Rates Of Spontaneous Mutation

工作总结：生物间的自发突变率差别很大。我们以前已经描述了几种基因组突变率，这些突变率是某些广泛生物群体的特征。(1)基于dna的微生物的特征性突变率约为0.003 /基因组复制。在75℃下生长的Archeon Sulfolobus acidocalarius中，突变率接近0.003，但碱基对替换的比例低于其他所有dna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取代的突变率。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）突变的比例在嗜热生物中比在嗜热生物中要低。另一个预测是，嗜热真细菌也会显示碱基对取代的频率降低，而嗜热古菌则不会。这些预测现在正在经受考验。(2)利用烟草花叶病毒在携带TMV转基因的宿主中生长，获得了核糖体病毒的第一个突变谱，该转基因可以补充804碱基基因的缺陷，从而促进病毒颗粒在细胞间的传播。谱中最显著的方面是携带多种突变的突变体比例很高，远远超过基于突变频率的预测。结果表明，不可遗传的、短暂的超突变性显著地促进了该核核糖病毒的突变。

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.