meta name="twitter:title" content="Differential DNA methylation of vocal and facial anatomy genes in modern humans" /> <meta name="twitter:description" content="Changes in potential regulatory elements are thought to be key drivers of phenotypic divergence. However, identifying changes to regulatory elements that underlie human-specific traits has proven very challenging. Here, we use 63 reconstructed and" /> <meta name="twitter:image" content="https://0.academia-photos.com/6077609/6501440/7352008/s200_ron.pinhasi.jpg" /> <meta property="fb:app_id" content="2369844204" /> <meta property="og:type" content="article" /> <meta property="og:url" content="https://www.academia.edu/44278503/Differential_DNA_methylation_of_vocal_and_facial_anatomy_genes_in_modern_humans" /> <meta property="og:title" content="Differential DNA methylation of vocal and facial anatomy genes in modern humans" /> <meta property="og:image" content="http://a.academia-assets.com/images/open-graph-icons/fb-paper.gif" /> <meta property="og:description" content="Changes in potential regulatory elements are thought to be key drivers of phenotypic divergence. However, identifying changes to regulatory elements that underlie human-specific traits has proven very challenging. Here, we use 63 reconstructed and" /> <meta property="article:author" content="https://univie.academia.edu/RonPinhasi" /> <meta property="article:author" content="https://huji.academia.edu/DavidGokhman" /> <meta property="article:author" content="https://univie.academia.edu/OliviaCheronet" /> <meta property="article:author" content="https://univie.academia.edu/Song%C3%BClAlpaslanRoodenberg" /> <meta property="article:author" content="https://upf.academia.edu/CARLESLALUEZAFOX" /> <meta name="description" content="Changes in potential regulatory elements are thought to be key drivers of phenotypic divergence. However, identifying changes to regulatory elements that underlie human-specific traits has proven very challenging. Here, we use 63 reconstructed and" /> <title>Differential DNA methylation of vocal and facial anatomy genes in modern humans</title> <link rel="canonical" href="https://www.academia.edu/44278503/Differential_DNA_methylation_of_vocal_and_facial_anatomy_genes_in_modern_humans" /> <script async src="https://www.googletagmanager.com/gtag/js?id=G-5VKX33P2DS"></script> <script> window.dataLayer = window.dataLayer || []; function gtag(){dataLayer.push(arguments);} gtag('js', new Date()); gtag('config', 'G-5VKX33P2DS', { cookie_domain: 'academia.edu', send_page_view: false, }); gtag('event', 'page_view', { 'controller': "single_work", 'action': "show", 'controller_action': 'single_work#show', 'logged_in': 'false', 'edge': 'unknown', // Send nil if there is no A/B test bucket, in case some records get logged // with missing data - that way we can distinguish between the two cases. // ab_test_bucket should be of the form <ab_test_name>:<bucket> 'ab_test_bucket': null, }) </script> <script> var $controller_name = 'single_work'; var $action_name = "show"; var $rails_env = 'production'; var $app_rev = '107520bac59918e2ceae62eaadd15bff3d1e7904'; var $domain = 'academia.edu'; var $app_host = "academia.edu"; var $asset_host = "academia-assets.com"; var $start_time = new Date().getTime(); var $recaptcha_key = "6LdxlRMTAAAAADnu_zyLhLg0YF9uACwz78shpjJB"; var $recaptcha_invisible_key = "6Lf3KHUUAAAAACggoMpmGJdQDtiyrjVlvGJ6BbAj"; var $disableClientRecordHit = false; </script> <script> window.require = { config: function() { return function() {} } } </script> <script> window.Aedu = window.Aedu || {}; window.Aedu.hit_data = null; window.Aedu.serverRenderTime = new Date(1740874879000); window.Aedu.timeDifference = new Date().getTime() - 1740874879000; </script> <script type="application/ld+json">{"@context":"https://schema.org","@type":"ScholarlyArticle","abstract":"Changes in potential regulatory elements are thought to be key drivers of phenotypic divergence. However, identifying changes to regulatory elements that underlie human-specific traits has proven very challenging. Here, we use 63 reconstructed and experimentally measured DNA methylation maps of ancient and present-day humans, as well as of six chimpanzees, to detect differentially methylated regions that likely emerged in modern humans after the split from Neanderthals and Denisovans. We show that genes associated with face and vocal tract anatomy went through particularly extensive methylation changes. Specifically, we identify widespread hypermethylation in a network of face-and voice-associated genes (SOX9, ACAN, COL2A1, NFIX and XYLT1). We propose that these repression patterns appeared after the split from Neanderthals and Denisovans, and that they might have played a key role in shaping the modern human face and vocal tract.","author":[{"@context":"https://schema.org","@type":"Person","name":"Ron Pinhasi","url":"https://univie.academia.edu/RonPinhasi","image":"https://0.academia-photos.com/6077609/6501440/7352008/s200_ron.pinhasi.jpg","sameAs":[]},{"@context":"https://schema.org","@type":"Person","name":"David