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 foo...

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Main Authors: Aidley, Jack B., Rajopadhye, Shweta, Akinyemi, Nwanekka, Lango-Scholey, Lea, Jones, Michael A., Bayliss, Christopher D.
Format: Article
Published: American Society for Microbiology 2017
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Online Access:https://eprints.nottingham.ac.uk/45520/
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author Aidley, Jack B.
Rajopadhye, Shweta
Akinyemi, Nwanekka
Lango-Scholey, Lea
Jones, Michael A.
Bayliss, Christopher D.
author_facet Aidley, Jack B.
Rajopadhye, Shweta
Akinyemi, Nwanekka
Lango-Scholey, Lea
Jones, Michael A.
Bayliss, Christopher D.
author_sort Aidley, Jack B.
building Nottingham Research Data Repository
collection Online Access
description 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.
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spelling nottingham-455202020-05-04T18:40:40Z https://eprints.nottingham.ac.uk/45520/ Nonselective bottlenecks control the divergence and diversification of phase-variable bacterial populations Aidley, Jack B. Rajopadhye, Shweta Akinyemi, Nwanekka Lango-Scholey, Lea Jones, Michael A. Bayliss, Christopher D. 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. American Society for Microbiology 2017-04-04 Article PeerReviewed Aidley, Jack B., Rajopadhye, Shweta, Akinyemi, Nwanekka, Lango-Scholey, Lea, Jones, Michael A. and Bayliss, Christopher D. (2017) Nonselective bottlenecks control the divergence and diversification of phase-variable bacterial populations. mBio, 8 (2). pp. 1-14. ISSN 2150-7511 Campylobacter Phase-variation http://mbio.asm.org/content/8/2/e02311-16 doi:10.1128/mBio.02311-16 doi:10.1128/mBio.02311-16
spellingShingle Campylobacter Phase-variation
Aidley, Jack B.
Rajopadhye, Shweta
Akinyemi, Nwanekka
Lango-Scholey, Lea
Jones, Michael A.
Bayliss, Christopher D.
Nonselective bottlenecks control the divergence and diversification of phase-variable bacterial populations
title Nonselective bottlenecks control the divergence and diversification of phase-variable bacterial populations
title_full Nonselective bottlenecks control the divergence and diversification of phase-variable bacterial populations
title_fullStr Nonselective bottlenecks control the divergence and diversification of phase-variable bacterial populations
title_full_unstemmed Nonselective bottlenecks control the divergence and diversification of phase-variable bacterial populations
title_short Nonselective bottlenecks control the divergence and diversification of phase-variable bacterial populations
title_sort nonselective bottlenecks control the divergence and diversification of phase-variable bacterial populations
topic Campylobacter Phase-variation
url https://eprints.nottingham.ac.uk/45520/
https://eprints.nottingham.ac.uk/45520/
https://eprints.nottingham.ac.uk/45520/