Université Pierre et Marie Curie, UMR 7138-Systématique, Adaptation, Evolution, Case 5, 7 Quai Saint-Bernard, Bâtiment A, 4e étage, 75005, Paris, France.
J Mol Evol. 2009 Dec;69(6):635-56. doi: 10.1007/s00239-009-9302-x.
Enamelin (ENAM) plays an important role in the mineralization of the forming enamel matrix. We have performed an evolutionary analysis of mammalian ENAM to identify highly conserved residues or regions that could have important function (selective pressure), to predict mutations that could be associated with amelogenesis imperfecta in humans, and to identify possible adaptive evolution of ENAM during 200 million years ago of mammalian evolution. In order to fulfil these objectives, we obtained 36-ENAM sequences that are representative of the mammalian lineages. Our results show a remarkably high conservation pattern in the region of the 32-kDa fragment of ENAM, especially its phosphorylation, glycosylation, and proteolytic sites. In primates and rodents we also identified several sites under positive selection, which could indicate recent evolutionary changes in ENAM function. Furthermore, the analysis of the unusual signal peptide provided new insights on the possible regulation of ENAM secretion, a hypothesis that should be tested in the near future. Taken together, these findings improve our understanding of ENAM evolution and provide new information that would be useful for further investigation of ENAM function as well as for the validation of mutations leading to amelogenesis imperfecta.
釉原蛋白（ENAM）在形成釉基质的矿化过程中起着重要作用。我们对哺乳动物的 ENAM 进行了进化分析，以鉴定高度保守的残基或区域，这些区域可能具有重要功能（选择压力），预测可能与人类牙釉质不全相关的突变，并确定在 2 亿年前哺乳动物进化过程中 ENAM 可能发生的适应性进化。为了实现这些目标，我们获得了 36 种代表哺乳动物谱系的 ENAM 序列。我们的结果显示，ENAM 的 32kDa 片段区域，尤其是其磷酸化、糖基化和蛋白水解位点，具有非常高的保守模式。在灵长类动物和啮齿类动物中，我们还鉴定出几个处于正选择下的位点，这可能表明 ENAM 功能的近期进化变化。此外，对异常信号肽的分析提供了关于 ENAM 分泌可能调控的新见解，这一假说应在不久的将来进行验证。总之，这些发现增进了我们对 ENAM 进化的理解，并提供了新的信息，这将有助于进一步研究 ENAM 功能以及验证导致牙釉质不全的突变。