Gokhman","url":"https://huji.academia.edu/DavidGokhman","image":"https://0.academia-photos.com/53176588/15230742/15905539/s200_david.gokhman.jpg","sameAs":[]},{"@context":"https://schema.org","@type":"Person","name":"Olivia Cheronet","url":"https://univie.academia.edu/OliviaCheronet","image":"https://0.academia-photos.com/2627065/144439672/133963348/s200_olivia.cheronet.png","sameAs":[]},{"@context":"https://schema.org","@type":"Person","name":"Songül Alpaslan-Roodenberg","url":"https://univie.academia.edu/Song%C3%BClAlpaslanRoodenberg","image":"https://0.academia-photos.com/907564/335660/164663941/s200_song_l.alpaslan-roodenberg.jpg","sameAs":[]},{"@context":"https://schema.org","@type":"Person","name":"CARLES LALUEZA-FOX","url":"https://upf.academia.edu/CARLESLALUEZAFOX","image":"https://0.academia-photos.com/36529252/11541473/12871786/s200_carles.lalueza-fox.jpg","sameAs":[]}],"contributor":[{"@context":"https://schema.org","@type":"Person","name":"David Gokhman","url":"https://huji.academia.edu/DavidGokhman","image":"https://0.academia-photos.com/53176588/15230742/15905539/s200_david.gokhman.jpg","sameAs":[]},{"@context":"https://schema.org","@type":"Person","name":"Olivia Cheronet","url":"https://univie.academia.edu/OliviaCheronet","image":"https://0.academia-photos.com/2627065/144439672/133963348/s200_olivia.cheronet.png","sameAs":[]},{"@context":"https://schema.org","@type":"Person","name":"Songül Alpaslan-Roodenberg","url":"https://univie.academia.edu/Song%C3%BClAlpaslanRoodenberg","image":"https://0.academia-photos.com/907564/335660/164663941/s200_song_l.alpaslan-roodenberg.jpg","sameAs":[]},{"@context":"https://schema.org","@type":"Person","name":"CARLES LALUEZA-FOX","url":"https://upf.academia.edu/CARLESLALUEZAFOX","image":"https://0.academia-photos.com/36529252/11541473/12871786/s200_carles.lalueza-fox.jpg","sameAs":[]}],"dateCreated":"2020-10-12","dateModified":"2020-10-25","headline":"Differential DNA methylation of vocal and facial anatomy genes in modern 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However, identifying changes to regulatory elements that underlie human-specific traits has proven very challenging. Here, we use 63 reconstructed and experimentally measured DNA methylation maps of ancient and present-day humans, as well as of six chimpanzees, to detect differentially methylated regions that likely emerged in modern humans after the split from Neanderthals and Denisovans. We show that genes associated with face and vocal tract anatomy went through particularly extensive methylation changes. Specifically, we identify widespread hypermethylation in a network of face-and voice-associated genes (SOX9, ACAN, COL2A1, NFIX and XYLT1). We propose that these repression patterns appeared after the split from Neanderthals and Denisovans, and that they might have played a key role in shaping the modern human face and vocal tract."},"document_type":"paper","pre_hit_view_count_baseline":null,"quality":"low","language":"en","title":"Differential DNA methylation of vocal and facial anatomy genes in modern humans","broadcastable":true,"draft":null,"has_indexable_attachment":true,"indexable":true,"seo_quality":null}}["work"]; window.loswp.workCoauthors = [6077609,2627065,53176588,907564,36529252]; window.loswp.locale = "en"; window.loswp.countryCode = "SG"; window.loswp.cwvAbTestBucket = ""; window.loswp.designVariant = "ds_vanilla"; window.loswp.fullPageMobileSutdModalVariant = "control"; window.loswp.useOptimizedScribd4genScript = false; window.loginModal = {}; window.loginModal.appleClientId = 'edu.academia.applesignon'; window.userInChina = "false";</script><script defer="" src="https://accounts.google.com/gsi/client"></script><div class="ds-loswp-container"><div class="ds-work-card--grid-container"><div class="ds-work-card--container js-loswp-work-card"><div class="ds-work-card--cover"><div class="ds-work-cover--wrapper"><div class="ds-work-cover--container"><button class="ds-work-cover--clickable js-swp-download-button" data-signup-modal="{"location":"swp-splash-paper-cover","attachmentId":64657110,"attachmentType":"pdf"}"><img alt="First page of “Differential DNA methylation of vocal and facial anatomy genes in modern humans”" class="ds-work-cover--cover-thumbnail" src="https://0.academia-photos.com/attachment_thumbnails/64657110/mini_magick20201012-10490-1kg506x.png?1602497758" /><img alt="PDF Icon" class="ds-work-cover--file-icon" src="//a.academia-assets.com/images/single_work_splash/adobe_icon.svg" /><div class="ds-work-cover--hover-container"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">download</span><p>Download Free PDF</p></div><div class="ds-work-cover--ribbon-container">Download Free PDF</div><div class="ds-work-cover--ribbon-triangle"></div></button></div></div></div><div class="ds-work-card--work-information"><h1 class="ds-work-card--work-title">Differential DNA