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Mutations in <jats:italic>ABCC6<\/jats:italic> are associated with human ectopic calcification disorders. To gain insight into its evolution and involvement in tissue calcification we conducted a comparative analysis of the <jats:italic>ABCC6<\/jats:italic> gene and the related gene <jats:italic>ABCC1<\/jats:italic> from invertebrates to vertebrates where a bony endoskeleton first evolved. Taking into consideration the role of <jats:italic>ABCC6<\/jats:italic> in ectopic calcification of human skin we analysed the involvement of both genes in the regeneration of scales, mineralized structures that develop in fish skin. The <jats:italic>ABCC6<\/jats:italic> gene was only found in bony vertebrate genomes and was absent from Elasmobranchs, Agnatha and from invertebrates. In teleost fish the <jats:italic>abcc6<\/jats:italic> gene duplicated but the two genes persisted only in some teleost genomes. Six disease causing amino acid mutations in human MRP6 are a normal feature of abcc6 in fish, suggesting they do not have a deleterious effect on the protein. After scale removal the <jats:italic>abcc6<\/jats:italic> (5 and 10 days) and <jats:italic>abcc1<\/jats:italic> (10 days) gene expression was up-regulated relative to the intact control skin and this coincided with a time of intense scale mineralization.<\/jats:p>","DOI":"10.1038\/s41598-018-24370-7","type":"journal-article","created":{"date-parts":[[2018,4,11]],"date-time":"2018-04-11T15:38:30Z","timestamp":1523461110000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Persistence of the ABCC6 genes and the emergence of the bony skeleton in vertebrates"],"prefix":"10.1038","volume":"8","author":[{"given":"Bruna","family":"Parreira","sequence":"first","affiliation":[]},{"given":"Jo\u00e3o C. 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