Andrés-Mateos Eva, Cruces Jesús, Renart Jaime, Solís-Garrido Luisa M, Serantes Rocío, de Lucas-Cerrillo Ana M, Montiel Carmen
Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid, Arzobispo Morcillo 4, 28029-Madrid, Spain.
Gene. 2006 Sep 15;380(1):54-61. doi: 10.1016/j.gene.2006.06.003. Epub 2006 Jun 22.
A small expansion of a CAG repeat domain in exon 47 of the human CACNA1A gene, which codes for the pore-forming alpha1A subunit of P/Q-type Ca2+ channels, causes spinocerebellar ataxia type-6. Only the human alpha1A protein has been demonstrated to contain the poly(Q) tract, although this locus has also recently been detected in ape genomes. To our knowledge, no further information has been published on other mammal species. Here, we have cloned the full-length alpha1A subunit in a non-primate species, the cow. The results have made it possible to explore the exon organization of the bovine CACNA1A gene as well as the splice alpha1A isoforms expressed by bovine chromaffin cells. We found a splice variant of the protein that, as in humans, also contains a polymorphic poly(Q) tract. Based on this result and using data from different Genome Databases, we performed an interspecies comparison of exon 47 and discovered that the poly(Q) tract is present in all the species studied, with the exception of primitive fish and rodents. Our results provide insight into the evolution of the CAG repeat tract at the C-terminus coding region of the CACNA1A gene.
人类CACNA1A基因第47外显子中的CAG重复结构域发生小范围扩增，该基因编码P/Q型Ca2+通道的孔形成α1A亚基，会导致6型脊髓小脑共济失调。虽然最近在猿类基因组中也检测到了这个位点，但只有人类α1A蛋白被证明含有多聚谷氨酰胺（poly(Q)）序列。据我们所知，尚未有关于其他哺乳动物物种的进一步信息发表。在此，我们克隆了非灵长类物种牛的全长α1A亚基。这些结果使得探索牛CACNA1A基因的外显子组织以及牛嗜铬细胞表达的剪接α1A异构体成为可能。我们发现了一种蛋白质剪接变体，与人类一样，它也含有一个多态性的多聚谷氨酰胺序列。基于这一结果并利用来自不同基因组数据库的数据，我们对第47外显子进行了种间比较，发现除了原始鱼类和啮齿动物外，所有研究的物种中都存在多聚谷氨酰胺序列。我们的结果为深入了解CACNA1A基因C端编码区CAG重复序列的进化提供了线索。
