Richard Béatrice, Delgado Sidney, Gorry Philippe, Sire Jean-Yves
UFR d'Odontologie, 16 cours de la Marne, 33082 Bordeaux, France.
Arch Oral Biol. 2007 Nov;52(11):1026-31. doi: 10.1016/j.archoralbio.2007.06.001. Epub 2007 Jul 23.
Amelogenin gene (AMEL) encodes for a protein that plays important roles in the organization and structure of enamel. A recent evolutionary analysis of AMELX in mammals has revealed, aside to well-conserved 5' and 3' regions, a variable region located in the largest exon (exon 6), which strongly suggested the possible existence of polymorphism in human AMELX. A detailed analysis of this region was of fundamental importance for genetic studies. We have looked for variations in human AMELX exon 6 from 100 AMELX alleles in a randomized European population, using denaturing high-performance liquid chromatography (dHPLC). We also have looked for AMELX variants in databases, and compared this region in nine primates. There were no variations in the AMELX sequences analysed, but two synonymous single-nucleotide polymorphisms were found in databases. Alignment of the primate exon 6 sequences revealed that AMELX is highly constrained, as illustrated by 100% nucleotide identity found between humans and chimpanzee, and from 99.9 to 94.8% nucleotide identity in the other species. In contrast to what was suspected from the evolutionary analysis, we conclude that AMELX polymorphism should occur at low level in humans. This finding leads us to speculate that the high constraint observed in primate AMELX is related to its location on the X chromosome, and is due to selection at a single locus.
釉原蛋白基因（AMEL）编码一种在牙釉质的组织和结构中起重要作用的蛋白质。最近对哺乳动物中AMELX的进化分析表明，除了保守的5'和3'区域外，在最大的外显子（外显子6）中存在一个可变区域，这强烈暗示人类AMELX中可能存在多态性。对该区域进行详细分析对遗传学研究至关重要。我们使用变性高效液相色谱（dHPLC），在一个随机选取的欧洲人群中，对100个AMELX等位基因的人类AMELX外显子6中的变异进行了研究。我们还在数据库中查找了AMELX变体，并比较了9种灵长类动物的该区域。在所分析的AMELX序列中没有发现变异，但在数据库中发现了两个同义单核苷酸多态性。灵长类动物外显子6序列的比对显示，AMELX受到高度限制，如人类和黑猩猩之间的核苷酸同一性为100%，其他物种的核苷酸同一性在99.9%至94.8%之间。与进化分析所推测的情况相反，我们得出结论，人类AMELX多态性应该以低水平出现。这一发现使我们推测，在灵长类动物AMELX中观察到的高度限制与其在X染色体上的位置有关，并且是由于在单个位点上的选择所致。
