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。我们以前描述了几个基因组突变率是某些广泛的生物体群体的特征。(1)基于DNA的微生物的特征突变率为每次基因组复制约0.003。在生长于75摄氏度的Archeon Sulfolobus acidocaldarius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，在进化过程中积累的错义突变与沉默（同义）突变的比率在嗜热生物中比在嗜温生物中要低。另一个预测是，嗜热真细菌也会显示碱基对替换频率降低，但嗜温古细菌不会。这些预测现在正在接受检验。(2)利用在携带TMV转基因的宿主中生长的烟草花叶病毒获得了核糖病毒的第一个突变谱，该TMV转基因补充了804碱基基因中的缺陷，该基因有利于病毒颗粒在细胞之间的传播。最值得注意的方面是携带多个突变的突变体的比例很高，远远超过基于突变频率的预测。结果表明，不可遗传的，短暂的超突变性在这种核糖病毒的突变中有显著的作用。

Summary of Work: Rates of spontaneous mutation vary greatly among organisms. We have previously described several genomic mutation rates that are characteristic of certain broad groups of organisms. (1) The characteristic mutation rate for DNA-based microbes is about 0.003 per genome replication. In the Archeon 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 the ratio of missense to silent (synonymous) mutations accumulating in the course of evolution would be lower in thermophiles than in mesophiles. Another prediction is that a thermophilic eubacterium would also show reduced frequencies of base-pair substitutions but that a mesophilic archaeon would not. These predictions are now being tested. (2) The first mutational spectrum for a ribovirus has been obtained using tobacco mosaic virus growing in a host carrying a TMV transgene that complements defects in the 804-base gene that facilitates the spread of virus particles between cells. The most remarkable aspect of the spectrum is the high proportion of mutants carrying multiple mutations, far in excess of predictions based on the mutant frequency. The results suggest that nonheritable, transitory hypermutability contributes strikingly to mutation in this ribovirus.