The Experts below are selected from a list of 327 Experts worldwide ranked by ideXlab platform
Nicholas J. Croucher - One of the best experts on this subject based on the ideXlab platform.
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Negative Frequency-dependent selection and asymmetrical transformation stabilise multi-strain bacterial population structures
The ISME Journal, 2021Co-Authors: Gabrielle L. Harrow, Jukka Corander, John A. Lees, William P. Hanage, Marc Lipsitch, Caroline Colijn, Nicholas J. CroucherAbstract:Streptococcus pneumoniae can be divided into many strains, each a distinct set of isolates sharing similar core and accessory genomes, which co-circulate within the same hosts. Previous analyses suggested the short-term vaccine-associated dynamics of S. pneumoniae strains may be mediated through multi-locus Negative Frequency-dependent selection (NFDS), which maintains accessory loci at equilibrium frequencies. Long-term simulations demonstrated NFDS stabilised clonally-evolving multi-strain populations through preventing the loss of variation through drift, based on polymorphism frequencies, pairwise genetic distances and phylogenies. However, allowing symmetrical recombination between isolates evolving under multi-locus NFDS generated unstructured populations of diverse genotypes. Replication of the observed data improved when multi-locus NFDS was combined with recombination that was instead asymmetrical, favouring deletion of accessory loci over insertion. This combination separated populations into strains through outbreeding depression, resulting from recombinants with reduced accessory genomes having lower fitness than their parental genotypes. Although simplistic modelling of recombination likely limited these simulations’ ability to maintain some properties of genomic data as accurately as those lacking recombination, the combination of asymmetrical recombination and multi-locus NFDS could restore multi-strain population structures from randomised initial populations. As many bacteria inhibit insertions into their chromosomes, this combination may commonly underlie the co-existence of strains within a niche.
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Negative Frequency-dependent selection and asymmetrical transformation stabilise multi-strain bacterial population structures
2020Co-Authors: Gabrielle L. Harrow, Jukka Corander, John A. Lees, William P. Hanage, Marc Lipsitch, Caroline Colijn, Nicholas J. CroucherAbstract:Streptococcus pneumoniae can be split into multiple strains, each with a characteristic combination of core and accessory genome variation, able to co-circulate and compete within the same hosts. Previous analyses of epidemiological datasets suggested the short-term vaccine-associated dynamics of S. pneumoniae strains may be mediated through multi-locus Negative Frequency-dependent selection (NFDS), acting to maintain accessory loci at equilibrium frequencies. To test whether this model could explain how such multi-strain populations were generated, it was modified to incorporate recombination. The outputs of simulations featuring symmetrical recombination were compared with genomic data on locus frequencies and distributions between genotypes, pairwise genetic distances and tree shape. These demonstrated NFDS prevented the loss of variation through neutral drift, but generated unstructured populations of diverse isolates. Making recombination asymmetrical, favouring deletion of accessory loci over insertion, alongside multi-locus NFDS significantly improved the fit to genomic data. In a population at equilibrium, structuring into multiple strains was stable due to outbreeding depression, resulting from recombinants with reduced accessory genomes having lower fitness than their parental genotypes. As many bacteria inhibit the integration of insertions into their chromosomes, this combination of asymmetrical recombination and multi-locus NFDS may underlie the co-existence of strains within a single ecological niche.
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Diversification of Colonization Factors in a Multidrug-Resistant Escherichia coli Lineage Evolving under Negative Frequency-Dependent Selection.
mBio, 2019Co-Authors: Alan Mcnally, Teemu Kallonen, Christopher Connor, Khalil Abudahab, David M. Aanensen, Carolyne Horner, Sharon J. Peacock, Julian Parkhill, Nicholas J. Croucher, Jukka CoranderAbstract:ABSTRACT Escherichia coli is a major cause of bloodstream and urinary tract infections globally. The wide dissemination of multidrug-resistant (MDR) strains of extraintestinal pathogenic E. coli (ExPEC) poses a rapidly increasing public health burden due to narrowed treatment options and increased risk of failure to clear an infection. Here, we present a detailed population genomic analysis of the ExPEC ST131 clone, in which we seek explanations for its success as an emerging pathogenic strain beyond the acquisition of antimicrobial resistance (AMR) genes. We show evidence for evolution toward separate ecological niches for the main clades of ST131 and differential evolution of anaerobic metabolism, key colonization, and virulence factors. We further demonstrate that Negative Frequency-dependent selection acting across accessory loci is a major mechanism that has shaped the population evolution of this pathogen. IMPORTANCE Infections with multidrug-resistant (MDR) strains of Escherichia coli are a significant global public health concern. To combat these pathogens, we need a deeper understanding of how they evolved from their background populations. By understanding the processes that underpin their emergence, we can design new strategies to limit evolution of new clones and combat existing clones. By combining population genomics with modelling approaches, we show that dominant MDR clones of E. coli are under the influence of Negative Frequency-dependent selection, preventing them from rising to fixation in a population. Furthermore, we show that this selection acts on genes involved in anaerobic metabolism, suggesting that this key trait, and the ability to colonize human intestinal tracts, is a key step in the evolution of MDR clones of E. coli.