methylation of vocal and facial anatomy genes in modern humans</h1><div class="ds-work-card--work-authors ds-work-card--detail"><a class="ds-work-card--author js-wsj-grid-card-author ds2-5-body-md ds2-5-body-link" data-author-id="6077609" href="https://univie.academia.edu/RonPinhasi"><img alt="Profile image of Ron Pinhasi" class="ds-work-card--author-avatar" src="https://0.academia-photos.com/6077609/6501440/7352008/s65_ron.pinhasi.jpg" />Ron Pinhasi</a><a class="ds-work-card--author js-wsj-grid-card-author ds2-5-body-md ds2-5-body-link" data-author-id="2627065" href="https://univie.academia.edu/OliviaCheronet"><img alt="Profile image of Olivia Cheronet" class="ds-work-card--author-avatar" src="https://0.academia-photos.com/2627065/144439672/133963348/s65_olivia.cheronet.png" />Olivia Cheronet</a><a class="ds-work-card--author js-wsj-grid-card-author ds2-5-body-md ds2-5-body-link" data-author-id="53176588" href="https://huji.academia.edu/DavidGokhman"><img alt="Profile image of David Gokhman" class="ds-work-card--author-avatar" src="https://0.academia-photos.com/53176588/15230742/15905539/s65_david.gokhman.jpg" />David Gokhman</a><a class="ds-work-card--author js-wsj-grid-card-author ds2-5-body-md ds2-5-body-link" data-author-id="907564" href="https://univie.academia.edu/Song%C3%BClAlpaslanRoodenberg"><img alt="Profile image of Songül Alpaslan-Roodenberg" class="ds-work-card--author-avatar" src="https://0.academia-photos.com/907564/335660/164663941/s65_song_l.alpaslan-roodenberg.jpg" />Songül Alpaslan-Roodenberg</a><a class="ds-work-card--author js-wsj-grid-card-author ds2-5-body-md ds2-5-body-link" data-author-id="36529252" href="https://upf.academia.edu/CARLESLALUEZAFOX"><img alt="Profile image of CARLES LALUEZA-FOX" class="ds-work-card--author-avatar" src="https://0.academia-photos.com/36529252/11541473/12871786/s65_carles.lalueza-fox.jpg" />CARLES LALUEZA-FOX</a></div><div class="ds-work-card--detail"><div class="ds-work-card--work-metadata"><div class="ds-work-card--work-metadata__stat"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">visibility</span><p class="ds2-5-body-sm" id="work-metadata-view-count">…</p></div><div class="ds-work-card--work-metadata__stat"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">description</span><p class="ds2-5-body-sm">1 page</p></div><div class="ds-work-card--work-metadata__stat"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">link</span><p class="ds2-5-body-sm">1 file</p></div></div><script>(async () => { const workId = 44278503; 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However, identifying changes to regulatory elements that underlie human-specific traits has proven very challenging. Here, we use 63 reconstructed and experimentally measured DNA methylation maps of ancient and present-day humans, as well as of six chimpanzees, to detect differentially methylated regions that likely emerged in modern humans after the split from Neanderthals and Denisovans. We show that genes associated with face and vocal tract anatomy went through particularly extensive methylation changes. Specifically, we identify widespread hypermethylation in a network of face-and voice-associated genes (SOX9, ACAN, COL2A1, NFIX and XYLT1). We propose that these repression patterns appeared after the split from Neanderthals and Denisovans, and that they might have played a key role in shaping the modern human face and vocal tract.</p><div class="ds-work-card--button-container"><div class="primary-buttons "><button class="ds2-5-button js-swp-download-button" data-signup-modal="{"location":"continue-reading-button--work-card","attachmentId":64657110,"attachmentType":"pdf","workUrl":"https://www.academia.edu/44278503/Differential_DNA_methylation_of_vocal_and_facial_anatomy_genes_in_modern_humans"}"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">description</span>See full PDF</button><button class="ds2-5-button ds2-5-button--secondary js-swp-download-button" data-signup-modal="{"location":"download-pdf-button--work-card","attachmentId":64657110,"attachmentType":"pdf","workUrl":"https://www.academia.edu/44278503/Differential_DNA_methylation_of_vocal_and_facial_anatomy_genes_in_modern_humans"}"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">download</span>Download PDF</button></div></div><div class="ds-signup-banner-trigger-container"><div class="ds-signup-banner-trigger ds-signup-banner-trigger-control"></div></div><div class="ds-signup-banner ds-signup-banner-control"><div id="ds-signup-banner-close-button"><button class="ds2-5-button ds2-5-button--secondary ds2-5-button--inverse"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">close</span></button></div><div class="ds-signup-banner-ctas" data-impression-entity-id="44278503" data-impression-entity-type="2" data-impression-source="signup-banner"><img src="//a.academia-assets.com/images/academia-logo-capital-white.svg" /><h4 class="ds2-5-heading-serif-sm">Sign up for access to the world's latest research</h4><button