title: Inactivation of C4orf26 in toothless placental mammals.
abstract: Previous studies have reported inactivated copies of six enamel-related genes (AMBN, AMEL, AMTN, ENAM, KLK4, MMP20) and one dentin-related gene (DSPP) in one or more toothless vertebrates and/or vertebrates with enamelless teeth, thereby providing evidence that these genes are enamel or tooth-specific with respect to their critical functions that are maintained by natural selection. Here, we employ available genome sequences for edentulous and enamelless mammals to evaluate the enamel specificity of four genes (WDR72, SLC24A4, FAM83H, C4orf26) that have been implicated in amelogenesis imperfecta, a condition in which proper enamel formation is abrogated during tooth development. Coding sequences for WDR72, SCL24A4, and FAM83H are intact in four edentulous taxa (Chinese pangolin, three baleen whales) and three taxa (aardvark, nine-banded armadillo, Hoffmann's two-toed sloth) with enamelless teeth, suggesting that these genes have critical functions beyond their involvement in tooth development. By contrast, genomic data for C4orf26 reveal inactivating mutations in pangolin and bowhead whale as well as evidence for deletion of this gene in two minke whale species. Hybridization capture of exonic regions and PCR screens provide evidence for inactivation of C4orf26 in eight additional baleen whale species. However, C4orf26 is intact in all three species with enamelless teeth that were surveyed, as well as in 95 additional mammalian species with enamel-capped teeth. Estimates of selection intensity suggest that dN/dS ratios on branches leading to taxa with enamelless teeth are similar to the dN/dS ratio on branches leading to taxa with enamel-capped teeth. Based on these results, we conclude that C4orf26 is tooth-specific, but not enamel-specific, with respect to its essential functions that are maintained by natural selection. A caveat is that an alternative splice site variant, which translates exon 3 in a different reading frame, is putatively functional in Catarrhini and may have evolved an additional role in this primate clade.
authors.affiliation: Department of Biology, University of California, Riverside, CA 92521, USA. Electronic address: mark.springer@ucr.edu.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Springer
authors.affiliation: Department of Biology, University of California, Riverside, CA 92521, USA; Department of Biology, San Diego State University, San Diego, CA 92182, USA.
authors.forename: James
authors.initials: J
authors.lastname: Starrett
authors.affiliation: Southwest Fisheries Science Center, National Marine Fisheries Service, National Oceanic and Atmospheric Administration, La Jolla, CA 92037, USA; Scripps Institution of Oceanography, University of California, San Diego, La Jolla, CA 92037, USA.
authors.forename: Phillip A
authors.initials: PA
authors.lastname: Morin
authors.affiliation: Department of Biology, University of California, Riverside, CA 92521, USA; Department of Biology, San Diego State University, San Diego, CA 92182, USA.
authors.forename: Agnese
authors.initials: A
authors.lastname: Lanzetti
authors.affiliation: Department of Biology, University of California, Riverside, CA 92521, USA.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Hayashi
authors.affiliation: Department of Biology, University of California, Riverside, CA 92521, USA.
authors.forename: John
authors.initials: J
authors.lastname: Gatesy
mesh_terms: D000567:Amelogenesis Imperfecta / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D003743:Dental Enamel / Q000254:growth & development*; D005091:Exons; D005260:Female; D020868:Gene Silencing; D050437:Genes, Developmental; D008322:Mammals / Q000235:genetics / Q000254:growth & development*; D008969:Molecular Sequence Data; D010920:Placenta; D011247:Pregnancy; D012641:Selection, Genetic; D012689:Sequence Homology, Nucleic Acid; D014070:Tooth / Q000254:growth & development*; D014907:Whales / Q000235:genetics
keywords: C4orf26; Cetacea; Mysticeti; Pholidota; Pseudogenes; Tooth genes