The Probability That Beneficial Mutations Are Lost in Populations With Periodic Bottlenecks

Wahl, Lindi M.; Gerrish, Philip J.

doi:10.1111/j.0014-3820.2001.tb00772.x

Cited by 107 publications

(93 citation statements)

References 14 publications

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“…Heffernan & Wahl (2002) incorporated the latter effect, assuming a Poisson distribution of offspring during the growth phase, and using a method based on the work of Ewens (1967). This model predicted a greater than 25 per cent reduction in the fixation probability for realistic experimental protocols, compared with that predicted by Wahl & Gerrish (2001).…”

Section: Population Bottlenecksmentioning

confidence: 99%

The fixation probability of beneficial mutations

Patwa

Wahl

2008

J. R. Soc. Interface.

211

215

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The fixation probability, the probability that the frequency of a particular allele in a population will ultimately reach unity, is one of the cornerstones of population genetics. In this review, we give a brief historical overview of mathematical approaches used to estimate the fixation probability of beneficial alleles. We then focus on more recent work that has relaxed some of the key assumptions in these early papers, providing estimates that have wider applicability to both natural and laboratory settings. In the final section, we address the possibility of future work that might bridge the gap between theoretical results to date and results that might realistically be applied to the experimental evolution of microbial populations. Our aim is to highlight the concrete, testable predictions that have arisen from the theoretical literature, with the intention of further motivating the invaluable interplay between theory and experiment.

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Section: Population Bottlenecksmentioning

confidence: 99%

The fixation probability of beneficial mutations

Patwa

Wahl

2008

J. R. Soc. Interface.

211

215

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“…This essentially gives the best chance for various mutations of different selective advantages to fix in a population. The ideal passage sizes calculated in these studies are relatively large (13.5% and 20%) (19,20). As mentioned previously, a larger passage size necessitates an increase in resources.…”

mentioning

confidence: 71%

“…Theoretical studies have looked at the effect of passage size on serially passaged batch culture adaptation and have resulted in various predictions of an ideal passage size, depending on the model used (19,20). The ideal passage sizes calculated are ideal from a mathematical standpoint.…”

mentioning

confidence: 99%

A Model for Designing Adaptive Laboratory Evolution Experiments

LaCroix

Palsson

Feist

2017

Appl Environ Microbiol

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The occurrence of mutations is a cornerstone of the evolutionary theory of adaptation, capitalizing on the rare chance that a mutation confers a fitness benefit. Natural selection is increasingly being leveraged in laboratory settings for industrial and basic science applications. Despite increasing deployment, there are no standardized procedures available for designing and performing adaptive laboratory evolution (ALE) experiments. Thus, there is a need to optimize the experimental design, specifically for determining when to consider an experiment complete and for balancing outcomes with available resources (i.e., laboratory supplies, personnel, and time). To design and to better understand ALE experiments, a simulator, ALEsim, was developed, validated, and applied to the optimization of ALE experiments. The effects of various passage sizes were experimentally determined and subsequently evaluated with ALEsim, to explain differences in experimental outcomes. Furthermore, a beneficial mutation rate of 10 Ϫ6.9 to 10 Ϫ8.4 mutations per cell division was derived. A retrospective analysis of ALE experiments revealed that passage sizes typically employed in serial passage batch culture ALE experiments led to inefficient production and fixation of beneficial mutations. ALEsim and the results described here will aid in the design of ALE experiments to fit the exact needs of a project while taking into account the resources required and will lower the barriers to entry for this experimental technique.IMPORTANCE ALE is a widely used scientific technique to increase scientific understanding, as well as to create industrially relevant organisms. The manner in which ALE experiments are conducted is highly manual and uniform, with little optimization for efficiency. Such inefficiencies result in suboptimal experiments that can take multiple months to complete. With the availability of automation and computer simulations, we can now perform these experiments in an optimized fashion and can design experiments to generate greater fitness in an accelerated time frame, thereby pushing the limits of what adaptive laboratory evolution can achieve. KEYWORDS Escherichia coli, adaptive evolution, evolutionary biologyA daptive laboratory evolution (ALE) has been performed in vitro for decades, and the field is expanding. ALE involves subjecting a population of organisms to a given environment, in the laboratory, and allowing natural selection to increase the overall fitness of the population. In laboratory settings, this is typically performed with organisms possessing short generation times. The basic principles governing ALE experiments are easily understood across a breadth of disciplines, which has led to its adoption in many laboratories (1, 2). The recent growth in the use of ALE can be attributed to the ease of access and decreasing costs of genome sequencing (3-5). Decreasing sequencing costs have led to increased investigation of genomic, transcriptomic, and additional data types over the course of evolution (5). Wh...

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“…We implemented a severe bottleneck of 50 to 100 cells per transfer, which has been shown to accelerate Muller's ratchet by increasing the stochasticity of the experiment and consequently the frequency of transferring and fixing deleterious mutations. A severe bottleneck also reduces the frequency of selective sweeps of beneficial mutations and the associated hitchhiking mutations (17)(18)(19)(50)(51)(52)(53). Periodic examination of mating abilities revealed no loss of conjugation capacity at the population level over the course of evolution.…”

Section: Resultsmentioning

confidence: 99%

“…Previous reports in the literature indicate that small effective population sizes and high mutation rates are much more sensitive to Muller's ratchet (55). Therefore, we used a small effective population size of (calculated with the harmonic mean [50]) ϳ120 and a mutator strain. However, we failed to observe mutational meltdown in any of our populations over the course of ϳ850 generations; a similar mutational meltdown experiment in yeast resulted in only one meltdown in a longer time frame (22).…”

Section: Discussionmentioning

confidence: 99%

Benefits of a Recombination-Proficient Escherichia coli System for Adaptive Laboratory Evolution

Peabody

Winkler

Fountain

et al. 2016

Appl Environ Microbiol

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Adaptive laboratory evolution typically involves the propagation of organisms asexually to select for mutants with the desired phenotypes. However, asexual evolution is prone to competition among beneficial mutations (clonal interference) and the accumulation of hitchhiking and neutral mutations. The benefits of horizontal gene transfer toward overcoming these known disadvantages of asexual evolution were characterized in a strain of Escherichia coli engineered for superior sexual recombination (genderless). Specifically, we experimentally validated the capacity of the genderless strain to reduce the mutational load and recombine beneficial mutations. We also confirmed that inclusion of multiple origins of transfer influences both the frequency of genetic exchange throughout the chromosome and the linkage of donor DNA. We built a simple kinetic model to estimate recombination frequency as a function of transfer size and relative genotype enrichment in batch transfers; the model output correlated well with the experimental data. Our results provide strong support for the advantages of utilizing the genderless strain over its asexual counterpart during adaptive laboratory evolution for generating beneficial mutants with reduced mutational load. IMPORTANCEOver 80 years ago Fisher and Muller began a debate on the origins of sexual recombination. Although many aspects of sexual recombination have been examined at length, experimental evidence behind the behaviors of recombination in many systems and the means to harness it remain elusive. In this study, we sought to experimentally validate some advantages of recombination in typically asexual Escherichia coli and determine if a sexual strain of E. coli can become an effective tool for strain development.

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The Probability That Beneficial Mutations Are Lost in Populations With Periodic Bottlenecks

Cited by 107 publications

References 14 publications

The fixation probability of beneficial mutations

The fixation probability of beneficial mutations

A Model for Designing Adaptive Laboratory Evolution Experiments

Benefits of a Recombination-Proficient Escherichia coli System for Adaptive Laboratory Evolution

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