Muller's ratchet decreases fitness of a DNA-based microbe
Muller's ratchet decreases fitness of a DNA-based microbe
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DOI：
10.1073/pnas.93.2.906
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发表时间：
1996-01-23
影响因子：
11.1
通讯作者：
Hughes, D
中科院分区：
文献类型：
--
作者：
Andersson, DI;Hughes, D
Muller 提出，无性生物体将不可避免地积累有害突变，导致突变负荷的增加和最小突变类别的不可阻挡的、棘轮状的损失 [Muller, H. J. (1964) Mutat, Res. 1, 2-9], Muller 棘轮对真实群体的作用仅在 RNA 病毒中得到了实验证明。然而，这些情况是例外，因为RNA病毒的突变率极高。我们检查了穆勒棘轮是否在鼠伤寒沙门氏菌（一种具有更典型基因组突变率的基于DNA的生物体）中起作用。细胞在预计会导致高遗传漂变的条件下进行无性生长，并确定了突变负荷的增加，鼠伤寒沙门氏菌在这些条件下积累了突变，以致在1700代后，测试的444个谱系中的1%遭受了明显的适应性丧失，这通过生长速率下降来确定。这些结果表明，在缺乏性行为和高遗传漂变的情况下，遗传机制（例如反向突变或补偿突变）无法补偿有害突变的积累。此外，我们测量了营养缺陷型的出现，这使我们能够计算出每代每个碱基对约 0.3-1.5 x 10(-9) 个突变的平均自发突变率。该比率是针对迄今为止研究的最大遗传目标（约 200 个基因的集合）进行测量的。
Muller proposed that an asexual organism will inevitably accumulate deleterious mutations, resulting in an increase of the mutational load and an inexorable, ratchet-like, loss of the least mutated class [Muller, H. J. (1964) Mutat, Res. 1, 2-9], The operation of Muller's ratchet on real populations has been experimentally demonstrated only in RNA viruses. However, these cases are exceptional in that the mutation rates of the RNA viruses are extremely high, We have examined whether Muller's ratchet operates in Salmonella typhimurium, a DNA-based organism with a more typical genomic mutation rate. Cells were grown asexually under conditions expected to result in high genetic drift, and the increase in mutational load was determined, S. typhimurium accumulated mutations under these conditions such that after 1700 generations, 1% of the 444 lineages tested had suffered an obvious loss of fitness, as determined by decreased growth rate. These results suggest that in the absence of sex and with high genetic drift, genetic mechanisms, such as back or compensatory mutations, cannot compensate for the accumulation of deleterious mutations. In addition, we measured the appearance of auxotrophs, which allowed us to calculate an average spontaneous mutation rate of approximately 0.3-1.5 x 10(-9) mutations per base pair per generation. This rate is measured for the largest genetic target studied so far, a collection of about 200 genes.