The Impact of Population Bottlenecks on Microbial Adaptation

LeClair, Joshua S.; Wahl, Lindi M.

doi:10.1007/s10955-017-1924-6

Cited by 30 publications

(26 citation statements)

References 65 publications

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“…With bottleneck sizes of 10-200, our model is consistent with a parameter regime in which the pathogen is able to improve or maintain fitness. However, if only one or two virions found each infection (McCrone et al 2018), the theoretical expectation would be that viral fitness should decline due to the accumulation of deleterious mutations [see LeClair and Wahl (2017) for review]. An interesting speculation is that the founding dose may in fact be one-to-two virions during seasonal IAV epidemics in temperate zones, but could be two orders of magnitude larger in tropical regions (Xue et al 2018).…”

Section: Discussionmentioning

confidence: 99%

Effects of Transmission Bottlenecks on the Diversity of Influenza A Virus

2018

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We investigate the fate of de novo mutations that occur during the in-host replication of a pathogenic virus, predicting the probability that such mutations are passed on during disease transmission to a new host. Using influenza A virus as a model organism, we develop a life-history model of the within-host dynamics of the infection, deriving a multitype branching process with a coupled deterministic model to capture the population of available target cells. We quantify the fate of neutral mutations and mutations affecting five life-history traits: clearance, attachment, budding, cell death, and eclipse phase timing. Despite the severity of disease transmission bottlenecks, our results suggest that in a single transmission event, several mutations that appeared de novo in the donor are likely to be transmitted to the recipient. Even in the absence of a selective advantage for these mutations, the sustained growth phase inherent in each disease transmission cycle generates genetic diversity that is not eliminated during the transmission bottleneck.

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Section: Discussionmentioning

confidence: 99%

Effects of Transmission Bottlenecks on the Diversity of Influenza A Virus

2018

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“…This effect also 409 increases the eventual fixation probability of the beneficial allele. Fluctuations in 410 population size are known to reduce the fixation probability of beneficial 411 mutations [2,62,63], especially because reductions in population size can lead to an 412 increase in the power of drift and rapid elimination of genetic variation [64]. Empirical 413 work regularly shows faster adaptation in populations that undergo less severe 414 bottlenecks [65][66][67].…”

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confidence: 99%

“…Empirical 413 work regularly shows faster adaptation in populations that undergo less severe 414 bottlenecks [65][66][67]. Although many theoretical studies consider the effect of population 415 bottlenecks on the fate of mutations [62], most assume that these fluctuations in 416 population size are caused by factors outside the control of the organism [63,64], 417 although there are exceptions [22,68,69]. An intriguing exception is a previous 418 theoretical study, which has found that phenotypic plasticity can decrease the severity 419 of population bottlenecks, thus increasing standing genetic variation [22].…”

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confidence: 99%

Gene expression noise can promote the fixation of beneficial mutations in fluctuating environments

Schmutzer

Wagner

2020

Preprint

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Nongenetic phenotypic variation can either speed up or slow down adaptive evolution. We show that it can speed up evolution in environments in which available carbon and energy sources change over time. To this end, we use an experimentally validated model of Escherichia coli growth on two alternative carbon sources, glucose and acetate. On the superior carbon source (glucose), all cells achieve high growth rates, while on the inferior carbon source (acetate) only a small fraction of the population manages to initiate growth. Consequently, populations experience a bottleneck when the environment changes from the superior to the inferior carbon source. Growth on the inferior carbon source depends on a circuit under the control of a transcription factor that is repressed in the presence of the superior carbon source. We show that noise in the expression of this transcription factor can increase the probability that cells start growing on the inferior carbon source. In doing so, it can decrease the severity of the bottleneck and increase mean population fitness whenever this fitness is low. A modest amount of noise can also enhance the fitness effects of a beneficial allele. It can accelerate the spreading of such an allele, increase its likelihood of going to fixation, and reduce its fixation time. Central to the adaptation-enhancing principle we identify is the ability of noise to mitigate population bottlenecks. Because such bottlenecks are frequent in fluctuating environments, and because fluctuating environments themselves are ubiquitous, this principle may apply to a broad range of environments and organisms.

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“…However, for such small bottlenecks, stochasticity would significantly matter. Reducing the bottleneck size has been shown to generally increase the extinction probability in other contexts, but sometimes has the opposite effect (Schreiber et al 2016;LeClair and Wahl 2018). The details of transmission play an important part in this effect.…”

Section: Discussionmentioning

confidence: 99%

Antibody‐mediated crosslinking of gut bacteria hinders the spread of antibiotic resistance

et al. 2019

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The body is home to a diverse microbiota, mainly in the gut. Resistant bacteria are selected by antibiotic treatments, and once resistance becomes widespread in a population of hosts, antibiotics become useless. Here, we develop a multiscale model of the interaction between antibiotic use and resistance spread in a host population, focusing on an important aspect of within‐host immunity. Antibodies secreted in the gut enchain bacteria upon division, yielding clonal clusters of bacteria. We demonstrate that immunity‐driven bacteria clustering can hinder the spread of a novel resistant bacterial strain in a host population. We quantify this effect both in the case where resistance preexists and in the case where acquiring a new resistance mutation is necessary for the bacteria to spread. We further show that the reduction of spread by clustering can be countered when immune hosts are silent carriers, and are less likely to get treated, and/or have more contacts. We demonstrate the robustness of our findings to including stochastic within‐host bacterial growth, a fitness cost of resistance, and its compensation. Our results highlight the importance of interactions between immunity and the spread of antibiotic resistance, and argue in the favor of vaccine‐based strategies to combat antibiotic resistance.

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The Impact of Population Bottlenecks on Microbial Adaptation

Cited by 30 publications

References 65 publications

Effects of Transmission Bottlenecks on the Diversity of Influenza A Virus

Effects of Transmission Bottlenecks on the Diversity of Influenza A Virus

Gene expression noise can promote the fixation of beneficial mutations in fluctuating environments

Antibody‐mediated crosslinking of gut bacteria hinders the spread of antibiotic resistance

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