Piehler Armin P, Wenzel Jürgen J, Olstad Ole K, Haug Kari Bente Foss, Kierulf Peter, Kaminski Wolfgang E
R&D Group, Department of Clinical Chemistry, Ulleval University Hospital, 0407 Oslo, Norway.
BMC Mol Biol. 2006 Sep 12;7:28. doi: 10.1186/1471-2199-7-28.
During the past years, we and others discovered a series of human ATP-binding cassette (ABC) transporters, now referred to as ABC A-subfamily transporters. Recently, a novel testis-specific ABC A transporter, Abca17, has been cloned in rodent. In this study, we report the identification and characterization of the human ortholog of rodent Abca17.
The novel human ABC A-transporter gene on chromosome 16p13.3 is ubiquitously expressed with highest expression in glandular tissues and the heart. The new ABC transporter gene exhibits striking nucleotide sequence homology with the recently cloned mouse (58%) and rat Abca17 (51%), respectively, and is located in the syntenic region of mouse Abca17 indicating that it represents the human ortholog of rodent Abca17. However, unlike in the mouse, the full-length ABCA17 transcript (4.3 kb) contains numerous mutations that preclude its translation into a bona fide ABC transporter protein strongly suggesting that the human ABCA17 gene is a transcribed pseudogene (ABCA17P). We identified numerous alternative ABCA17P splice variants which are transcribed from two distinct transcription initiation sites. Genomic analysis revealed that ABCA17P borders on another ABC A-subfamily transporter - the lung surfactant deficiency gene ABCA3. Surprisingly, we found that both genes overlap at their first exons and are transcribed from opposite strands. This genomic colocalization and the observation that the ABCA17P and ABCA3 genes share significant homologies in several exons (up to 98%) suggest that both genes have evolved by gene duplication.
Our results demonstrate that ABCA17P and ABCA3 form a complex of overlapping genes in the human genome from which both non-coding and protein-coding ABC A-transporter RNAs are expressed. The fact that both genes overlap at their 5' ends suggests interdependencies in their regulation and may have important implications for the functional analysis of the disease gene ABCA3. Moreover, this is the first demonstration of the expression of a pseudogene and its parent gene from a common overlapping DNA region in the human genome.
在过去几年中，我们和其他研究人员发现了一系列人类ATP结合盒（ABC）转运蛋白，现在被称为ABC A亚家族转运蛋白。最近，一种新的睾丸特异性ABC A转运蛋白Abca17已在啮齿动物中克隆出来。在本研究中，我们报告了啮齿动物Abca17的人类同源物的鉴定和特征。
位于染色体16p13.3上的新型人类ABC A转运蛋白基因在全身广泛表达，在腺组织和心脏中表达最高。这个新的ABC转运蛋白基因分别与最近克隆的小鼠（58%）和大鼠Abca17（51%）具有显著的核苷酸序列同源性，并且位于小鼠Abca17的同线区域，表明它代表了啮齿动物Abca17的人类同源物。然而，与小鼠不同的是，全长ABCA17转录本（4.3 kb）包含许多突变，这些突变阻止其翻译成真正的ABC转运蛋白，这强烈表明人类ABCA17基因是一个转录假基因（ABCA17P）。我们鉴定了许多从两个不同转录起始位点转录的ABCA17P可变剪接变体。基因组分析显示，ABCA17P与另一个ABC A亚家族转运蛋白——肺表面活性物质缺乏基因ABCA3相邻。令人惊讶的是，我们发现这两个基因在其第一个外显子处重叠，并且从相反的链转录。这种基因组共定位以及ABCA17P和ABCA3基因在几个外显子中具有显著同源性（高达98%）的观察结果表明，这两个基因是通过基因复制进化而来的。
我们的结果表明，ABCA17P和ABCA3在人类基因组中形成了一个重叠基因复合体，从中表达非编码和蛋白质编码的ABC A转运蛋白RNA。这两个基因在其5'端重叠的事实表明它们在调控上相互依赖，可能对疾病基因ABCA3的功能分析具有重要意义。此外，这是首次证明人类基因组中一个假基因及其亲本基因从一个共同的重叠DNA区域表达。
