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Yet, the genetic mechanism that facilitated tail-loss evolution in hominoids remains unknown. Here we present evidence that an individual insertion of an Alu element in the genome of the hominoid ancestor may have contributed to tail-loss evolution. We demonstrate that this Alu element\u2014inserted into an intron of the\n                    <jats:italic>TBXT<\/jats:italic>\n                    gene\n                    <jats:sup>7\u20139<\/jats:sup>\n                    \u2014pairs with a neighbouring ancestral Alu element encoded in the reverse genomic orientation and leads to a hominoid-specific alternative splicing event. To study the effect of this splicing event, we generated multiple mouse models that express both full-length and exon-skipped isoforms of\n                    <jats:italic>Tbxt<\/jats:italic>\n                    , mimicking the expression pattern of its hominoid orthologue\n                    <jats:italic>TBXT<\/jats:italic>\n                    . Mice expressing both\n                    <jats:italic>Tbxt<\/jats:italic>\n                    isoforms exhibit a complete absence of the tail or a shortened tail depending on the relative abundance of\n                    <jats:italic>Tbxt<\/jats:italic>\n                    isoforms expressed at the embryonic tail bud. These results support the notion that the exon-skipped transcript is sufficient to induce a tail-loss phenotype. Moreover, mice expressing the exon-skipped\n                    <jats:italic>Tbxt<\/jats:italic>\n                    isoform develop neural tube defects, a condition that affects approximately 1 in 1,000 neonates in humans\n                    <jats:sup>10<\/jats:sup>\n                    . Thus, tail-loss evolution may have been associated with an adaptive cost of the potential for neural tube defects, which continue to affect human health today.\n                  <\/jats:p>","DOI":"10.1038\/s41586-024-07095-8","type":"journal-article","created":{"date-parts":[[2024,2,28]],"date-time":"2024-02-28T12:04:44Z","timestamp":1709121884000},"page":"1042-1048","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":130,"title":["On the genetic basis of tail-loss evolution in humans and apes"],"prefix":"10.1038","volume":"626","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0929-7253","authenticated-orcid":false,"given":"Bo","family":"Xia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8836-1438","authenticated-orcid":false,"given":"Weimin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guisheng","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0633-2888","authenticated-orcid":false,"given":"Xinru","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangshan","family":"Bai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9714-8623","authenticated-orcid":false,"given":"Ran","family":"Brosh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3143-7673","authenticated-orcid":false,"given":"Aleksandra","family":"Wudzinska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Ashe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gwen","family":"Ellis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maayan","family":"Pour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4659-9832","authenticated-orcid":false,"given":"Yu","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila","family":"Coelho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinan","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy S.","family":"Dasen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2218-8628","authenticated-orcid":false,"given":"Matthew T.","family":"Maurano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang Y.","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5322-4946","authenticated-orcid":false,"given":"Jef D.","family":"Boeke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8438-2741","authenticated-orcid":false,"given":"Itai","family":"Yanai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,2,28]]},"reference":[{"key":"7095_CR1","doi-asserted-by":"crossref","unstructured":"Darwin, C. 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