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Signatures of Negative Frequency dependent selection in colonisation factors and the evolution of a multi-drug resistant lineage of Escherichia coli
2018Co-Authors: Alan Mcnally, Teemu Kallonen, Christopher Connor, Khalil Abudahab, David M. Aanensen, Carolyne Horner, Sharon J. Peacock, Julian Parkhill, Nicholas J. Croucher, Jukka CoranderAbstract:Escherichia coli is a major cause of bloodstream and urinary tract infections globally. The wide dissemination of multi-drug resistant (MDR) strains of extra-intestinal pathogenic E. coli (ExPEC) pose a rapidly increasing public health burden due to narrowed treatment options and increased risk of failure to clear an infection. Here, we present a detailed population genomic analysis of the ExPEC ST131 clone, in which we seek explanations for its success as an emerging pathogenic strain beyond the acquisition of antimicrobial resistance (AMR) genes. We show evidence for a stepwise evolution towards separate ecological niches for the main clades of ST131 and differential evolution of anaerobic metabolism, key colonisation and virulence factors. We further demonstrate that Negative Frequency-dependent selection acting on these loci is a major mechanism that has shaped the population evolution of this pathogen.
Jeff Gore - One of the best experts on this subject based on the ideXlab platform.
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Negative Frequency‐dependent interactions can underlie phenotypic heterogeneity in a clonal microbial population
Molecular Systems Biology, 2016Co-Authors: David Healey, Kevin Axelrod, Jeff GoreAbstract:Genetically identical cells in microbial populations often exhibit a remarkable degree of phenotypic heterogeneity even in homogenous environments. Such heterogeneity is commonly thought to represent a bet-hedging strategy against environmental uncertainty. However, evolutionary game theory predicts that phenotypic heterogeneity may also be a response to Negative Frequency-dependent interactions that favor rare phenotypes over common ones. Here we provide experimental evidence for this alternative explanation in the context of the well-studied yeast GAL network. In an environment containing the two sugars glucose and galactose, the yeast GAL network displays stochastic bimodal activation. We show that in this mixed sugar environment, GAL-ON and GAL-OFF phenotypes can each invade the opposite phenotype when rare and that there exists a resulting stable mix of phenotypes. Consistent with theoretical predictions, the resulting stable mix of phenotypes is not necessarily optimal for population growth. We find that the wild-type mixed strategist GAL network can invade populations of both pure strategists while remaining uninvasible by either. Lastly, using laboratory evolution we show that this mixed resource environment can directly drive the de novo evolution of clonal phenotypic heterogeneity from a pure strategist population. Taken together, our results provide experimental evidence that Negative Frequency-dependent interactions can underlie the phenotypic heterogeneity found in clonal microbial populations.
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Negative Frequency dependent interactions can underlie phenotypic heterogeneity in a clonal microbial population
Molecular Systems Biology, 2016Co-Authors: David Healey, Kevin Axelrod, Jeff GoreAbstract:Genetically identical cells in microbial populations often exhibit a remarkable degree of phenotypic heterogeneity even in homogenous environments. Such heterogeneity is commonly thought to represent a bet-hedging strategy against environmental uncertainty. However, evolutionary game theory predicts that phenotypic heterogeneity may also be a response to Negative Frequency-dependent interactions that favor rare phenotypes over common ones. Here we provide experimental evidence for this alternative explanation in the context of the well-studied yeast GAL network. In an environment containing the two sugars glucose and galactose, the yeast GAL network displays stochastic bimodal activation. We show that in this mixed sugar environment, GAL-ON and GAL-OFF phenotypes can each invade the opposite phenotype when rare and that there exists a resulting stable mix of phenotypes. Consistent with theoretical predictions, the resulting stable mix of phenotypes is not necessarily optimal for population growth. We find that the wild-type mixed strategist GAL network can invade populations of both pure strategists while remaining uninvasible by either. Lastly, using laboratory evolution we show that this mixed resource environment can directly drive the de novo evolution of clonal phenotypic heterogeneity from a pure strategist population. Taken together, our results provide experimental evidence that Negative Frequency-dependent interactions can underlie the phenotypic heterogeneity found in clonal microbial populations.
