{"doi":"10.1038/s41586-024-07095-8","title":"On the genetic basis of tail-loss evolution in humans and apes","abstract":"Abstract The loss of the tail is among the most notable anatomical changes to have occurred along the evolutionary lineage leading to humans and to the ‘anthropomorphous apes’ 1–3 , with a proposed role in contributing to human bipedalism 4–6 . 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—inserted into an intron of the TBXT gene 7–9 —pairs 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 Tbxt , mimicking the expression pattern of its hominoid orthologue TBXT . Mice expressing both Tbxt isoforms exhibit a complete absence of the tail or a shortened tail depending on the relative abundance of Tbxt 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 Tbxt isoform develop neural tube defects, a condition that affects approximately 1 in 1,000 neonates in humans 10 . 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.","journal":"Nature","year":2024,"id":416623,"datarank":1.8863840263948504,"base_score":4.736198448394496,"endowment":4.736198448394496,"self_citation_contribution":0.7104297672591745,"citation_network_contribution":1.175954259135676,"self_endowment_contribution":0.7104297672591745,"citer_contribution":1.175954259135676,"corpus_percentile":null,"corpus_rank":null,"citation_count":113,"citer_count":100,"citers_with_citation_signal":61,"citers_with_endowment":61,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9467,"is_data_producer":true,"deposit_databanks":{"GEO":["GSE252279"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":49799,"name":"Weimin Zhang","orcid":"0000-0002-8836-1438","position":1,"is_corresponding":false},{"id":863187,"name":"Guisheng Zhao","orcid":"0000-0003-3276-7292","position":2,"is_corresponding":false},{"id":995190,"name":"Xinru Zhang","orcid":"0000-0002-0633-2888","position":3,"is_corresponding":false},{"id":207971,"name":"Jiangshan Bai","orcid":null,"position":4,"is_corresponding":false},{"id":438348,"name":"Ran Brosh","orcid":"0000-0001-9714-8623","position":5,"is_corresponding":false},{"id":804542,"name":"Aleksandra Wudzinska","orcid":"0000-0002-3143-7673","position":6,"is_corresponding":false},{"id":109140,"name":"Emily Huang","orcid":"0000-0002-9558-7814","position":7,"is_corresponding":false},{"id":974335,"name":"Hannah J. Ashe","orcid":null,"position":8,"is_corresponding":false},{"id":973922,"name":"Gwen Ellis","orcid":"0000-0003-2292-7264","position":9,"is_corresponding":false},{"id":700903,"name":"Maayan Pour","orcid":"0000-0003-1997-5193","position":10,"is_corresponding":false},{"id":854208,"name":"Yu Zhao","orcid":"0000-0003-4659-9832","position":11,"is_corresponding":false},{"id":983534,"name":"Camila Coelho","orcid":"0000-0003-0533-1370","position":12,"is_corresponding":false},{"id":79357,"name":"Yinan Zhu","orcid":"0000-0003-3189-5188","position":13,"is_corresponding":false},{"id":586074,"name":"Alexander Miller","orcid":"0000-0002-0662-9673","position":14,"is_corresponding":false},{"id":470118,"name":"Jeremy S. Dasen","orcid":"0000-0002-9434-874X","position":15,"is_corresponding":false},{"id":11626,"name":"Matthew T. Maurano","orcid":"0000-0002-2218-8628","position":16,"is_corresponding":false},{"id":455291,"name":"Sang Yong Kim","orcid":"0000-0001-7326-7505","position":17,"is_corresponding":false},{"id":49826,"name":"Jef D. Boeke","orcid":"0000-0001-5322-4946","position":18,"is_corresponding":false},{"id":58388,"name":"Itai Yanai","orcid":"0000-0002-8438-2741","position":19,"is_corresponding":false},{"id":804541,"name":"Bo Xia","orcid":"0000-0003-0929-7253","position":0,"is_corresponding":true}],"reference_count":65,"raw_metadata":null,"created_at":"2026-07-19T01:56:44.873714Z","pmid":"38418917","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}