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Transcriptional Regulation Buffers Gene Dosage Effects on a Highly Expressed Operon in Salmonella

Highly expressed genes are commonly located close to the origin of replication of bacterial chromosomes (OriC). This location skew is thought to reflect selective advantages associated with gene dosage effects during the replication cycle. The expression of constitutively expressed genes can vary up...

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Autores principales: Garmendia, Eva, Brandis, Gerrit, Hughes, Diarmaid
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6134099/
https://www.ncbi.nlm.nih.gov/pubmed/30206172
http://dx.doi.org/10.1128/mBio.01446-18
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author Garmendia, Eva
Brandis, Gerrit
Hughes, Diarmaid
author_facet Garmendia, Eva
Brandis, Gerrit
Hughes, Diarmaid
author_sort Garmendia, Eva
collection PubMed
description Highly expressed genes are commonly located close to the origin of replication of bacterial chromosomes (OriC). This location skew is thought to reflect selective advantages associated with gene dosage effects during the replication cycle. The expression of constitutively expressed genes can vary up to fivefold based on chromosomal location, but it is not clear what level of variation would occur in naturally regulated operons. We tested the magnitude of the chromosome location effect using EF-Tu (tufA, tufB), an abundant protein whose cellular level correlates with, and limits, the maximum growth rate. We translocated the Salmonella tufB operon to four locations across the chromosome. The distance from OriC had only a small effect on growth rate, consistent with this operon having the natural ability to upregulate expression and compensate for reduced gene dosage. In contrast, when the total EF-Tu concentration was limiting for the growth rate (tufA deleted), we observed a strong gene dosage effect when tufB was located further from OriC. However, only a short period of experimental evolution was required before the bacteria adapted to this EF-Tu starvation situation by acquiring genetic changes that increased expression levels from the translocated tufB gene, restoring growth rates. Our findings demonstrate that, at least for the tufB operon, gene dosage is probably not the dominant force selecting for a chromosomal location close to OriC. We suggest that the colocation of highly expressed genes close to OriC might instead be selected because it enhances their coregulation during various growth states, with gene dosage being a secondary benefit.
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spelling pubmed-61340992018-09-17 Transcriptional Regulation Buffers Gene Dosage Effects on a Highly Expressed Operon in Salmonella Garmendia, Eva Brandis, Gerrit Hughes, Diarmaid mBio Research Article Highly expressed genes are commonly located close to the origin of replication of bacterial chromosomes (OriC). This location skew is thought to reflect selective advantages associated with gene dosage effects during the replication cycle. The expression of constitutively expressed genes can vary up to fivefold based on chromosomal location, but it is not clear what level of variation would occur in naturally regulated operons. We tested the magnitude of the chromosome location effect using EF-Tu (tufA, tufB), an abundant protein whose cellular level correlates with, and limits, the maximum growth rate. We translocated the Salmonella tufB operon to four locations across the chromosome. The distance from OriC had only a small effect on growth rate, consistent with this operon having the natural ability to upregulate expression and compensate for reduced gene dosage. In contrast, when the total EF-Tu concentration was limiting for the growth rate (tufA deleted), we observed a strong gene dosage effect when tufB was located further from OriC. However, only a short period of experimental evolution was required before the bacteria adapted to this EF-Tu starvation situation by acquiring genetic changes that increased expression levels from the translocated tufB gene, restoring growth rates. Our findings demonstrate that, at least for the tufB operon, gene dosage is probably not the dominant force selecting for a chromosomal location close to OriC. We suggest that the colocation of highly expressed genes close to OriC might instead be selected because it enhances their coregulation during various growth states, with gene dosage being a secondary benefit. American Society for Microbiology 2018-09-11 /pmc/articles/PMC6134099/ /pubmed/30206172 http://dx.doi.org/10.1128/mBio.01446-18 Text en Copyright © 2018 Garmendia et al. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Garmendia, Eva
Brandis, Gerrit
Hughes, Diarmaid
Transcriptional Regulation Buffers Gene Dosage Effects on a Highly Expressed Operon in Salmonella
title Transcriptional Regulation Buffers Gene Dosage Effects on a Highly Expressed Operon in Salmonella
title_full Transcriptional Regulation Buffers Gene Dosage Effects on a Highly Expressed Operon in Salmonella
title_fullStr Transcriptional Regulation Buffers Gene Dosage Effects on a Highly Expressed Operon in Salmonella
title_full_unstemmed Transcriptional Regulation Buffers Gene Dosage Effects on a Highly Expressed Operon in Salmonella
title_short Transcriptional Regulation Buffers Gene Dosage Effects on a Highly Expressed Operon in Salmonella
title_sort transcriptional regulation buffers gene dosage effects on a highly expressed operon in salmonella
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6134099/
https://www.ncbi.nlm.nih.gov/pubmed/30206172
http://dx.doi.org/10.1128/mBio.01446-18
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