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Published on: January 18, 2014
Muller's ratchet decreases fitness of a DNA-based microbe
1Department of Microbiology, Uppsala University, Biomedical Center, Sweden.
Abstract:
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.
Insights
Muller's ratchet, the accumulation of harmful mutations in asexual organisms, was observed in Salmonella typhimurium. This genetic load increased over 1700 generations, demonstrating a loss of fitness in some lineages.
Area of Science:
- Evolutionary Biology
- Microbiology
- Genetics
Background:
- Muller's ratchet theory posits that asexual reproduction leads to irreversible accumulation of deleterious mutations.
- Experimental evidence for Muller's ratchet is primarily from RNA viruses with exceptionally high mutation rates.
- The operation of Muller's ratchet in DNA-based organisms with typical mutation rates remains less understood.
Purpose of the Study:
- To investigate the operation of Muller's ratchet in Salmonella typhimurium, a DNA-based bacterium with a standard mutation rate.
- To determine if genetic drift in asexual populations of S. typhimurium leads to increased mutational load.
- To calculate the spontaneous mutation rate in S. typhimurium under conditions favoring genetic drift.
Main Methods:
- Asexual cultivation of Salmonella typhimurium under conditions promoting high genetic drift.
- Monitoring of fitness changes, specifically growth rate, across multiple lineages over 1700 generations.
- Measurement of auxotroph appearance to estimate the spontaneous mutation rate across approximately 200 genes.
Main Results:
- Salmonella typhimurium accumulated deleterious mutations over 1700 generations of asexual growth.
- One percent of tested lineages exhibited a significant loss of fitness due to accumulated mutations.
- The calculated spontaneous mutation rate was approximately 0.3-1.5 x 10^-9 mutations per base pair per generation.
Conclusions:
- Muller's ratchet operates in DNA-based organisms like S. typhimurium under conditions of asexual reproduction and high genetic drift.
- Compensatory or back mutations are insufficient to counteract the accumulation of deleterious mutations in these conditions.
- The study provides experimental validation of Muller's ratchet in a model organism with a typical mutation rate.
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