Broad Conditions Favor the Evolution of Phase-Variable Loci

ABSTRACT Simple sequence repeat (SSR) tracts produce stochastic on-off switching, or phase variation, in the expression of a panoply of surface molecules in many bacterial commensals and pathogens. A change to the number of repeats in a tract may alter the phase of the translational reading frame, w...

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Autores principales:	M. E. Palmer, M. Lipsitch, E. R. Moxon, C. D. Bayliss
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2013
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/426dafdea48049ef863170ef385c0f61
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spelling	oai:doaj.org-article:426dafdea48049ef863170ef385c0f612021-11-15T15:40:21ZBroad Conditions Favor the Evolution of Phase-Variable Loci10.1128/mBio.00430-122150-7511https://doaj.org/article/426dafdea48049ef863170ef385c0f612013-03-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00430-12https://doaj.org/toc/2150-7511ABSTRACT Simple sequence repeat (SSR) tracts produce stochastic on-off switching, or phase variation, in the expression of a panoply of surface molecules in many bacterial commensals and pathogens. A change to the number of repeats in a tract may alter the phase of the translational reading frame, which toggles the on-off state of the switch. Here, we construct an in silico SSR locus with mutational dynamics calibrated to those of the Haemophilus influenzae mod locus. We simulate its evolution in a regimen of two alternating environments, simultaneously varying the selection coefficient, s, and the epoch length, T. Some recent work in a simpler (two-locus) model suggested that stochastic switching in a regimen of two alternating environments may be evolutionarily favored only if the selection coefficients in the two environments are nearly equal (“symmetric”) or selection is very strong. This finding was puzzling, as it greatly restricted the conditions under which stochastic switching might evolve. Instead, we find agreement with other recent theoretical work, observing selective utility for stochastic switching if the product sT is large enough for the favored state to nearly fix in both environments. Symmetry is required neither in s nor in sT. Because we simulate finite populations and use a detailed model of the SSR locus, we are also able to examine the impact of population size and of several SSR locus parameters. Our results indicate that conditions favoring evolution and maintenance of SSR loci in bacteria are quite broad. IMPORTANCE Bacteria experience frequent changes of environment during the infection cycle. One means to rapidly adapt is stochastic switching: a bacterial lineage will stochastically produce a variety of genotypes, so that some descendants will survive if the environment changes. Stochastic switching mediated by simple sequence repeat (SSR) loci is widespread among bacterial commensals and pathogens and influences critical interactions with host surfaces or immune effectors, thereby affecting host persistence, transmission, and virulence. Here, we use the most detailed in silico model of an SSR locus to date, with its phase variation calibrated to match the mod locus of Haemophilus influenzae. The type III restriction-modification system encoded by mod participates in the regulation of multiple other genes; thus, SSR-mediated phase variation of mod has far-reaching cis-regulatory effects. This coupling of phase-variable switching to complex phenotypic effects has been described as the “phasevarion” and is central to understanding the infection cycle of bacterial commensals and pathogens.M. E. PalmerM. LipsitchE. R. MoxonC. D. BaylissAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 4, Iss 1 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 M. E. Palmer M. Lipsitch E. R. Moxon C. D. Bayliss Broad Conditions Favor the Evolution of Phase-Variable Loci
description	ABSTRACT Simple sequence repeat (SSR) tracts produce stochastic on-off switching, or phase variation, in the expression of a panoply of surface molecules in many bacterial commensals and pathogens. A change to the number of repeats in a tract may alter the phase of the translational reading frame, which toggles the on-off state of the switch. Here, we construct an in silico SSR locus with mutational dynamics calibrated to those of the Haemophilus influenzae mod locus. We simulate its evolution in a regimen of two alternating environments, simultaneously varying the selection coefficient, s, and the epoch length, T. Some recent work in a simpler (two-locus) model suggested that stochastic switching in a regimen of two alternating environments may be evolutionarily favored only if the selection coefficients in the two environments are nearly equal (“symmetric”) or selection is very strong. This finding was puzzling, as it greatly restricted the conditions under which stochastic switching might evolve. Instead, we find agreement with other recent theoretical work, observing selective utility for stochastic switching if the product sT is large enough for the favored state to nearly fix in both environments. Symmetry is required neither in s nor in sT. Because we simulate finite populations and use a detailed model of the SSR locus, we are also able to examine the impact of population size and of several SSR locus parameters. Our results indicate that conditions favoring evolution and maintenance of SSR loci in bacteria are quite broad. IMPORTANCE Bacteria experience frequent changes of environment during the infection cycle. One means to rapidly adapt is stochastic switching: a bacterial lineage will stochastically produce a variety of genotypes, so that some descendants will survive if the environment changes. Stochastic switching mediated by simple sequence repeat (SSR) loci is widespread among bacterial commensals and pathogens and influences critical interactions with host surfaces or immune effectors, thereby affecting host persistence, transmission, and virulence. Here, we use the most detailed in silico model of an SSR locus to date, with its phase variation calibrated to match the mod locus of Haemophilus influenzae. The type III restriction-modification system encoded by mod participates in the regulation of multiple other genes; thus, SSR-mediated phase variation of mod has far-reaching cis-regulatory effects. This coupling of phase-variable switching to complex phenotypic effects has been described as the “phasevarion” and is central to understanding the infection cycle of bacterial commensals and pathogens.
format	article
author	M. E. Palmer M. Lipsitch E. R. Moxon C. D. Bayliss
author_facet	M. E. Palmer M. Lipsitch E. R. Moxon C. D. Bayliss
author_sort	M. E. Palmer
title	Broad Conditions Favor the Evolution of Phase-Variable Loci
title_short	Broad Conditions Favor the Evolution of Phase-Variable Loci
title_full	Broad Conditions Favor the Evolution of Phase-Variable Loci
title_fullStr	Broad Conditions Favor the Evolution of Phase-Variable Loci
title_full_unstemmed	Broad Conditions Favor the Evolution of Phase-Variable Loci
title_sort	broad conditions favor the evolution of phase-variable loci
publisher	American Society for Microbiology
publishDate	2013
url	https://doaj.org/article/426dafdea48049ef863170ef385c0f61
work_keys_str_mv	AT mepalmer broadconditionsfavortheevolutionofphasevariableloci AT mlipsitch broadconditionsfavortheevolutionofphasevariableloci AT ermoxon broadconditionsfavortheevolutionofphasevariableloci AT cdbayliss broadconditionsfavortheevolutionofphasevariableloci
_version_	1718427760826777600

Broad Conditions Favor the Evolution of Phase-Variable Loci

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