Periodic variation of mutation rates in bacterial genomes associated with replication timing

Dillon, Marcus M.; Sung, Way; Lynch, Michael; Cooper, Vaughn S.

doi:10.1101/195818

Cited by 5 publications

(10 citation statements)

References 73 publications

(97 reference statements)

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“…Because of this tradeoff, any mechanism increasing the speed of a polymerase is expected to reduce its accuracy as well. Our analysis of the wave length of these oscillations supports that this pattern originates from a process synchronized with the cell cycle [18], whose activity alters the replisome function. An alternative explanation is that the oscillations ).…”

Section: Discussionsupporting

confidence: 71%

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Speed fluctuations of bacterial replisomes

Bhat¹,

Hauf

Plessy

et al. 2021

Preprint

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Replisomes are multi-protein complexes that replicate genomes with remarkable speed and accuracy. Despite their importance, the dynamics of replisomes along the genome is poorly characterised, especially in vivo. In this paper, we link the replisome dynamics with the DNA abundance distribution measured in an exponentially growing bacterial population. Our approach permits to accurately infer the replisome dynamics along the genome from deep sequencing measurements. As an application, we experimentally measured the DNA abundance distribution in Escherichia coli populations growing at different temperatures. We find that the average replisome speed increases nearly five-fold between 17°C and 37°C. Further, we observe wave-like variations of the replisome speed along the genome. These variations are correlated with previously observed variations of the mutation rate along the genome. We interpret this correlation as a speed--error trade-off and discuss its possible dynamical origin. Our approach has the potential to elucidate replication dynamics in E. coli mutants and in other bacterial species.

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Section: Discussionsupporting

confidence: 71%

“…Our fitted speed oscillations are reminiscent of a previously observed wave-like pattern in the mutation rate along the genome of different bacterial species [18,17]. For S1.…”

Section: Oscillating Speed Modelsupporting

confidence: 74%

Speed fluctuations of bacterial replisomes

Bhat¹,

Hauf

Plessy

et al. 2021

Preprint

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“…These experiments have provided us with key insights into mutational events of an organism. These insights include (a) the overall mutation rate (Caballero & Keightley, 1998, Kibota & Lynch, 1996, (b) the general mutational pattern (Kraemer et al, 2017, Estes et al, 2004, Dillon et al, 2018, Ann-Marie Waldvogel, 2020, (c) estimating the shape of the distribution of fitness effects of mutations (Bondel et al, 2019, Bosshard et al, 2017, Mrudula Sane, 2020.…”

Section: Introductionmentioning

confidence: 99%

Selection in a growing bacterial/yeast colony biases results of mutation accumulation experiments

Mahilkar

Saini

2021

Preprint

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Mutations provide the raw material for natural selection to act. Therefore, understanding the variety and relative frequency of different type of mutations is critical to understanding the nature of genetic diversity in a population. Mutation accumulation (MA) experiments have been used in this context to estimate parameters defining mutation rates, distribution of fitness effects (DFE), and spectrum of mutations. MA experiments performed with organisms such as Drosophila have an effective population size of one. However, in MA experiments with bacteria and yeast, a single founder is allowed to grow to a size of a colony (~108). The effective population size in these experiments is of the order of 10. In this scenario, while it is assumed that natural selection plays a minimal role in dictating the dynamics of colony growth and therefore, the MA experiment; this effect has not been tested explicitly. In this work, we simulate colony growth and perform an MA experiment, and demonstrate that selection ensures that, in an MA experiment, fraction of all mutations that are beneficial is over represented by a factor greater than two. The DFE of beneficial and deleterious mutations are accurately captured in an MA experiment. We show that the effect of selection in a growing colony varies non-monotonically and that, in the face of natural selection dictating an MA experiment, estimates of mutation rate of an organism is not trivial. We perform experiments with 160 MA lines of E. coli, and demonstrate that rate of change of mean fitness is a non-monotonic function of the colony size, and that selection acts differently in different sectors of a growing colony. Overall, we demonstrate that the results of MA experiments need to be revisited taking into account the action of selection in a growing colony.

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“…Mutation has been described as the 'quantum force' of biology 1 : pervasive throughout the tree of life, fundamental basis of evolution and notoriously difficult to measure. Evidence for the variation of mutation rates (µ) has been accumulating for a century, with pioneering investigations in Drosophila dating back to the 1930s 2,3 and more recent studies estimating the variability of µ in microorganisms [4][5][6] , plants [7][8][9] , invertebrates [10][11][12][13][14] as well as vertebrates [15][16][17] . On the intraspecific level, the spontaneous µ was often claimed to be a species-specific constant 18 .…”

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confidence: 99%

Temperature-dependence of spontaneous mutation rates

Waldvogel

Pfenninger

2020

Preprint

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Mutation is the source of genetic variation and the fundament of evolution. At the inter-phase of ecology and evolution, temperature has long been suggested to have a direct impact on realised spontaneous mutation rates. The question is whether mutation rates can be a species-specific constant under variable environmental conditions, such as variation of the ambient temperature. By combining mutation accumulation with whole genome sequencing in a multicellular organism, we provide empirical support to reject this null hypothesis. Instead mutation rates depend on temperature in a U-shaped manner with increasing rates towards both temperature extremes. This relation has important implications for mutation dependent processes in molecular evolution, processes shaping the evolution of mutation rates and even the evolution of biodiversity as such.

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Periodic variation of mutation rates in bacterial genomes associated with replication timing

Cited by 5 publications

References 73 publications

Speed fluctuations of bacterial replisomes

Speed fluctuations of bacterial replisomes

Selection in a growing bacterial/yeast colony biases results of mutation accumulation experiments

Temperature-dependence of spontaneous mutation rates

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