Stéphanie Mariette - One of the best experts on this subject based on the ideXlab platform.
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Microevolution of s-allele frequencies in wild cherry populations: respective impacts of Negative Frequency dependent selection and genetic drift
Evolution - International Journal of Organic Evolution, 2012Co-Authors: Solenn Stoeckel, Sylvie Oddou-muratorio, Brigitte Musch, E. Klein, Stéphanie MarietteAbstract:Negative Frequency dependent selection (NFDS) is supposed to be the main force controlling allele evolution at the gametophytic self-incompatibility locus (S-locus) in strictly outcrossing species. Genetic drift also influences S-allele evolution. In perennial sessile organisms, evolution of allelic frequencies over two generations is mainly shaped by individual fecundities and spatial processes. Using wild cherry populations between two successive generations, we tested whether S-alleles evolved following NFDS qualitative and quantitative predictions. We showed that allelic variation was Negatively correlated with parental allelic Frequency as expected under NFDS. However, NFDS predictions in finite population failed to predict more than half S-allele quantitative evolution. We developed a spatially explicit mating model that included the S-locus. We studied the effects of self-incompatibility and local drift within populations due to pollen dispersal in spatially distributed individuals, and variation in male fecundity on male mating success and allelic Frequency evolution. Male mating success was Negatively related to male allelic Frequency as expected under NFDS. Spatial genetic structure combined with self-incompatibility resulted in higher effective pollen dispersal. Limited pollen dispersal in structured distributions of individuals and genotypes and unequal pollen production significantly contributed to S-allele Frequency evolution by creating local drift effects strong enough to counteract the NFDS effect on some alleles.
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MICROEVOLUTION OF S‐ALLELE FREQUENCIES IN WILD CHERRY POPULATIONS: RESPECTIVE IMPACTS OF Negative Frequency DEPENDENT SELECTION AND GENETIC DRIFT
Evolution; international journal of organic evolution, 2011Co-Authors: Solenn Stoeckel, Etienne K. Klein, Sylvie Oddou-muratorio, Brigitte Musch, Stéphanie MarietteAbstract:Negative Frequency dependent selection (NFDS) is supposed to be the main force controlling allele evolution at the gametophytic self-incompatibility locus (S-locus) in strictly outcrossing species. Genetic drift also influences S-allele evolution. In perennial sessile organisms, evolution of allelic frequencies over two generations is mainly shaped by individual fecundities and spatial processes. Using wild cherry populations between two successive generations, we tested whether S-alleles evolved following NFDS qualitative and quantitative predictions. We showed that allelic variation was Negatively correlated with parental allelic Frequency as expected under NFDS. However, NFDS predictions in finite population failed to predict more than half S-allele quantitative evolution. We developed a spatially explicit mating model that included the S-locus. We studied the effects of self-incompatibility and local drift within populations due to pollen dispersal in spatially distributed individuals, and variation in male fecundity on male mating success and allelic Frequency evolution. Male mating success was Negatively related to male allelic Frequency as expected under NFDS. Spatial genetic structure combined with self-incompatibility resulted in higher effective pollen dispersal. Limited pollen dispersal in structured distributions of individuals and genotypes and unequal pollen production significantly contributed to S-allele Frequency evolution by creating local drift effects strong enough to counteract the NFDS effect on some alleles.
Jukka Corander - One of the best experts on this subject based on the ideXlab platform.
