Rates Of Spontaneous Mutation

工作总结：自发突变的速率在不同生物体中差异很大。我们先前描述了基因组突变率，这是某些广泛的生物群体的特征。例如，核糖病毒的基因组突变率为0.1？1，接近与存活相容的最大值。基于DNA的微生物的特征基因组突变率为每次复制约0.003。由于这一规则的普遍性尚未在哺乳动物病毒病原体中得到检验，我们正在研究单纯疱疹病毒的突变过程。在75摄氏度下生长的硫化叶菌中，突变率接近0.003，但碱基对替换的比例低于所有其他基于DNA的生物。我们假设平均错义突变在高温下有更大的有害影响。因此，进化压力会降低碱基替换突变率。这一假说的一个预测是，嗜热真细菌也会显示出碱基对替换频率降低，而嗜温古细菌则不会，现在正在研究这种生物。在另一项工作中，我们正在研究在随机分布中具有比预期更多突变的突变体，这一领域将很快成为我们的主要焦点。

Summary of Work: Rates of spontaneous mutation vary greatly among organisms. We have previously described genomic mutation rates that are characteristic of certain broad groups of organisms. For instance, riboviruses have genomic mutation rates of 0.1?1 per replication, a value approaching the maximum compatible with survival. The characteristic genomic mutation rate for DNA-based microbes is about 0.003 per replication. Because the generality of this rule has not been tested in a mammalian viral pathogen, we are investigating the mutation process in herpes simplex virus. In the Archaeon Sulfolobus acidocaldarius growing at 75 degrees C, the mutation rate is close to 0.003 but the proportion of base-pair substitutions is lower than in all other DNA-based organisms. We hypothesized that the average missense mutation has a greater deleterious effect at high temperatures. As a result, evolutionary pressures would act to decrease base-substitution mutation rates. One prediction of this hypothesis is that a thermophilic eubacterium would also show reduced frequencies of base-pair substitutions while a mesophilic archaeon would not, and such organisms are now being investigated. In a separate line of work, we are investigating mutants that have more mutations than expected on a random distribution, and this area will soon be our major focus.