Nonselective Bottlenecks Control the Divergence and Diversification of Phase-Variable Bacterial Populations

Phase variation occurs in many pathogenic and commensal bacteria and is a major generator of genetic variability. A putative advantage of phase variation is to counter reductions in variability imposed by nonselective bottlenecks during transmission. Genomes of Campylobacter jejuni, a widespread food-borne pathogen, contain multiple phase-variable loci whose rapid, stochastic variation is generated by hypermutable simple sequence repeat tracts. These loci can occupy a vast number of combinatorial expression states (phasotypes) enabling populations to rapidly access phenotypic diversity. The imposition of nonselective bottlenecks can perturb the relative frequencies of phasotypes, changing both within-population diversity and divergence from the initial population. Using both in vitro testing of C. jejuni populations and a simple stochastic simulation of phasotype change, we observed that single-cell bottlenecks produce output populations of low diversity but with bimodal patterns of either high or low divergence. Conversely, large bottlenecks allow divergence only by accumulation of diversity, while interpolation between these extremes is observed in intermediary bottlenecks. These patterns are sensitive to the genetic diversity of initial populations but stable over a range of mutation rates and number of loci. The qualitative similarities of experimental and in silico modeling indicate that the observed patterns are robust and applicable to other systems where localized hypermutation is a defining feature. We conclude that while phase variation will maintain bacterial population diversity in the face of intermediate bottlenecks, narrow transmission-associated bottlenecks could produce host-to-host variation in bacterial phenotypes and hence stochastic variation in colonization and disease outcomes

Data from: Nonselective bottlenecks control the divergence and diversification of phase-variable bacterial populations

Phase variation occurs in many pathogenic and commensal bacteria and is a major generator of genetic variability. A putative advantage of phase variation is to counter reductions in variability imposed by nonselective bottlenecks during transmission. Genomes of Campylobacter jejuni, a widespread food-borne pathogen, contain multiple phase-variable loci whose rapid, stochastic variation is generated by hypermutable simple sequence repeat tracts. These loci can occupy a vast number of combinatorial expression states (phasotypes) enabling populations to rapidly access phenotypic diversity. The imposition of nonselective bottlenecks can perturb the relative frequencies of phasotypes, changing both within-population diversity and divergence from the initial population. Using both in vitro testing of C. jejuni populations and a simple stochastic simulation of phasotype change, we observed that single-cell bottlenecks produce output populations of low diversity but with bimodal patterns of either high or low divergence. Conversely, large bottlenecks allow divergence only by accumulation of diversity, while interpolation between these extremes is observed in intermediary bottlenecks. These patterns are sensitive to the genetic diversity of initial populations but stable over a range of mutation rates and number of loci. The qualitative similarities of experimental and in silico modeling indicate that the observed patterns are robust and applicable to other systems where localized hypermutation is a defining feature. We conclude that while phase variation will maintain bacterial population diversity in the face of intermediate bottlenecks, narrow transmission-associated bottlenecks could produce host-to-host variation in bacterial phenotypes and hence stochastic variation in colonization and disease outcomes

ExperimentalData

This folder contains the experimental data on bottlenecks and phase variation

Scripts_for_Figure_Preparation

This folder contains the scripts used for preparation of the figures in the mBio paper

Simulator_Output_Files

This folder contains the outputs from the simulator on bottlenecks and phase variation

Aidley_Bayliss_Archive_Map

Map of archive. This archive contains the scripts and data files contained within an mBio paper with first author Jack Aidley and last author Chris Bayliss. The scripts are for modelling the effect of non-selective bottlenecks on phase variable genes of Campylobacter jejuni. The data files contains the outputs of the scripts and related experimental data

Bottleneck Simulator

This folder contains the program files for the bottleneck simulator and a readme file that describes how the program works

Erratum for Aidley et al., "Nonselective Bottlenecks Control the Divergence and Diversification of Phase-Variable Bacterial Populations".

Volume 8, no. 2, e02311-16, 2017, https://doi.org/10.1128/mBio.02311-16. The byline and affiliation line of our article should appear as shown above. The following should also be added to the end of Acknowledgments: “M.A.J. was supported by the BBSRC (grant BBI02542).