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Negative Frequency-dependent selection and asymmetrical transformation stabilise multi-strain bacterial population structures
The ISME Journal, 2021Co-Authors: Gabrielle L. Harrow, Jukka Corander, John A. Lees, William P. Hanage, Marc Lipsitch, Caroline Colijn, Nicholas J. CroucherAbstract:Streptococcus pneumoniae can be divided into many strains, each a distinct set of isolates sharing similar core and accessory genomes, which co-circulate within the same hosts. Previous analyses suggested the short-term vaccine-associated dynamics of S. pneumoniae strains may be mediated through multi-locus Negative Frequency-dependent selection (NFDS), which maintains accessory loci at equilibrium frequencies. Long-term simulations demonstrated NFDS stabilised clonally-evolving multi-strain populations through preventing the loss of variation through drift, based on polymorphism frequencies, pairwise genetic distances and phylogenies. However, allowing symmetrical recombination between isolates evolving under multi-locus NFDS generated unstructured populations of diverse genotypes. Replication of the observed data improved when multi-locus NFDS was combined with recombination that was instead asymmetrical, favouring deletion of accessory loci over insertion. This combination separated populations into strains through outbreeding depression, resulting from recombinants with reduced accessory genomes having lower fitness than their parental genotypes. Although simplistic modelling of recombination likely limited these simulations’ ability to maintain some properties of genomic data as accurately as those lacking recombination, the combination of asymmetrical recombination and multi-locus NFDS could restore multi-strain population structures from randomised initial populations. As many bacteria inhibit insertions into their chromosomes, this combination may commonly underlie the co-existence of strains within a niche.
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Negative Frequency-dependent selection and asymmetrical transformation stabilise multi-strain bacterial population structures
2020Co-Authors: Gabrielle L. Harrow, Jukka Corander, John A. Lees, William P. Hanage, Marc Lipsitch, Caroline Colijn, Nicholas J. CroucherAbstract:Streptococcus pneumoniae can be split into multiple strains, each with a characteristic combination of core and accessory genome variation, able to co-circulate and compete within the same hosts. Previous analyses of epidemiological datasets suggested the short-term vaccine-associated dynamics of S. pneumoniae strains may be mediated through multi-locus Negative Frequency-dependent selection (NFDS), acting to maintain accessory loci at equilibrium frequencies. To test whether this model could explain how such multi-strain populations were generated, it was modified to incorporate recombination. The outputs of simulations featuring symmetrical recombination were compared with genomic data on locus frequencies and distributions between genotypes, pairwise genetic distances and tree shape. These demonstrated NFDS prevented the loss of variation through neutral drift, but generated unstructured populations of diverse isolates. Making recombination asymmetrical, favouring deletion of accessory loci over insertion, alongside multi-locus NFDS significantly improved the fit to genomic data. In a population at equilibrium, structuring into multiple strains was stable due to outbreeding depression, resulting from recombinants with reduced accessory genomes having lower fitness than their parental genotypes. As many bacteria inhibit the integration of insertions into their chromosomes, this combination of asymmetrical recombination and multi-locus NFDS may underlie the co-existence of strains within a single ecological niche.
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Diversification of Colonization Factors in a Multidrug-Resistant Escherichia coli Lineage Evolving under Negative Frequency-Dependent Selection.
mBio, 2019Co-Authors: Alan Mcnally, Teemu Kallonen, Christopher Connor, Khalil Abudahab, David M. Aanensen, Carolyne Horner, Sharon J. Peacock, Julian Parkhill, Nicholas J. Croucher, Jukka CoranderAbstract:ABSTRACT Escherichia coli is a major cause of bloodstream and urinary tract infections globally. The wide dissemination of multidrug-resistant (MDR) strains of extraintestinal pathogenic E. coli (ExPEC) poses a rapidly increasing public health burden due to narrowed treatment options and increased risk of failure to clear an infection. Here, we present a detailed population genomic analysis of the ExPEC ST131 clone, in which we seek explanations for its success as an emerging pathogenic strain beyond the acquisition of antimicrobial resistance (AMR) genes. We show evidence for evolution toward separate ecological niches for the main clades of ST131 and differential evolution of anaerobic metabolism, key colonization, and virulence factors. We further demonstrate that Negative Frequency-dependent selection acting across accessory loci is a major mechanism that has shaped the population evolution of this pathogen. IMPORTANCE Infections with multidrug-resistant (MDR) strains of Escherichia coli are a significant global public health concern. To combat these pathogens, we need a deeper understanding of how they evolved from their background populations. By understanding the processes that underpin their emergence, we can design new strategies to limit evolution of new clones and combat existing clones. By combining population genomics with modelling approaches, we show that dominant MDR clones of E. coli are under the influence of Negative Frequency-dependent selection, preventing them from rising to fixation in a population. Furthermore, we show that this selection acts on genes involved in anaerobic metabolism, suggesting that this key trait, and the ability to colonize human intestinal tracts, is a key step in the evolution of MDR clones of E. coli.
