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However, the underlying molecular mechanism behind cetacean limb development remains poorly understood.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>In the present study, we explored the evolution of 16 limb-related genes and their cis-regulatory elements in cetaceans and compared them with that of other mammals. <jats:italic>TBX5<\/jats:italic>, a forelimb specific expression gene, was identified to have been under accelerated evolution in the ancestral branches of cetaceans. In addition, 32 cetacean-specific changes were examined in the SHH signaling network (<jats:italic>SHH<\/jats:italic>, <jats:italic>PTCH1<\/jats:italic>, <jats:italic>TBX5<\/jats:italic>, BMPs and <jats:italic>SMO<\/jats:italic>), within which mutations could yield webbed digits or an additional phalange. These findings thus suggest that the SHH signaling network regulates cetacean flipper formation. By contrast, the regulatory activity of the <jats:italic>SHH<\/jats:italic> gene enhancer\u2014ZRS in cetaceans\u2014was significantly lower than in mice, which is consistent with the cessation of <jats:italic>SHH<\/jats:italic> gene expression in the hindlimb bud during cetacean embryonic development. It was suggested that the decreased SHH activity regulated by enhancer ZRS might be one of the reasons for hindlimb degeneration in cetaceans. Interestingly, a parallel \/ convergent site (D42G) and a rapidly evolving CNE were identified in marine mammals in <jats:italic>FGF10<\/jats:italic> and <jats:italic>GREM1,<\/jats:italic> respectively, and shown to be essential to restrict limb bud size; this is molecular evidence explaining the convergence of flipper-forelimb and shortening or degeneration of hindlimbs in marine mammals.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>We did evolutionary analyses of 16 limb-related genes and their cis-regulatory elements in cetaceans and compared them with those of other mammals to provide novel insights into the molecular basis of flipper forelimb and hindlimb loss in cetaceans.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12864-022-09024-3","type":"journal-article","created":{"date-parts":[[2022,12,2]],"date-time":"2022-12-02T18:03:47Z","timestamp":1670004227000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Evolutionary genetics of flipper forelimb and hindlimb loss from limb development-related genes in cetaceans"],"prefix":"10.1186","volume":"23","author":[{"given":"Linxia","family":"Sun","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinghua","family":"Rong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xing","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenpeng","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qian","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenhua","family":"Ren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shixia","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,12,2]]},"reference":[{"issue":"2","key":"9024_CR1","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1007\/s12052-009-0135-2","volume":"2","author":"J Thewissen","year":"2009","unstructured":"Thewissen J, Cooper LN, George JC, Bajpai S. 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