class="ds2-5-button ds2-5-button--inverse ds2-5-button--full-width js-swp-download-button" data-signup-modal="{"location":"signup-banner"}">Sign up for free<span class="material-symbols-outlined" style="font-size: 20px" translate="no">arrow_forward</span></button></div><div class="ds-signup-banner-divider"></div><div class="ds-signup-banner-reasons"><div class="ds-signup-banner-reasons-item"><span class="material-symbols-outlined" style="font-size: 24px" translate="no">check</span><span>Get notified about relevant papers</span></div><div class="ds-signup-banner-reasons-item"><span class="material-symbols-outlined" style="font-size: 24px" translate="no">check</span><span>Save papers to use in your research</span></div><div class="ds-signup-banner-reasons-item"><span class="material-symbols-outlined" style="font-size: 24px" translate="no">check</span><span>Join the discussion with peers</span></div><div class="ds-signup-banner-reasons-item"><span class="material-symbols-outlined" style="font-size: 24px" translate="no">check</span><span>Track your impact</span></div></div></div><script>(() => { // Set up signup banner show/hide behavior: // 1. 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However, identifying regulatory changes that underlie human-specific traits has proven very challenging. Here, we use 63 DNA methylation maps of ancient and present-day humans, as well as of six chimpanzees, to detect differentially methylated regions that emerged in modern humans after the split from Neanderthals and Denisovans. We show that genes affecting the face and vocal tract went through particularly extensive methylation changes. Specifically, we identify widespread hypermethylation in a network of face- and voice-affecting genes (SOX9, ACAN, COL2A1, NFIX and XYLT1). We propose that these repression patterns appeared after the split from Neanderthals and Denisovans, and that they might have played a key role in shaping the modern human face and vocal tract.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Genes Affecting Vocal and Facial Anatomy Went Through Extensive Regulatory Divergence in Modern Humans","attachmentId":81505032,"attachmentType":"pdf","work_url":"https://www.academia.edu/72667433/Genes_Affecting_Vocal_and_Facial_Anatomy_Went_Through_Extensive_Regulatory_Divergence_in_Modern_Humans","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/72667433/Genes_Affecting_Vocal_and_Facial_Anatomy_Went_Through_Extensive_Regulatory_Divergence_in_Modern_Humans"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="1" data-entity-id="47983219" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/47983219/Extensive_Regulatory_Changes_in_Genes_Affecting_Vocal_and_Facial_Anatomy_Separate_Modern_Humans_from_Neanderthals_and_Denisovans">Extensive Regulatory Changes in Genes Affecting Vocal and Facial Anatomy Separate Modern Humans from Neanderthals and Denisovans</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="31311108" href="https://eva-mpg.academia.edu/GenevieveHousman">Genevieve Housman</a></div><p class="ds-related-work--abstract ds2-5-body-sm">Changes in gene regulation are broadly accepted as key drivers of phenotypic differences between closely related species. However, identifying regulatory changes that shaped human-specific traits is a very challenging task. Here, we use &gt;60 DNA methylation maps of ancient and present-day human groups, as well as six chimpanzee maps, to detect regulatory changes that emerged in modern humans after the split from Neanderthals and Denisovans. We show that genes affecting vocalization and facial features went through particularly extensive methylation changes. Specifically, we identify silencing patterns in a network of genes (SOX9, ACAN, COL2A1 and NFIX), and propose that they might have played a role in the reshaping of the human face, and in forming the 1:1 vocal tract configuration that is considered optimal for speech. Our results provide insights into the molecular mechanisms that may have shaped the modern human face and voice, and suggest that they arose after the split from ...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Extensive Regulatory Changes in Genes Affecting Vocal and Facial Anatomy Separate Modern Humans from Neanderthals and Denisovans","attachmentId":66831610,"attachmentType":"pdf","work_url":"https://www.academia.edu/47983219/Extensive_Regulatory_Changes_in_Genes_Affecting_Vocal_and_Facial_Anatomy_Separate_Modern_Humans_from_Neanderthals_and_Denisovans","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/47983219/Extensive_Regulatory_Changes_in_Genes_Affecting_Vocal_and_Facial_Anatomy_Separate_Modern_Humans_from_Neanderthals_and_Denisovans"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="2" data-entity-id="63237451" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/63237451/The_interplay_between_DNA_methylation_and_sequence_divergence_in_recent_human_evolution">The interplay between DNA methylation and sequence