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However, such constraints may be relaxed following gene duplication or when proteins are organized into structural and functional modules, opening avenues for evolutionary innovation. Here, we integrate expression and genomic data to investigate the evolutionary dynamics of\n                    <jats:italic>Hox<\/jats:italic>\n                    gene duplicates in the allotetraploid frog\n                    <jats:italic>Xenopus laevis<\/jats:italic>\n                    . Despite overall conservation across the\n                    <jats:italic>Hox<\/jats:italic>\n                    clusters, we find that\n                    <jats:italic>HoxB4L<\/jats:italic>\n                    has acquired expression during maternally regulated stages and is evolving under positive selection. Protein\u2010level changes include the number, length, and sequence of functionally important protein regions. Our results indicate that\n                    <jats:italic>HoxB4L<\/jats:italic>\n                    has escaped ancestral constraints and is undergoing maternal neofunctionalization as a result of cis\u2010regulatory divergence and structural protein modifications. These findings illustrate how transcription factors can overcome developmental constraints and contribute to novel functions during early development.\n                  <\/jats:p>","DOI":"10.1002\/jezb.70012","type":"journal-article","created":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T08:25:25Z","timestamp":1768292725000},"page":"141-151","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Escaping Constraints to Innovate: Maternal Neofunctionalization in a\n                    <i>HoxB4<\/i>\n                    Duplicate"],"prefix":"10.1002","volume":"346","author":[{"given":"J\u00falia de Lima","family":"Carvalho","sequence":"first","affiliation":[{"name":"Instituto de Biologia Universidade Federal da Bahia Salvador Bahia Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Caetano","family":"Silva\u2010Filho","sequence":"additional","affiliation":[{"name":"UNIESP Centro Universit\u00e1rio Cabedelo Para\u00edba Brazil"},{"name":"Afya Faculdade de Ci\u00eancias M\u00e9dicas da Para\u00edba Cabedelo Para\u00edba Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8018-0210","authenticated-orcid":false,"given":"Janaina Lima","family":"de Oliveira","sequence":"additional","affiliation":[{"name":"Instituto de Biologia Universidade Federal da Bahia Salvador Bahia Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,1,12]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07487-w"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1207726109"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkae1082"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4614-0659-4_6"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2226"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/376479a0"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0030245"},{"key":"e_1_2_8_9_1","volume-title":"From DNA to Diversity: Molecular Genetics and the Evolution of Animal Design","author":"Carroll S. 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