Kiff J E, Moerman D G, Schriefer L A, Waterston R H
Department of Genetics, Washington University School of Medicine, St. Louis, Missouri 63110.
Nature. 1988 Feb 18;331(6157):631-3. doi: 10.1038/331631a0.
The unc-22 gene of Caenorhabolitis elegans encodes a protein which is a component of the myosin-containing A-band of the worm's striated body-wall muscle. Among 51 revertants of a transposon-induced mutant, we have identified four which retain a barely detectable mutant phenotype. Molecular analysis shows that three of these have in-frame deletions of 1.0, 1.3 and 2.0 kilobases, whereas the fourth partial revertant and two other apparently complete revertants have small insertions. All these rearrangements involve coding sequence and, in the case of the deletions, result in polypeptides that are shorter than the wild-type protein. The region of the gene containing these rearrangements contains 10 copies of a motif recognized in other regions of the gene (our unpublished data). We suggest that one explanation for the minimally mutant phenotype associated with the deletions is that the size and the repeated nature of the unc-22 protein structure make it relatively tolerant of substitutions or deletions involving one or a small number of repeated motifs. These results could explain why in some human genetic diseases, such as Duchenne's muscular dystrophy, deletions can be associated with only mild forms of the disease.
秀丽隐杆线虫的unc-22基因编码一种蛋白质,该蛋白质是线虫横纹体壁肌肉中含肌球蛋白的A带的一个组成部分。在一个转座子诱导的突变体的51个回复突变体中,我们鉴定出了四个仍保留几乎无法检测到的突变表型的回复突变体。分子分析表明,其中三个有1.0、1.3和2.0千碱基的框内缺失,而第四个部分回复突变体和另外两个明显完全回复突变体有小的插入。所有这些重排都涉及编码序列,就缺失而言,会导致产生比野生型蛋白质短的多肽。包含这些重排的基因区域含有在该基因其他区域识别出的一个基序的10个拷贝(我们未发表的数据)。我们认为,与缺失相关的最小突变表型的一种解释是,unc-22蛋白质结构的大小和重复性质使其相对耐受涉及一个或少量重复基序的替换或缺失。这些结果可以解释为什么在一些人类遗传疾病中,如杜氏肌营养不良症,缺失可能仅与疾病的轻度形式相关。