Genomic Adaptations to the Loss of a Conserved Bacterial DNA Methyltransferase

ABSTRACT CcrM is an orphan DNA methyltransferase nearly universally conserved in a vast group of Alphaproteobacteria. In Caulobacter crescentus, it controls the expression of key genes involved in the regulation of the cell cycle and cell division. Here, we demonstrate, using an experimental evoluti...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Diego Gonzalez, Justine Collier
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2015
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/27200bf63f1746b28dc27b31d4b58592
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:27200bf63f1746b28dc27b31d4b58592
record_format	dspace
spelling	oai:doaj.org-article:27200bf63f1746b28dc27b31d4b585922021-11-15T15:41:26ZGenomic Adaptations to the Loss of a Conserved Bacterial DNA Methyltransferase10.1128/mBio.00952-152150-7511https://doaj.org/article/27200bf63f1746b28dc27b31d4b585922015-09-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00952-15https://doaj.org/toc/2150-7511ABSTRACT CcrM is an orphan DNA methyltransferase nearly universally conserved in a vast group of Alphaproteobacteria. In Caulobacter crescentus, it controls the expression of key genes involved in the regulation of the cell cycle and cell division. Here, we demonstrate, using an experimental evolution approach, that C. crescentus can significantly compensate, through easily accessible genetic changes like point mutations, the severe loss in fitness due to the absence of CcrM, quickly improving its growth rate and cell morphology in rich medium. By analyzing the compensatory mutations genome-wide in 12 clones sampled from independent ΔccrM populations evolved for ~300 generations, we demonstrated that each of the twelve clones carried at least one mutation that potentially stimulated ftsZ expression, suggesting that the low intracellular levels of FtsZ are the major burden of ΔccrM mutants. In addition, we demonstrate that the phosphoenolpyruvate-carbohydrate phosphotransfer system (PTS) actually modulates ftsZ and mipZ transcription, uncovering a previously unsuspected link between metabolic regulation and cell division in Alphaproteobacteria. We present evidence that point mutations found in genes encoding proteins of the PTS provide the strongest fitness advantage to ΔccrM cells cultivated in rich medium despite being disadvantageous in minimal medium. This environmental sign epistasis might prevent such mutations from getting fixed under changing natural conditions, adding a plausible explanation for the broad conservation of CcrM. IMPORTANCE In bacteria, DNA methylation has a variety of functions, including the control of DNA replication and/or gene expression. The cell cycle-regulated DNA methyltransferase CcrM modulates the transcription of many genes and is critical for fitness in Caulobacter crescentus. Here, we used an original experimental evolution approach to determine which of its many targets make CcrM so important physiologically. We show that populations lacking CcrM evolve quickly, accumulating an excess of mutations affecting, directly or indirectly, the expression of the ftsZ cell division gene. This finding suggests that the most critical function of CcrM in C. crescentus is to promote cell division by enhancing FtsZ intracellular levels. During this work, we also discovered an unexpected link between metabolic regulation and cell division that might extend to other Alphaproteobacteria.Diego GonzalezJustine CollierAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 6, Iss 4 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Diego Gonzalez Justine Collier Genomic Adaptations to the Loss of a Conserved Bacterial DNA Methyltransferase
description	ABSTRACT CcrM is an orphan DNA methyltransferase nearly universally conserved in a vast group of Alphaproteobacteria. In Caulobacter crescentus, it controls the expression of key genes involved in the regulation of the cell cycle and cell division. Here, we demonstrate, using an experimental evolution approach, that C. crescentus can significantly compensate, through easily accessible genetic changes like point mutations, the severe loss in fitness due to the absence of CcrM, quickly improving its growth rate and cell morphology in rich medium. By analyzing the compensatory mutations genome-wide in 12 clones sampled from independent ΔccrM populations evolved for ~300 generations, we demonstrated that each of the twelve clones carried at least one mutation that potentially stimulated ftsZ expression, suggesting that the low intracellular levels of FtsZ are the major burden of ΔccrM mutants. In addition, we demonstrate that the phosphoenolpyruvate-carbohydrate phosphotransfer system (PTS) actually modulates ftsZ and mipZ transcription, uncovering a previously unsuspected link between metabolic regulation and cell division in Alphaproteobacteria. We present evidence that point mutations found in genes encoding proteins of the PTS provide the strongest fitness advantage to ΔccrM cells cultivated in rich medium despite being disadvantageous in minimal medium. This environmental sign epistasis might prevent such mutations from getting fixed under changing natural conditions, adding a plausible explanation for the broad conservation of CcrM. IMPORTANCE In bacteria, DNA methylation has a variety of functions, including the control of DNA replication and/or gene expression. The cell cycle-regulated DNA methyltransferase CcrM modulates the transcription of many genes and is critical for fitness in Caulobacter crescentus. Here, we used an original experimental evolution approach to determine which of its many targets make CcrM so important physiologically. We show that populations lacking CcrM evolve quickly, accumulating an excess of mutations affecting, directly or indirectly, the expression of the ftsZ cell division gene. This finding suggests that the most critical function of CcrM in C. crescentus is to promote cell division by enhancing FtsZ intracellular levels. During this work, we also discovered an unexpected link between metabolic regulation and cell division that might extend to other Alphaproteobacteria.
format	article
author	Diego Gonzalez Justine Collier
author_facet	Diego Gonzalez Justine Collier
author_sort	Diego Gonzalez
title	Genomic Adaptations to the Loss of a Conserved Bacterial DNA Methyltransferase
title_short	Genomic Adaptations to the Loss of a Conserved Bacterial DNA Methyltransferase
title_full	Genomic Adaptations to the Loss of a Conserved Bacterial DNA Methyltransferase
title_fullStr	Genomic Adaptations to the Loss of a Conserved Bacterial DNA Methyltransferase
title_full_unstemmed	Genomic Adaptations to the Loss of a Conserved Bacterial DNA Methyltransferase
title_sort	genomic adaptations to the loss of a conserved bacterial dna methyltransferase
publisher	American Society for Microbiology
publishDate	2015
url	https://doaj.org/article/27200bf63f1746b28dc27b31d4b58592
work_keys_str_mv	AT diegogonzalez genomicadaptationstothelossofaconservedbacterialdnamethyltransferase AT justinecollier genomicadaptationstothelossofaconservedbacterialdnamethyltransferase
_version_	1718427694032486400

Genomic Adaptations to the Loss of a Conserved Bacterial DNA Methyltransferase

Ejemplares similares