divergence in recent human evolution</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="57011350" href="https://independent.academia.edu/HugoFern%C3%A1ndezBellon">Hugo Fernández-Bellon</a></div><p class="ds-related-work--metadata ds2-5-body-xs">2015</p><p class="ds-related-work--abstract ds2-5-body-sm">DNA methylation is a key regulatory mechanism in mammalian genomes. Despite the increasing knowledge about this epigenetic modification, the understanding of human epigenome evolution is in its infancy. We used whole genome bisulfite sequencing to study DNA methylation and nucleotide divergence between human and great apes. We identified 360 and 210 differentially hypo- and hypermethylated regions (DMRs) in humans compared to non-human primates and estimated that 20% and 36% of these regions, respectively, were detectable throughout several human tissues. Human DMRs were enriched for specific histone modifications and contrary to expectations, the majority were located distal to transcription start sites, highlighting the importance of regions outside the direct regulatory context. We also found a significant excess of endogenous retrovirus elements in human-specific hypomethylated regions suggesting their association with local epigenetic changes. We also reported for the first tim...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"The interplay between DNA methylation and sequence divergence in recent human evolution","attachmentId":75730401,"attachmentType":"pdf","work_url":"https://www.academia.edu/63237451/The_interplay_between_DNA_methylation_and_sequence_divergence_in_recent_human_evolution","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/63237451/The_interplay_between_DNA_methylation_and_sequence_divergence_in_recent_human_evolution"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="3" data-entity-id="12945345" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/12945345/Dynamics_of_DNA_Methylation_in_Recent_Human_and_Great_Ape_Evolution">Dynamics of DNA Methylation in Recent Human and Great Ape Evolution</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="32130521" href="https://independent.academia.edu/MarcosFernandezcallejo">Marcos Fernandez-callejo</a></div><p class="ds-related-work--metadata ds2-5-body-xs">PLoS Genetics, 2013</p><p class="ds-related-work--abstract ds2-5-body-sm">DNA methylation is an epigenetic modification involved in regulatory processes such as cell differentiation during development, X-chromosome inactivation, genomic imprinting and susceptibility to complex disease. However, the dynamics of DNA methylation changes between humans and their closest relatives are still poorly understood. We performed a comparative analysis of CpG methylation patterns between 9 humans and 23 primate samples including all species of great apes (chimpanzee, bonobo, gorilla and orangutan) using Illumina Methylation450 bead arrays. Our analysis identified ,800 genes with significantly altered methylation patterns among the great apes, including ,170 genes with a methylation pattern unique to human. Some of these are known to be involved in developmental and neurological features, suggesting that epigenetic changes have been frequent during recent human and primate evolution. We identified a significant positive relationship between the rate of coding variation and alterations of methylation at the promoter level, indicative of co-occurrence between evolution of protein sequence and gene regulation. In contrast, and supporting the idea that many phenotypic differences between humans and great apes are not due to amino acid differences, our analysis also identified 184 genes that are perfectly conserved at protein level between human and chimpanzee, yet show significant epigenetic differences between these two species. We conclude that epigenetic alterations are an important force during primate evolution and have been under-explored in evolutionary comparative genomics.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Dynamics of DNA Methylation in Recent Human and Great Ape Evolution","attachmentId":45832658,"attachmentType":"pdf","work_url":"https://www.academia.edu/12945345/Dynamics_of_DNA_Methylation_in_Recent_Human_and_Great_Ape_Evolution","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/12945345/Dynamics_of_DNA_Methylation_in_Recent_Human_and_Great_Ape_Evolution"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="4" data-entity-id="28358778" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/28358778/Reconstructing_the_DNA_Methylation_Maps_of_the_Neandertal_and_the_Denisovan">Reconstructing the DNA Methylation Maps of the Neandertal and the Denisovan</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="53176588" href="https://huji.academia.edu/DavidGokhman">David Gokhman</a></div><p class="ds-related-work--abstract ds2-5-body-sm">Ancient DNA sequencing has recently provided high-coverage archaic human genomes. However, the evolution of epigenetic regulation