Diversity in <italic toggle="yes">lac</italic> Operon Regulation among Diverse <named-content content-type="genus-species">Escherichia coli</named-content> Isolates Depends on the Broader Genetic Background but Is Not Explained by Genetic Relatedness

ABSTRACT Transcription of bacterial genes is controlled by the coordinated action of cis- and trans-acting regulators. The activity and mode of action of these regulators can reflect different requirements for gene products in different environments. A well-studied example is the regulatory function...

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Autores principales:	Kelly N. Phillips, Scott Widmann, Huei-Yi Lai, Jennifer Nguyen, J. Christian J. Ray, Gábor Balázsi, Tim F. Cooper
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	lac operon regulation Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/c82a47c04f42458d85f90c3cbb2b696e
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spelling	oai:doaj.org-article:c82a47c04f42458d85f90c3cbb2b696e2021-11-15T15:54:45ZDiversity in <italic toggle="yes">lac</italic> Operon Regulation among Diverse <named-content content-type="genus-species">Escherichia coli</named-content> Isolates Depends on the Broader Genetic Background but Is Not Explained by Genetic Relatedness10.1128/mBio.02232-192150-7511https://doaj.org/article/c82a47c04f42458d85f90c3cbb2b696e2019-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02232-19https://doaj.org/toc/2150-7511ABSTRACT Transcription of bacterial genes is controlled by the coordinated action of cis- and trans-acting regulators. The activity and mode of action of these regulators can reflect different requirements for gene products in different environments. A well-studied example is the regulatory function that integrates the environmental availability of glucose and lactose to control the Escherichia coli lac operon. Most studies of lac operon regulation have focused on a few closely related strains. To determine the range of natural variation in lac regulatory function, we introduced a reporter construct into 23 diverse E. coli strains and measured expression with combinations of inducer concentrations. We found a wide range of regulatory functions. Several functions were similar to the one observed in a reference lab strain, whereas others depended weakly on the presence of cAMP. Some characteristics of the regulatory function were explained by the genetic relatedness of strains, indicating that differences varied on relatively short time scales. The regulatory characteristics explained by genetic relatedness were among those that best predicted the initial growth of strains following transition to a lactose environment, suggesting a role for selection. Finally, we transferred the lac operon, with the lacI regulatory gene, from five natural isolate strains into a reference lab strain. The regulatory function of these hybrid strains revealed the effect of local and global regulatory elements in controlling expression. Together, this work demonstrates that regulatory functions can be varied within a species and that there is variation within a species to best match a function to particular environments. IMPORTANCE The lac operon of Escherichia coli is a classic model for studying gene regulation. This study has uncovered features such as the environmental input logic controlling gene expression, as well as gene expression bistability and hysteresis. Most lac operon studies have focused on a few lab strains, and it is not known how generally those findings apply to the diversity of E. coli strains. We examined the environmental dependence of lac gene regulation in 20 natural isolates of E. coli and found a wide range of regulatory responses. By transferring lac genes from natural isolate strains into a common reference strain, we found that regulation depends on both the lac genes themselves and on the broader genetic background, indicating potential for still-greater regulatory diversity following horizontal gene transfer. Our results reveal that there is substantial natural variation in the regulation of the lac operon and indicate that this variation can be ecologically meaningful.Kelly N. PhillipsScott WidmannHuei-Yi LaiJennifer NguyenJ. Christian J. RayGábor BalázsiTim F. CooperAmerican Society for Microbiologyarticlelac operon regulationMicrobiologyQR1-502ENmBio, Vol 10, Iss 6 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	lac operon regulation Microbiology QR1-502
spellingShingle	lac operon regulation Microbiology QR1-502 Kelly N. Phillips Scott Widmann Huei-Yi Lai Jennifer Nguyen J. Christian J. Ray Gábor Balázsi Tim F. Cooper Diversity in <italic toggle="yes">lac</italic> Operon Regulation among Diverse <named-content content-type="genus-species">Escherichia coli</named-content> Isolates Depends on the Broader Genetic Background but Is Not Explained by Genetic Relatedness
