Ahmed S, Sheng H, Niu L, Henderson E
Department of Zoology and Genetics, Signal Transduction Training Group, Iowa State University, Ames, Iowa 50011, USA.
Genetics. 1998 Oct;150(2):643-50. doi: 10.1093/genetics/150.2.643.
Telomere length is dynamic in many organisms. Genetic screens that identify mutants with altered telomere lengths are essential if we are to understand how telomere length is regulated in vivo. In Tetrahymena thermophila, telomeres become long at 30 degrees, and growth rate slows. A slow-growing culture with long telomeres is often overgrown by a variant cell type with short telomeres and a rapid-doubling rate. Here we show that this variant cell type with short telomeres is in fact a mutant with a genetic defect in telomere length regulation. One of these telomere growth inhibited forever (tgi) mutants was heterozygous for a telomerase RNA mutation, and this mutant telomerase RNA caused telomere shortening when overexpressed in wild-type cells. Several other tgi mutants were also likely to be heterozygous at their mutant loci, since they reverted to wild type when selective pressure for short telomeres was removed. These results illustrate that telomere length can regulate growth rate in Tetrahymena and that this phenomenon can be exploited to identify genes involved in telomere length regulation.
端粒长度在许多生物体中是动态变化的。如果我们想要了解端粒长度在体内是如何被调控的，那么识别端粒长度发生改变的突变体的遗传筛选至关重要。在嗜热四膜虫中，端粒在30摄氏度时长，生长速率减慢。具有长端粒的缓慢生长培养物常常会被具有短端粒和快速倍增速率的变异细胞类型过度生长。在此我们表明，这种具有短端粒的变异细胞类型实际上是一种在端粒长度调控方面存在遗传缺陷的突变体。这些端粒生长永远受抑制（tgi）突变体之一是端粒酶RNA突变的杂合子，并且这种突变的端粒酶RNA在野生型细胞中过表达时会导致端粒缩短。其他几个tgi突变体在其突变位点也可能是杂合的，因为当去除对短端粒的选择压力时，它们会回复为野生型。这些结果表明，端粒长度可以调控嗜热四膜虫的生长速率，并且这种现象可被用于鉴定参与端粒长度调控的基因。