along the human lineage remains largely unexplored. We reconstructed the full DNA methylation maps of the Neandertal and the Denisovan by harnessing the natural degradation processes of methylated and unmethylated cytosines. Comparing these ancient methylation maps to those of present-day humans, we identified ~2000 differentially methylated regions (DMRs). Particularly, we found substantial methylation changes in the HOXD cluster that may explain anatomical differences between archaic and present-day humans. Additionally, we found that DMRs are significantly more likely to be associated with diseases. This study provides insight into the epigenetic landscape of our closest evolutionary relatives and opens a window to explore the epigenomes of extinct species.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Reconstructing the DNA Methylation Maps of the Neandertal and the Denisovan","attachmentId":48693168,"attachmentType":"pdf","work_url":"https://www.academia.edu/28358778/Reconstructing_the_DNA_Methylation_Maps_of_the_Neandertal_and_the_Denisovan","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/28358778/Reconstructing_the_DNA_Methylation_Maps_of_the_Neandertal_and_the_Denisovan"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="5" data-entity-id="110955505" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/110955505/Epigenetic_information_from_ancient_DNA_provides_new_insights_into_human_evolution_Commentary_on_Gokhman_D_et_al_2014_Reconstructing_the_DNA_methylation_maps_of_the_Neanderthal_and_the_Denisovan_Science_344_523_527">Epigenetic information from ancient DNA provides new insights into human evolution. Commentary on Gokhman D et al. (2014): Reconstructing the DNA methylation maps of the Neanderthal and the Denisovan. Science 344:523-527</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="129658071" href="https://independent.academia.edu/SchneiderEberhard">Eberhard Schneider</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Brain, behavior and evolution, 2014</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Epigenetic information from ancient DNA provides new insights into human evolution. Commentary on Gokhman D et al. (2014): Reconstructing the DNA methylation maps of the Neanderthal and the Denisovan. Science 344:523-527","attachmentId":108611951,"attachmentType":"pdf","work_url":"https://www.academia.edu/110955505/Epigenetic_information_from_ancient_DNA_provides_new_insights_into_human_evolution_Commentary_on_Gokhman_D_et_al_2014_Reconstructing_the_DNA_methylation_maps_of_the_Neanderthal_and_the_Denisovan_Science_344_523_527","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/110955505/Epigenetic_information_from_ancient_DNA_provides_new_insights_into_human_evolution_Commentary_on_Gokhman_D_et_al_2014_Reconstructing_the_DNA_methylation_maps_of_the_Neanderthal_and_the_Denisovan_Science_344_523_527"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="6" data-entity-id="6579837" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/6579837/2012_Zeng_Divergent_whole_genome_methylation_maps_of_human_and_chimpanzee_brains_reveal_epigenetic_basis_of_human_regulatory_evolution">2012-Zeng_Divergent whole-genome methylation maps of human and chimpanzee brains reveal epigenetic basis of human regulatory evolution</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="3459" href="https://emory.academia.edu/ToddMPreuss">Todd M Preuss</a></div><p class="ds-related-work--abstract ds2-5-body-sm">DNA methylation is a pervasive epigenetic DNA modification that strongly affects chromatin regulation and gene expression. To date, it remains largely unknown how patterns of DNA methylation differ between closely related species and whether such differences contribute to species-specific phenotypes. To investigate these questions, we generated nucleotide-resolution whole-genome methylation maps of the prefrontal cortex of multiple humans and chimpanzees. Levels and patterns of DNA methylation vary across individuals within species according to the age and the sex of the individuals. We also found extensive species-level divergence in patterns of DNA methylation and that hundreds of genes exhibit significantly lower levels of promoter methylation in the human brain than in the chimpanzee brain. Furthermore, we investigated the functional consequences of methylation differences in humans and chimpanzees by integrating data on gene expression generated with next-generation sequencing methods, and we found a strong relationship between differential methylation and gene expression. Finally, we found that differentially methylated genes are strikingly enriched with loci associated with neurological disorders, psychological disorders, and cancers. Our results demonstrate that differential DNA methylation might be an important molecular mechanism driving gene-expression divergence between human and chimpanzee brains and might potentially contribute to the evolution of disease vulnerabilities. Thus, comparative studies of humans and chimpanzees stand to identify key epigenomic modifications underlying the evolution of human-specific traits.