title: Molecular evolution of amelogenin in mammals.
abstract: An evolutionary analysis of mammalian amelogenin, the major protein of forming enamel, was conducted by comparison of 26 sequences (including 14 new ones) representative of the main mammalian lineages. Amelogenin shows highly conserved residues in the hydrophilic N- and C-terminal regions. The central hydrophobic region (most of exon 6) is more variable, but it has conserved a high amount of proline and glutamine located in triplets, PXQ, indicating that these residues play an important role. This region evolves more rapidly, and is less constrained, than the other well-conserved regions, which are subjected to strong constraints. The comparison of the substitution rates in relation to the CpG richness confirmed that the highly conserved regions are subjected to strong selective pressures. The amino acids located at important sites and the residues known to lead to amelogenesis imperfecta when substituted were present in all sequences examined. Evolutionary analysis of the variable region of exon 6 points to a particular zone, rich in either amino acid insertion or deletion. We consider this region a hot spot of mutation for the mammalian amelogenin. In this region, numerous triplet repeats (PXQ) have been inserted recently and independently in five lineages, while most of the hydrophobic exon 6 region probably had its origin in several rounds of triplet insertions, early in vertebrate evolution. The putative ancestral DNA sequence of the mammalian amelogenin was calculated using a maximum likelihood approach. The putative ancestral protein was composed of 177 residues. It already contained all important amino acid positions known to date, its hydrophobic variable region was rich in proline and glutamine, and it contained triplet repeats PXQ as in the modern sequences.
authors.affiliation: FRE2696, Equipe Evolution & Développement du Squelette, Université Paris 6, Paris, France.
authors.forename: Sidney
authors.initials: S
authors.lastname: Delgado
authors.forename: Marc
authors.initials: M
authors.lastname: Girondot
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Sire
mesh_terms: D053523:Amelogenin; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017124:Conserved Sequence / Q000235:genetics; D018899:CpG Islands / Q000235:genetics; D003746:Dental Enamel Proteins / Q000737:chemistry / Q000235:genetics*; D019143:Evolution, Molecular; D005091:Exons / Q000235:genetics; D014644:Genetic Variation; D005973:Glutamine / Q000235:genetics; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008322:Mammals / Q000235:genetics*; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D009154:Mutation; D010802:Phylogeny; D011392:Proline / Q000235:genetics; D020449:Repetitive Sequences, Amino Acid / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D012641:Selection, Genetic; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid
chemical_list: D053523:Amelogenin; D003746:Dental Enamel Proteins; D005973:Glutamine; D011392:Proline