{"id":702,"date":"2024-06-04T12:20:58","date_gmt":"2024-06-04T15:20:58","guid":{"rendered":"https:\/\/ucthp.hospitalelcalafate.gob.ar\/?p=702"},"modified":"2024-06-04T12:27:18","modified_gmt":"2024-06-04T15:27:18","slug":"evolutionary-and-functional-analyses-of-lrp5-in-archaic-and-extant-modern-humans","status":"publish","type":"post","link":"https:\/\/ucthp.hospitalelcalafate.gob.ar\/?p=702","title":{"rendered":"Evolutionary and functional analyses of LRP5 in archaic and extant modern humans"},"content":{"rendered":"\n<p><mark style=\"background-color:rgba(0, 0, 0, 0)\" class=\"has-inline-color has-ast-global-color-3-color\">Neus Roca-Ayats,\u00a0Iago Maceda,\u00a0Carlos David Bruque,\u00a0N\u00faria Mart\u00ednez-Gil,\u00a0Nat\u00e0lia Garcia-Giralt,\u00a0M\u00f3nica Cozar,\u00a0Leonardo Mellibovsky,\u00a0Wim Van Hul,\u00a0Oscar Lao,\u00a0Daniel Grinberg,\u00a0Susanna Balcells<\/mark><\/p>\n\n\n\n<h2 class=\"wp-block-heading\">Abstract<\/h2>\n\n\n\n<p><strong>Background <\/strong>The human lineage has undergone a postcranial skeleton gracilization (i.e. lower bone mass and strength relative to body size) compared to other primates and archaic populations such as the Neanderthals. This gracilization has been traditionally explained by diferences in the mechanical load that our ancestors exercised.<br>However, there is growing evidence that gracilization could also be genetically infuenced.<br><strong>Results<\/strong> We have analyzed the LRP5 gene, which is known to be associated with high bone mineral density conditions, from an evolutionary and functional point of view. Taking advantage of the published genomes of archaic Homo populations, our results suggest that this gene has a complex evolutionary history both between archaic and living humans and within living human populations. In particular, we identifed the presence of diferent selective pressures in archaics and extant modern humans, as well as evidence of positive selection in the African and South East Asian populations from the 1000 Genomes Project. Furthermore, we observed a very limited evidence of archaic<br>introgression in this gene (only at three haplotypes of East Asian ancestry out of the 1000 Genomes), compatible with a general erasing of the fngerprint of archaic introgression due to functional diferences in archaics compared to extant modern humans. In agreement with this hypothesis, we observed private mutations in the archaic genomes that we experimentally validated as putatively increasing bone mineral density. In particular, four of fve archaic missense mutations afecting the frst \u03b2-propeller of LRP5 displayed enhanced Wnt pathway activation, of which two also displayed reduced negative regulation.<br><strong>Conclusions<\/strong> In summary, these data suggest a genetic component contributing to the understanding of skeletal<br>diferences between extant modern humans and archaic Homo populations.<br><strong>Keywords <\/strong>LRP5, Bone mineral density, Neanderthal, Denisovan, Human evolution, Archaic introgression<\/p>\n\n\n\n<div class=\"wp-block-buttons is-layout-flex wp-block-buttons-is-layout-flex\">\n<div class=\"wp-block-button has-custom-width wp-block-button__width-100\"><a class=\"wp-block-button__link wp-element-button\" href=\"https:\/\/humgenomics.biomedcentral.com\/articles\/10.1186\/s40246-024-00616-6\" target=\"_blank\" rel=\"noreferrer noopener\">Ver Publicaci\u00f3n<\/a><\/div>\n<\/div>\n","protected":false},"excerpt":{"rendered":"<p>Neus Roca-Ayats,\u00a0Iago Maceda,\u00a0Carlos David Bruque,\u00a0N\u00faria Mart\u00ednez-Gil,\u00a0Nat\u00e0lia Garcia-Giralt,\u00a0M\u00f3nica Cozar,\u00a0Leonardo Mellibovsky,\u00a0Wim Van Hul,\u00a0Oscar Lao,\u00a0Daniel Grinberg,\u00a0Susanna Balcells Abstract Background The human lineage has undergone a postcranial skeleton gracilization (i.e. lower bone mass and strength relative to body size) compared to other primates and archaic populations such as the Neanderthals. This gracilization has been traditionally explained by diferences in [&hellip;]<\/p>\n","protected":false},"author":2,"featured_media":708,"comment_status":"closed","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"_eb_attr":"","_uag_custom_page_level_css":"","advgb_blocks_editor_width":"","advgb_blocks_columns_visual_guide":"","site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"footnotes":""},"categories":[11],"tags":[],"class_list":["post-702","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-publicaciones"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v23.3 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>Evolutionary and functional analyses of LRP5 in archaic and extant modern humans - UCT HP<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/ucthp.hospitalelcalafate.gob.ar\/?p=702\" \/>\n<meta property=\"og:locale\" content=\"es_ES\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Evolutionary and functional analyses of LRP5 in archaic and extant modern