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"2012-Zeng_Divergent whole-genome methylation maps of human and chimpanzee brains reveal epigenetic basis of human regulatory evolution","attachmentId":35498687,"attachmentType":"pdf","work_url":"https://www.academia.edu/6579837/2012_Zeng_Divergent_whole_genome_methylation_maps_of_human_and_chimpanzee_brains_reveal_epigenetic_basis_of_human_regulatory_evolution","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/6579837/2012_Zeng_Divergent_whole_genome_methylation_maps_of_human_and_chimpanzee_brains_reveal_epigenetic_basis_of_human_regulatory_evolution"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="7" data-entity-id="11553599" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/11553599/Divergent_whole_genome_methylation_maps_of_human_and_chimpanzee_brains_reveal_epigenetic_basis_of_human_regulatory_evolution">Divergent whole-genome methylation maps of human and chimpanzee brains reveal epigenetic basis of human regulatory evolution</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="28204026" href="https://columbia.academia.edu/JiaXiZeng">Jia Xi Zeng</a></div><p class="ds-related-work--metadata ds2-5-body-xs">American journal of human genetics, 2012</p><p class="ds-related-work--abstract ds2-5-body-sm">DNA methylation is a pervasive epigenetic DNA modification that strongly affects chromatin regulation and gene expression. To date, it remains largely unknown how patterns of DNA methylation differ between closely related species and whether such differences contribute to species-specific phenotypes. To investigate these questions, we generated nucleotide-resolution whole-genome methylation maps of the prefrontal cortex of multiple humans and chimpanzees. Levels and patterns of DNA methylation vary across individuals within species according to the age and the sex of the individuals. We also found extensive species-level divergence in patterns of DNA methylation and that hundreds of genes exhibit significantly lower levels of promoter methylation in the human brain than in the chimpanzee brain. Furthermore, we investigated the functional consequences of methylation differences in humans and chimpanzees by integrating data on gene expression generated with next-generation sequencing methods, and we found a strong relationship between differential methylation and gene expression. Finally, we found that differentially methylated genes are strikingly enriched with loci associated with neurological disorders, psychological disorders, and cancers. Our results demonstrate that differential DNA methylation might be an important molecular mechanism driving gene-expression divergence between human and chimpanzee brains and might potentially contribute to the evolution of disease vulnerabilities. Thus, comparative studies of humans and chimpanzees stand to identify key epigenomic modifications underlying the evolution of human-specific traits.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Divergent whole-genome methylation maps of human and chimpanzee brains reveal epigenetic basis of human regulatory evolution","attachmentId":46633839,"attachmentType":"pdf","work_url":"https://www.academia.edu/11553599/Divergent_whole_genome_methylation_maps_of_human_and_chimpanzee_brains_reveal_epigenetic_basis_of_human_regulatory_evolution","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/11553599/Divergent_whole_genome_methylation_maps_of_human_and_chimpanzee_brains_reveal_epigenetic_basis_of_human_regulatory_evolution"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="8" data-entity-id="2850739" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/2850739/A_Genome_Wide_Study_of_DNA_Methylation_Patterns_and_Gene_Expression_Levels_in_Multiple_Human_and_Chimpanzee_Tissues">A Genome-Wide Study of DNA Methylation Patterns and Gene Expression Levels in Multiple Human and Chimpanzee Tissues</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="715136" href="https://chicago.academia.edu/AthmaPai">Athma Pai</a></div><p class="ds-related-work--metadata ds2-5-body-xs">2011</p><p class="ds-related-work--abstract ds2-5-body-sm">The modification of DNA by methylation is an important epigenetic mechanism that affects the spatial and temporal regulation of gene expression. Methylation patterns have been described in many contexts within and across a range of species. However, the extent to which changes in methylation might underlie inter-species differences in gene regulation, in particular between humans and other primates, has not yet been studied.