Rates Of Spontaneous Mutation

不同生物体的自发突变率差别很大。我们之前已经描述了基因组突变率，这是某些广泛的有机体群体的特征。例如，核病毒每次复制的基因组突变率为0.1？1，接近生存所需的最大值。基于8种非常不同的生物，基于dna的微生物的特征基因组突变率约为每次复制0.003。然而，在生长在75℃的古生菌中，突变率约为0.00075，碱基对替换的比例低于所有其他以dna为基础的生物。我们假设，平均错义突变在高温下具有更大的有害影响。因此，进化压力会降低碱基替换突变率。这一假设的一个预测是，嗜热真细菌也会显示出碱基对替换的频率降低，而中温古细菌则不会，目前正在对此类生物进行研究。在另一项工作中，我们正在研究在随机分布上具有比预期更多突变的突变，这一领域很快将成为我们的主要重点。

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 based on eight very diverse organisms. In the Archaeon Sulfolobus acidocaldarius growing at 75 degrees C, however, the mutation rate is about 0.00075 and 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.