Elucidation of mechanism for fixation of mutations occurred in germ cells using medaka.

使用青鳉阐明生殖细胞中发生的突变固定机制。

基本信息

批准号：
11236204
负责人：
FUKAMACHI Shoji
金额：
$ 59.65万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research on Priority Areas
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2003
项目状态：
已结题

项目摘要

Germ-cell mutations caused in an organism are the source of genetic variation that is required for evolution, but at the same time, they may accumulate deleterious traits within a species. We have measured spontaneous germ-cell mutation rate at the pigmentation loci of the Medaka The resulting value was about 8×10^<-6>/locus/generation, indicating that vertebrate species share a common level of germ-cell mutation rate. Based on g-irradiation study, apoptosis of early differentiating spermatogonia with DNA damage proved to have an important role for regulation of overall mutation rate in male germ cells. In contrast mutation rate in female germ cells appeared to depend on fidelity of DNA repair. Next we found that spontaneous chromosomal breakages. and deletions are frequently caused in female germ cells of the Niigata wild population. Detailed analyses suggested that a novel mechanism for genome arrangement is involved in induction of germ-cell mutations in the wild populations of the Medaka Furthermore, we analysed the spectrum of spontaneous mutations by identifying spontaneous body-colour mutants. We positionally cloned responsible genes for the b, ci and i-3 mutants and identified they are caused by inversion, duplication or deletion of from several to dozens of nucleotides. Though others reported only insertions of transposon-like elements as a cause of spontaneous mutations on medaka genes (i, el, and rs-3), it is proved that that is not only the case. Meanwhile, because we isolated three pigmentation genes (functions of two of them are newly revealed by this study), we could provide new insights for developmental and evolutional studies of pigment cells.

在组织中引起的种系突变是进化所需的遗传变异的根源，但与此同时，它们可能会积累一个物种内的有害特征。我们已经在Medaka的色素沉着位点测量了赞助的种系突变率，结果值约为8×10^<-6>/lotus/Generation，这表明脊椎动物物种具有共同水平的生殖细胞突变率。基于G-iRradiation研究，事实证明，早期分化精子症和DNA损伤的凋亡对于调节男性生殖细胞的总体突变率具有重要作用。相反，女生殖细胞中的突变率似乎取决于DNA修复的保真度。接下来，我们发现赞助的染色体破裂。缺失经常是在尼加塔野生种群的女性生殖细胞中引起的。详细的分析表明，基因组排列的一种新型机制涉及Medaka野生种群中种系突变的诱导，我们通过识别发起的身体色突变体来分析了赞助突变的谱。我们对B，CI和I-3突变体的定位克隆负责的基因并确定它们是由倒数，重复或删除从几个到数十个核橄榄所引起的。尽管其他人仅报道了类似盆地样元素的插入，这是Medaka基因发起突变的原因（I，EL和RS-3），但事实证明，不仅是这种情况。同时，由于我们分离了三个色素沉着基因（这两个功能是由本研究新揭示的），因此我们可以为色素细胞的发育和进化研究提供新的见解。