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Signatures of Negative Frequency dependent selection in colonisation factors and the evolution of a multi-drug resistant lineage of Escherichia coli
2018Co-Authors: Alan Mcnally, Teemu Kallonen, Christopher Connor, Khalil Abudahab, David M. Aanensen, Carolyne Horner, Sharon J. Peacock, Julian Parkhill, Nicholas J. Croucher, Jukka CoranderAbstract:Escherichia coli is a major cause of bloodstream and urinary tract infections globally. The wide dissemination of multi-drug resistant (MDR) strains of extra-intestinal pathogenic E. coli (ExPEC) pose a rapidly increasing public health burden due to narrowed treatment options and increased risk of failure to clear an infection. Here, we present a detailed population genomic analysis of the ExPEC ST131 clone, in which we seek explanations for its success as an emerging pathogenic strain beyond the acquisition of antimicrobial resistance (AMR) genes. We show evidence for a stepwise evolution towards separate ecological niches for the main clades of ST131 and differential evolution of anaerobic metabolism, key colonisation and virulence factors. We further demonstrate that Negative Frequency-dependent selection acting on these loci is a major mechanism that has shaped the population evolution of this pathogen.
Gabrielle L. Harrow - One of the best experts on this subject based on the ideXlab platform.
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Negative Frequency-dependent selection and asymmetrical transformation stabilise multi-strain bacterial population structures
The ISME Journal, 2021Co-Authors: Gabrielle L. Harrow, Jukka Corander, John A. Lees, William P. Hanage, Marc Lipsitch, Caroline Colijn, Nicholas J. CroucherAbstract:Streptococcus pneumoniae can be divided into many strains, each a distinct set of isolates sharing similar core and accessory genomes, which co-circulate within the same hosts. Previous analyses suggested the short-term vaccine-associated dynamics of S. pneumoniae strains may be mediated through multi-locus Negative Frequency-dependent selection (NFDS), which maintains accessory loci at equilibrium frequencies. Long-term simulations demonstrated NFDS stabilised clonally-evolving multi-strain populations through preventing the loss of variation through drift, based on polymorphism frequencies, pairwise genetic distances and phylogenies. However, allowing symmetrical recombination between isolates evolving under multi-locus NFDS generated unstructured populations of diverse genotypes. Replication of the observed data improved when multi-locus NFDS was combined with recombination that was instead asymmetrical, favouring deletion of accessory loci over insertion. This combination separated populations into strains through outbreeding depression, resulting from recombinants with reduced accessory genomes having lower fitness than their parental genotypes. Although simplistic modelling of recombination likely limited these simulations’ ability to maintain some properties of genomic data as accurately as those lacking recombination, the combination of asymmetrical recombination and multi-locus NFDS could restore multi-strain population structures from randomised initial populations. As many bacteria inhibit insertions into their chromosomes, this combination may commonly underlie the co-existence of strains within a niche.
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Negative Frequency-dependent selection and asymmetrical transformation stabilise multi-strain bacterial population structures
2020Co-Authors: Gabrielle L. Harrow, Jukka Corander, John A. Lees, William P. Hanage, Marc Lipsitch, Caroline Colijn, Nicholas J. CroucherAbstract:Streptococcus pneumoniae can be split into multiple strains, each with a characteristic combination of core and accessory genome variation, able to co-circulate and compete within the same hosts. Previous analyses of epidemiological datasets suggested the short-term vaccine-associated dynamics of S. pneumoniae strains may be mediated through multi-locus Negative Frequency-dependent selection (NFDS), acting to maintain accessory loci at equilibrium frequencies. To test whether this model could explain how such multi-strain populations were generated, it was modified to incorporate recombination. The outputs of simulations featuring symmetrical recombination were compared with genomic data on locus frequencies and distributions between genotypes, pairwise genetic distances and tree shape. These demonstrated NFDS prevented the loss of variation through neutral drift, but generated unstructured populations of diverse isolates. Making recombination asymmetrical, favouring deletion of accessory loci over insertion, alongside multi-locus NFDS significantly improved the fit to genomic data. In a population at equilibrium, structuring into multiple strains was stable due to outbreeding depression, resulting from recombinants with reduced accessory genomes having lower fitness than their parental genotypes. As many bacteria inhibit the integration of insertions into their chromosomes, this combination of asymmetrical recombination and multi-locus NFDS may underlie the co-existence of strains within a single ecological niche.