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"A Genome-Wide Study of DNA Methylation Patterns and Gene Expression Levels in Multiple Human and Chimpanzee Tissues","attachmentId":31012828,"attachmentType":"pdf","work_url":"https://www.academia.edu/2850739/A_Genome_Wide_Study_of_DNA_Methylation_Patterns_and_Gene_Expression_Levels_in_Multiple_Human_and_Chimpanzee_Tissues","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/2850739/A_Genome_Wide_Study_of_DNA_Methylation_Patterns_and_Gene_Expression_Levels_in_Multiple_Human_and_Chimpanzee_Tissues"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="9" data-entity-id="14885784" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/14885784/DNA_methylation_contributes_to_natural_human_variation">DNA methylation contributes to natural human variation</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="33865365" href="https://independent.academia.edu/JuanSandoval48">Juan Sandoval</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Genome Research, 2013</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"DNA methylation contributes to natural human variation","attachmentId":43806916,"attachmentType":"pdf","work_url":"https://www.academia.edu/14885784/DNA_methylation_contributes_to_natural_human_variation","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/14885784/DNA_methylation_contributes_to_natural_human_variation"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div></div></div><div class="ds-sticky-ctas--wrapper js-loswp-sticky-ctas hidden"><div class="ds-sticky-ctas--grid-container"><div class="ds-sticky-ctas--container"><button class="ds2-5-button js-swp-download-button" data-signup-modal="{"location":"continue-reading-button--sticky-ctas","attachmentId":64657110,"attachmentType":"pdf","workUrl":null}">See full PDF</button><button class="ds2-5-button ds2-5-button--secondary js-swp-download-button" data-signup-modal="{"location":"download-pdf-button--sticky-ctas","attachmentId":64657110,"attachmentType":"pdf","workUrl":null}"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">download</span>Download PDF</button></div></div></div><div class="ds-below-fold--grid-container"><div class="ds-work--container js-loswp-embedded-document"><div class="attachment_preview" data-attachment="Attachment_64657110" style="display: none"><div class="js-scribd-document-container"><div class="scribd--document-loading js-scribd-document-loader" style="display: block;"><img alt="Loading..." src="//a.academia-assets.com/images/loaders/paper-load.gif" /><p>Loading Preview</p></div></div><div style="text-align: center;"><div class="scribd--no-preview-alert js-preview-unavailable"><p>Sorry, preview is currently unavailable. You can download the paper by clicking the button above.</p></div></div></div></div><div class="ds-sidebar--container js-work-sidebar"><div class="ds-related-content--container"><h2 class="ds-related-content--heading">Related papers</h2><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="0" data-entity-id="55791283" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/55791283/Comparative_Methylome_Analyses_Identify_Epigenetic_Regulatory_Loci_of_Human_Brain_Evolution">Comparative Methylome Analyses Identify Epigenetic Regulatory Loci of Human Brain Evolution</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="51436218" href="https://independent.academia.edu/TzungFuHsieh">Tzung-Fu Hsieh</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Molecular biology and evolution, 2016</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Comparative Methylome Analyses Identify Epigenetic Regulatory Loci of Human Brain Evolution","attachmentId":71494937,"attachmentType":"pdf","work_url":"https://www.academia.edu/55791283/Comparative_Methylome_Analyses_Identify_Epigenetic_Regulatory_Loci_of_Human_Brain_Evolution","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" href="https://www.academia.edu/55791283/Comparative_Methylome_Analyses_Identify_Epigenetic_Regulatory_Loci_of_Human_Brain_Evolution"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" 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translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" href="https://www.academia.edu/85554833/Evolution_of_DNA_methylation_in_the_human_brain"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="3" data-entity-id="106008118" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/106008118/DNA_Methylation_Networks_Underlying_Mammalian_Traits">DNA Methylation Networks Underlying Mammalian Traits</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="41151987" href="https://independent.academia.edu/SchmittTodd">Todd Schmitt</a></div><p class="ds-related-work--metadata ds2-5-body-xs">2021</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"DNA Methylation Networks Underlying Mammalian Traits","attachmentId":105319252,"attachmentType":"pdf","work_url":"https://www.academia.edu/106008118/DNA_Methylation_Networks_Underlying_Mammalian_Traits","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" href="https://www.academia.edu/106008118/DNA_Methylation_Networks_Underlying_Mammalian_Traits"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" 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