Genomic investigations of evolutionary dynamics and epistasis in microbial evolution experiments

Jerison, Elizabeth R.; Desai, Michael M.

doi:10.1016/j.gde.2015.08.008

Cited by 62 publications

(50 citation statements)

References 91 publications

(65 reference statements)

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“…Epistasis is an important factor that can impose strong constraints on the adaptive process of bacterial populations [47,48]. This has been extensively studied in vitro [29,30,49,50] but only rarely in vivo [51].…”

Section: Discussionmentioning

confidence: 99%

A Mutational Hotspot and Strong Selection Contribute to the Order of Mutations Selected for during Escherichia coli Adaptation to the Gut

et al. 2016

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The relative role of drift versus selection underlying the evolution of bacterial species within the gut microbiota remains poorly understood. The large sizes of bacterial populations in this environment suggest that even adaptive mutations with weak effects, thought to be the most frequently occurring, could substantially contribute to a rapid pace of evolutionary change in the gut. We followed the emergence of intra-species diversity in a commensal Escherichia coli strain that previously acquired an adaptive mutation with strong effect during one week of colonization of the mouse gut. Following this first step, which consisted of inactivating a metabolic operon, one third of the subsequent adaptive mutations were found to have a selective effect as high as the first. Nevertheless, the order of the adaptive steps was strongly affected by a mutational hotspot with an exceptionally high mutation rate of 10−5. The pattern of polymorphism emerging in the populations evolving within different hosts was characterized by periodic selection, which reduced diversity, but also frequency-dependent selection, actively maintaining genetic diversity. Furthermore, the continuous emergence of similar phenotypes due to distinct mutations, known as clonal interference, was pervasive. Evolutionary change within the gut is therefore highly repeatable within and across hosts, with adaptive mutations of selection coefficients as strong as 12% accumulating without strong constraints on genetic background. In vivo competitive assays showed that one of the second steps (focA) exhibited positive epistasis with the first, while another (dcuB) exhibited negative epistasis. The data shows that strong effect adaptive mutations continuously recur in gut commensal bacterial species.

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Section: Discussionmentioning

confidence: 99%

A Mutational Hotspot and Strong Selection Contribute to the Order of Mutations Selected for during Escherichia coli Adaptation to the Gut

et al. 2016

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“…In particular, considerable uncertainty surrounds the relative importance of the availability of adaptive mutations, pleiotropy and epistasis in constraining adaptive paths (Stern 2011;Storz 2018). One fruitful approach to addressing this question has been to examine repeated bouts of adaptation in microbial systems subject to a common selective pressure and identical starting conditions (Jerison and Desai 2015). Unfortunately, such approaches still have limited utility in multicellular eukaryotes and likely don't reveal the full range of constraints operating in nature.…”

Section: Introductionmentioning

confidence: 99%

Adaptive substitutions underlying cardiac glycoside insensitivity in insects exhibit epistasis in vivo

Taverner

Yang

Barile

et al. 2019

Preprint

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Predicting how species will respond to selection pressures requires understanding the factors that constrain their evolution. We use genome engineering of Drosophila to investigate constraints on the repeated evolution of unrelated herbivorous insects to toxic cardiac glycosides, which primarily occurs via a small subset of possible functionally-relevant substitutions to Na + ,K + -ATPase. Surprisingly, we find that frequently observed adaptive substitutions at two sites, 111 and 122, are lethal when homozygous and adult heterozygotes exhibit dominant neural dysfunction. We identify a phylogenetically correlated substitution, A119S, that partially ameliorates the deleterious effects of substitutions at 111 and 122. Despite contributing little to cardiac glycoside-insensitivity in vitro, A119S, like substitutions at 111 and 122, substantially increases adult survivorship upon cardiac glycoside exposure. Our results demonstrate the importance of epistasis in constraining adaptive paths. Moreover, by revealing distinct effects of substitutions in vitro and in vivo, our results underscore the importance of evaluating the fitness of adaptive substitutions and their interactions in whole organisms.

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“…Previous studies of pathogens [12], laboratory evolution experiments [13], and some environmental communities [14][15][16][17] have shown that microbial evolutionary dynamics are often dominated by rapid adaptation, with new variants accumulating within months or years [7,14,[18][19][20][21][22][23][24][25]. However, it is not clear how this existing picture of microbial evolution extends to a more complex and established ecosystem like the healthy gut microbiome.…”

Section: Introductionmentioning

confidence: 99%

Evolutionary dynamics of bacteria in the gut microbiome within and across hosts

Garud

Good

Hallatschek

et al. 2017

Preprint

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The structure and function of the gut microbiome are shaped by a combination of ecological and evolutionary forces. While the ecological dynamics of the community have been extensively studied, much less is known about how strains of gut bacteria evolve over time. Here we show that with a model-based analysis of existing shotgun metagenomic data, we can gain new insights into the evolutionary dynamics of gut bacteria within and across hosts. We find that long-term evolution across hosts is consistent with quasi-sexual evolution and purifying selection, with relatively weak geographic structure in many prevalent species. However, our quantitative approach also reveals new between-host genealogical signatures that cannot be explained by standard population genetic models. By comparing samples from the same host over ∼6 month timescales, we find that within-host differences rarely arise from the invasion of strains as distantly related as those in other hosts. Instead, we more commonly observe a small number of evolutionary changes in resident strains, in which nucleotide variants or gene gains or losses rapidly sweep to high frequency within a host. By comparing the signatures of these mutations with the typical between-host differences, we find evidence that many sweeps are driven by introgression from existing species or strains, rather than by de novo mutations. These data suggest that bacteria in the microbiome can evolve on human relevant timescales, and highlight the feedback between these short-term changes and the longer-term evolution across hosts. INTRODUCTIONThe gut microbiome is a complex ecosystem comprised of a diverse array of microbial organisms. The abundances of different species and strains can vary dramatically based on diet (1), host-species (2), and the identities of other co-colonizing taxa (3). These rapid shifts in community composition suggest that individual gut microbes may be adapted to specific environmental conditions, with strong selection pressures between competing species or strains. Yet while these ecological responses have been extensively studied, much less is known about the evolutionary forces that operate within populations of gut bacteria, both inside individual hosts, and across the larger host-associated population. This makes it difficult to predict how rapidly strains of gut microbes will evolve new ecological preferences and traits when faced with environmental challenges, and how the genetic fingerprint of the community will change as a result.The answers to these questions depend on two different types of information. At a mechanistic level, we must understand the functional traits that are under selection in the gut, and the range of genetic mutations that can alter these traits. Although it can be challenging to measure such selection pressures in vivo, comparative genomics (4, 5), experiments in model organisms (6, 7), and high-throughput screens (8, 9) are starting to provide valuable information about the functional traits required to thrive in the gut environm...

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Genomic investigations of evolutionary dynamics and epistasis in microbial evolution experiments

Cited by 62 publications

References 91 publications

A Mutational Hotspot and Strong Selection Contribute to the Order of Mutations Selected for during Escherichia coli Adaptation to the Gut

A Mutational Hotspot and Strong Selection Contribute to the Order of Mutations Selected for during Escherichia coli Adaptation to the Gut

Adaptive substitutions underlying cardiac glycoside insensitivity in insects exhibit epistasis in vivo

Evolutionary dynamics of bacteria in the gut microbiome within and across hosts

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