humans - UCT HP\" \/>\n<meta property=\"og:description\" content=\"Neus Roca-Ayats,\u00a0Iago Maceda,\u00a0Carlos David Bruque,\u00a0N\u00faria Mart\u00ednez-Gil,\u00a0Nat\u00e0lia Garcia-Giralt,\u00a0M\u00f3nica Cozar,\u00a0Leonardo Mellibovsky,\u00a0Wim Van Hul,\u00a0Oscar Lao,\u00a0Daniel Grinberg,\u00a0Susanna Balcells Abstract Background The human lineage has undergone a postcranial skeleton gracilization (i.e. lower bone mass and strength relative to body size) compared to other primates and archaic populations such as the Neanderthals. This gracilization has been traditionally explained by diferences in [&hellip;]\" \/>\n<meta property=\"og:url\" content=\"https:\/\/ucthp.hospitalelcalafate.gob.ar\/?p=702\" \/>\n<meta property=\"og:site_name\" content=\"UCT HP\" \/>\n<meta property=\"article:published_time\" content=\"2024-06-04T15:20:58+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2024-06-04T15:27:18+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/ucthp.hospitalelcalafate.gob.ar\/wp-content\/uploads\/2024\/06\/bmc.png\" \/>\n\t<meta property=\"og:image:width\" content=\"250\" \/>\n\t<meta property=\"og:image:height\" content=\"195\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/png\" \/>\n<meta name=\"author\" content=\"Mirtha\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Escrito por\" \/>\n\t<meta name=\"twitter:data1\" content=\"Mirtha\" \/>\n\t<meta name=\"twitter:label2\" content=\"Tiempo de lectura\" \/>\n\t<meta name=\"twitter:data2\" content=\"2 minutos\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\/\/schema.org\",\"@graph\":[{\"@type\":\"Article\",\"@id\":\"https:\/\/ucthp.hospitalelcalafate.gob.ar\/?p=702#article\",\"isPartOf\":{\"@id\":\"https:\/\/ucthp.hospitalelcalafate.gob.ar\/?p=702\"},\"author\":{\"name\":\"Mirtha\",\"@id\":\"https:\/\/ucthp.hospitalelcalafate.gob.ar\/#\/schema\/person\/cb3d81609139435146e1257936dc9b98\"},\"headline\":\"Evolutionary and functional analyses of LRP5 in archaic and extant modern humans\",\"datePublished\":\"2024-06-04T15:20:58+00:00\",\"dateModified\":\"2024-06-04T15:27:18+00:00\",\"mainEntityOfPage\":{\"@id\":\"https:\/\/ucthp.hospitalelcalafate.gob.ar\/?p=702\"},\"wordCount\":328,\"publisher\":{\"@id\":\"https:\/\/ucthp.hospitalelcalafate.gob.ar\/#organization\"},\"image\":{\"@id\":\"https:\/\/ucthp.hospitalelcalafate.gob.ar\/?p=702#primaryimage\"},\"thumbnailUrl\":\"https:\/\/ucthp.hospitalelcalafate.gob.ar\/wp-content\/uploads\/2024\/06\/bmc.png\",\"articleSection\":[\"publicaciones\"],\"inLanguage\":\"es\"},{\"@type\":\"WebPage\",\"@id\":\"https:\/\/ucthp.hospitalelcalafate.gob.ar\/?p=702\",\"url\":\"https:\/\/ucthp.hospitalelcalafate.gob.ar\/?p=702\",\"name\":\"Evolutionary and functional analyses of LRP5 in archaic and extant modern humans - 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This gracilization has been traditionally explained by diferences in&hellip;","coauthors":[],"tax_additional":{"categories":{"linked":["<a href=\"https:\/\/ucthp.hospitalelcalafate.gob.ar\/?cat=11\" class=\"advgb-post-tax-term\">publicaciones<\/a>"],"unlinked":["<span class=\"advgb-post-tax-term\">publicaciones<\/span>"]}},"comment_count":"0","relative_dates":{"created":"Publicado 2 a\u00f1os hace","modified":"Actualizado 2 a\u00f1os hace"},"absolute_dates":{"created":"Publicado el 4 de junio de 2024","modified":"Actualizado el 4 de junio de 2024"},"absolute_dates_time":{"created":"Publicado el 4 de junio de 2024 12:20 pm","modified":"Actualizado el 4 de junio de 2024 12:27 pm"},"featured_img_caption":"","series_order":"","_links":{"self":[{"href":"https:\/\/ucthp.hospitalelcalafate.gob.ar\/index.php?rest_route=\/wp\/v2\/posts\/702","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/ucthp.hospitalelcalafate.gob.ar\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/ucthp.hospitalelcalafate.gob.ar\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/ucthp.hospitalelcalafate.gob.ar\/index.php?rest_route=\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/ucthp.hospitalelcalafate.gob.ar\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=702"}],"version-history":[{"count":4,"href":"https:\/\/ucthp.hospitalelcalafate.gob.ar\/index.php?rest_route=\/wp\/v2\/posts\/702\/revisions"}],"predecessor-version":[{"id":707,"href":"https:\/\/ucthp.hospitalelcalafate.gob.ar\/index.php?rest_route=\/wp\/v2\/posts\/702\/revisions\/707"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/ucthp.hospitalelcalafate.gob.ar\/index.php?rest_route=\/wp\/v2\/media\/708"}],"wp:attachment":[{"href":"https:\/\/ucthp.hospitalelcalafate.gob.ar\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=702"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/ucthp.hospitalelcalafate.gob.ar\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=702"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/ucthp.hospitalelcalafate.gob.ar\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=702"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}