Pineda A O, Ellington W R
Department of Biological Science and Institute of Molecular Biophysics, Florida State University, 32306-4370, Tallahassee, FL, USA.
Gene. 2001 Mar 7;265(1-2):115-21. doi: 10.1016/s0378-1119(01)00352-3.
Two major gene duplication events are thought to have taken place in the evolution of creatine kinases (CK) in the vertebrates - (1) the formation of distinct mitochondrial (MiCK) and cytoplasmic forms from the primordial gene and (2) subsequent formation of the sarcomeric (sar-) and ubiquitous (ubi-) isoforms of octameric MiCK and muscle (M) and brain (B) isoforms of dimeric, cytoplasmic CK. The genes of these two CK clades reflect a distant divergence as sar- and ubiMiCK genes consistently have nine protein-coding exons while M- and B-CK genes have seven protein-coding exons; these genes share only one common exon. CKs are also widely distributed in the invertebrates and it has recently been shown that MiCKs evolved well before the divergence of the major metazoan groups. In the present communication, we report the structure and topology of the gene for MiCK from the protostome marine worm Chaetopterus variopedatus. The protein-coding region of the gene for this primitive MiCK spans over 10 kb and consists of eight exons, the last five (E4-E8) have identical boundaries to the corresponding exons of sar- and ubiMiCK genes. Exon-3 of the C. variopedatus MiCK gene consists of the corresponding E3 and E4 of the vertebrate MiCKs with no intervening intron. E1 is longer and E2 is shorter in the polychaete MiCK gene than the counterpart sarcomeric and ubiquitous genes. The insertion of the intron in C. variopedatus E3 creating the two exons as well as the rearrangement of the intron between E1 and E2 must have occurred prior to or coincident with the duplication event creating the two vertebrate mitochondrial isoforms. Sarcomeric and ubiMiCKs display substantial differences from their invertebrate MiCK counterparts in properties relating to octamer stability and membrane binding. The evolutionary changes in gene topology may be a component of this functional progression.
在脊椎动物肌酸激酶（CK）的进化过程中，被认为发生了两次主要的基因复制事件：（1）从原始基因形成不同的线粒体（MiCK）和细胞质形式；（2）随后八聚体MiCK的肌节（sar-）和普遍存在（ubi-）同工型以及二聚体细胞质CK的肌肉（M）和脑（B）同工型的形成。这两个CK进化枝的基因反映出遥远的分歧，因为sar-和ubiMiCK基因始终有9个蛋白质编码外显子，而M-和B-CK基因有7个蛋白质编码外显子；这些基因仅共享一个共同的外显子。CK在无脊椎动物中也广泛分布，最近研究表明MiCK在主要后生动物类群分化之前就已经进化。在本通讯中，我们报道了原口海洋蠕虫多毛纲盘管虫（Chaetopterus variopedatus）中MiCK基因的结构和拓扑结构。这种原始MiCK基因的蛋白质编码区域跨度超过10 kb，由8个外显子组成，最后5个（E4-E8）与sar-和ubiMiCK基因的相应外显子具有相同的边界。多毛纲盘管虫MiCK基因的外显子3由脊椎动物MiCK的相应E3和E4组成，没有中间内含子。与对应的肌节和普遍存在的基因相比，多毛纲MiCK基因中的E1更长，E2更短。在多毛纲盘管虫E3中插入内含子从而产生两个外显子，以及E1和E2之间内含子的重排，一定发生在产生两种脊椎动物线粒体同工型的复制事件之前或与之同时发生。肌节和ubiMiCK在与八聚体稳定性和膜结合相关的特性上与其无脊椎动物MiCK对应物有很大差异。基因拓扑结构的进化变化可能是这种功能进化的一个组成部分。