description	ABSTRACT Transcription of bacterial genes is controlled by the coordinated action of cis- and trans-acting regulators. The activity and mode of action of these regulators can reflect different requirements for gene products in different environments. A well-studied example is the regulatory function that integrates the environmental availability of glucose and lactose to control the Escherichia coli lac operon. Most studies of lac operon regulation have focused on a few closely related strains. To determine the range of natural variation in lac regulatory function, we introduced a reporter construct into 23 diverse E. coli strains and measured expression with combinations of inducer concentrations. We found a wide range of regulatory functions. Several functions were similar to the one observed in a reference lab strain, whereas others depended weakly on the presence of cAMP. Some characteristics of the regulatory function were explained by the genetic relatedness of strains, indicating that differences varied on relatively short time scales. The regulatory characteristics explained by genetic relatedness were among those that best predicted the initial growth of strains following transition to a lactose environment, suggesting a role for selection. Finally, we transferred the lac operon, with the lacI regulatory gene, from five natural isolate strains into a reference lab strain. The regulatory function of these hybrid strains revealed the effect of local and global regulatory elements in controlling expression. Together, this work demonstrates that regulatory functions can be varied within a species and that there is variation within a species to best match a function to particular environments. IMPORTANCE The lac operon of Escherichia coli is a classic model for studying gene regulation. This study has uncovered features such as the environmental input logic controlling gene expression, as well as gene expression bistability and hysteresis. Most lac operon studies have focused on a few lab strains, and it is not known how generally those findings apply to the diversity of E. coli strains. We examined the environmental dependence of lac gene regulation in 20 natural isolates of E. coli and found a wide range of regulatory responses. By transferring lac genes from natural isolate strains into a common reference strain, we found that regulation depends on both the lac genes themselves and on the broader genetic background, indicating potential for still-greater regulatory diversity following horizontal gene transfer. Our results reveal that there is substantial natural variation in the regulation of the lac operon and indicate that this variation can be ecologically meaningful.
format	article
author	Kelly N. Phillips Scott Widmann Huei-Yi Lai Jennifer Nguyen J. Christian J. Ray Gábor Balázsi Tim F. Cooper
author_facet	Kelly N. Phillips Scott Widmann Huei-Yi Lai Jennifer Nguyen J. Christian J. Ray Gábor Balázsi Tim F. Cooper
author_sort	Kelly N. Phillips
title	Diversity in <italic toggle="yes">lac</italic> Operon Regulation among Diverse <named-content content-type="genus-species">Escherichia coli</named-content> Isolates Depends on the Broader Genetic Background but Is Not Explained by Genetic Relatedness
title_short	Diversity in <italic toggle="yes">lac</italic> Operon Regulation among Diverse <named-content content-type="genus-species">Escherichia coli</named-content> Isolates Depends on the Broader Genetic Background but Is Not Explained by Genetic Relatedness
title_full	Diversity in <italic toggle="yes">lac</italic> Operon Regulation among Diverse <named-content content-type="genus-species">Escherichia coli</named-content> Isolates Depends on the Broader Genetic Background but Is Not Explained by Genetic Relatedness
title_fullStr	Diversity in <italic toggle="yes">lac</italic> Operon Regulation among Diverse <named-content content-type="genus-species">Escherichia coli</named-content> Isolates Depends on the Broader Genetic Background but Is Not Explained by Genetic Relatedness
title_full_unstemmed	Diversity in <italic toggle="yes">lac</italic> Operon Regulation among Diverse <named-content content-type="genus-species">Escherichia coli</named-content> Isolates Depends on the Broader Genetic Background but Is Not Explained by Genetic Relatedness
title_sort	diversity in <italic toggle="yes">lac</italic> operon regulation among diverse <named-content content-type="genus-species">escherichia coli</named-content> isolates depends on the broader genetic background but is not explained by genetic relatedness
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/c82a47c04f42458d85f90c3cbb2b696e
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Diversity in <italic toggle="yes">lac</italic> Operon Regulation among Diverse <named-content content-type="genus-species">Escherichia coli</named-content> Isolates Depends on the Broader Genetic Background but Is Not Explained by Genetic Relatedness

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