<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>13</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Kim, Kwondo</style></author><author><style face="normal" font="default" size="100%">Pfennig, Aaron</style></author><author><style face="normal" font="default" size="100%">Syed, Sabriya A.</style></author><author><style face="normal" font="default" size="100%">Moskwa, Nicholas</style></author><author><style face="normal" font="default" size="100%">Oliveira, Nélio A.J.</style></author><author><style face="normal" font="default" size="100%">Pham, Quynh-Mai</style></author><author><style face="normal" font="default" size="100%">Hallast, Pille</style></author><author><style face="normal" font="default" size="100%">Yilmaz, Feyza</style></author><author><style face="normal" font="default" size="100%">McDonough, Justin A.</style></author><author><style face="normal" font="default" size="100%">Norton, Heather L.</style></author><author><style face="normal" font="default" size="100%">Akey, Joshua M.</style></author><author><style face="normal" font="default" size="100%">Lee, Charles</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">A Denisovan-derived Alu insertion in OCA2 contributes to pigmentation diversity in present-day Melanesians</style></title></titles><dates><year><style  face="normal" font="default" size="100%">2026</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2026/03/18</style></date></pub-dates></dates><urls><web-urls><url><style face="normal" font="default" size="100%">https://www.biorxiv.org/content/10.64898/2026.03.18.712481v1</style></url></web-urls></urls><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;&lt;meta charset=&quot;UTF-8&quot; /&gt;Modern humans inherited DNA from Neanderthals and Denisovans, but the contribution of introgressed structural variants (SVs) to present-day human phenotypes and adaptation remains poorly understood. Here, we used a graph-genome approach to genotype 96,277 SVs in 3,332 present-day humans and three high-coverage archaic hominin genomes, identifying 153 candidate introgressed SVs. These SVs are enriched for signatures of local adaptation compared to non-introgressed SVs (&lt;em&gt;p-value&lt;/em&gt;&amp;nbsp;= 3.04 &amp;times; 10&lt;sup&gt;-7&lt;/sup&gt;). Among these, we focused on a Denisovan-derived&amp;nbsp;&lt;em&gt;Alu&lt;/em&gt;&amp;nbsp;insertion located in intron 18 of&amp;nbsp;&lt;em&gt;OCA2&lt;/em&gt;, a gene central to pigmentation. This introgressed&amp;nbsp;&lt;em&gt;Alu&lt;/em&gt;&amp;nbsp;insertion is most frequently observed (&amp;gt; 60%) in Indigenous people from Bougainville Island of Melanesia, and is significantly associated with increased skin pigmentation in this region. To assess its functional impact, the&amp;nbsp;&lt;em&gt;Alu&lt;/em&gt;&amp;nbsp;insertion was introduced into human induced pluripotent stem cells (iPSCs), which were subsequently differentiated into melanocytes. Melanocytes harboring the&amp;nbsp;&lt;em&gt;Alu&lt;/em&gt;&amp;nbsp;insertion demonstrated elevated&amp;nbsp;&lt;em&gt;OCA2&lt;/em&gt;expression, increased pigmentation, and higher levels of enhancer activity compared to controls. Collectively, these findings highlight introgressed SVs as a significant source of adaptive and phenotypic diversity in modern humans and implicate the Denisovan-derived&amp;nbsp;&lt;em&gt;Alu&lt;/em&gt;insertion in&amp;nbsp;&lt;em&gt;OCA2&lt;/em&gt;&amp;nbsp;in pigmentation variation among present-day Melanesian populations.&lt;/p&gt;
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