The Symmetrical Wave Pattern of Base-Pair Substitution Rates across the <named-content content-type="genus-species">Escherichia coli</named-content> Chromosome Has Multiple Causes

ABSTRACT Mutation accumulation experiments followed by whole-genome sequencing have revealed that, for several bacterial species, the rate of base-pair substitutions (BPSs) is not constant across the chromosome but varies in a wave-like pattern that is symmetrical about the origin of replication. Th...

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Autores principales:	Brittany A. Niccum, Heewook Lee, Wazim MohammedIsmail, Haixu Tang, Patricia L. Foster
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	Escherichia coli mismatch repair mutation accumulation mutation rate nucleoid-associated proteins nucleoside triphosphate pools Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/cdc38ff6c16e4628ad3d167ba17abdb4
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spelling	oai:doaj.org-article:cdc38ff6c16e4628ad3d167ba17abdb42021-11-15T16:22:09ZThe Symmetrical Wave Pattern of Base-Pair Substitution Rates across the <named-content content-type="genus-species">Escherichia coli</named-content> Chromosome Has Multiple Causes10.1128/mBio.01226-192150-7511https://doaj.org/article/cdc38ff6c16e4628ad3d167ba17abdb42019-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01226-19https://doaj.org/toc/2150-7511ABSTRACT Mutation accumulation experiments followed by whole-genome sequencing have revealed that, for several bacterial species, the rate of base-pair substitutions (BPSs) is not constant across the chromosome but varies in a wave-like pattern that is symmetrical about the origin of replication. The experiments reported here demonstrated that, in Escherichia coli, several interacting factors determine the wave. The origin is a major driver of BPS rates. When it is relocated, the BPS rates in a 1,000-kb region surrounding the new origin reproduce the pattern that surrounds the normal origin. However, the pattern across distant regions of the chromosome is unaltered and thus must be determined by other factors. Increasing the deoxynucleoside triphosphate (dNTP) concentration shifts the wave pattern away from the origin, supporting the hypothesis that fluctuations in dNTP pools coincident with replication firing contribute to the variations in the mutation rate. The nucleoid binding proteins (HU and Fis) and the terminus organizing protein (MatP) are also major factors. These proteins alter the three-dimensional structure of the DNA, and results suggest that mutation rates increase when highly structured DNA is replicated. Biases in error correction by proofreading and mismatch repair, both of which may be responsive to dNTP concentrations and DNA structure, also are major determinants of the wave pattern. These factors should apply to most bacterial and, possibly, eukaryotic genomes and suggest that different areas of the genome evolve at different rates. IMPORTANCE It has been found in several species of bacteria that the rate at which single base pairs are mutated is not constant across the genome but varies in a wave-like pattern that is symmetrical about the origin of replication. Using Escherichia coli as our model system, we show that this pattern is the result of several interconnected factors. First, the timing and progression of replication are important in determining the wave pattern. Second, the three-dimensional structure of the DNA is also a factor, and the results suggest that mutation rates increase when highly structured DNA is replicated. Finally, biases in error correction, which may be responsive both to the progression of DNA synthesis and to DNA structure, are major determinants of the wave pattern. These factors should apply to most bacterial and, possibly, eukaryotic genomes and suggest that different areas of the genome evolve at different rates.Brittany A. NiccumHeewook LeeWazim MohammedIsmailHaixu TangPatricia L. FosterAmerican Society for MicrobiologyarticleEscherichia colimismatch repairmutation accumulationmutation ratenucleoid-associated proteinsnucleoside triphosphate poolsMicrobiologyQR1-502ENmBio, Vol 10, Iss 4 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Escherichia coli mismatch repair mutation accumulation mutation rate nucleoid-associated proteins nucleoside triphosphate pools Microbiology QR1-502
spellingShingle	Escherichia coli mismatch repair mutation accumulation mutation rate nucleoid-associated proteins nucleoside triphosphate pools Microbiology QR1-502 Brittany A. Niccum Heewook Lee Wazim MohammedIsmail Haixu Tang Patricia L. Foster The Symmetrical Wave Pattern of Base-Pair Substitution Rates across the <named-content content-type="genus-species">Escherichia coli</named-content> Chromosome Has Multiple Causes
description	ABSTRACT Mutation accumulation experiments followed by whole-genome sequencing have revealed that, for several bacterial species, the rate of base-pair substitutions (BPSs) is not constant across the chromosome but varies in a wave-like pattern that is symmetrical about the origin of replication. The experiments reported here demonstrated that, in Escherichia coli, several interacting factors determine the wave. The origin is a major driver of BPS rates. When it is relocated, the BPS rates in a 1,000-kb region surrounding the new origin reproduce the pattern that surrounds the normal origin. However, the pattern across distant regions of the chromosome is unaltered and thus must be determined by other factors. Increasing the deoxynucleoside triphosphate (dNTP) concentration shifts the wave pattern away from the origin, supporting the hypothesis that fluctuations in dNTP pools coincident with replication firing contribute to the variations in the mutation rate. The nucleoid binding proteins (HU and Fis) and the terminus organizing protein (MatP) are also major factors. These proteins alter the three-dimensional structure of the DNA, and results suggest that mutation rates increase when highly structured DNA is replicated. Biases in error correction by proofreading and mismatch repair, both of which may be responsive to dNTP concentrations and DNA structure, also are major determinants of the wave pattern. These factors should apply to most bacterial and, possibly, eukaryotic genomes and suggest that different areas of the genome evolve at different rates. IMPORTANCE It has been found in several species of bacteria that the rate at which single base pairs are mutated is not constant across the genome but varies in a wave-like pattern that is symmetrical about the origin of replication. Using Escherichia coli as our model system, we show that this pattern is the result of several interconnected factors. First, the timing and progression of replication are important in determining the wave pattern. Second, the three-dimensional structure of the DNA is also a factor, and the results suggest that mutation rates increase when highly structured DNA is replicated. Finally, biases in error correction, which may be responsive both to the progression of DNA synthesis and to DNA structure, are major determinants of the wave pattern. These factors should apply to most bacterial and, possibly, eukaryotic genomes and suggest that different areas of the genome evolve at different rates.
format	article
author	Brittany A. Niccum Heewook Lee Wazim MohammedIsmail Haixu Tang Patricia L. Foster
author_facet	Brittany A. Niccum Heewook Lee Wazim MohammedIsmail Haixu Tang Patricia L. Foster
author_sort	Brittany A. Niccum
title	The Symmetrical Wave Pattern of Base-Pair Substitution Rates across the <named-content content-type="genus-species">Escherichia coli</named-content> Chromosome Has Multiple Causes
title_short	The Symmetrical Wave Pattern of Base-Pair Substitution Rates across the <named-content content-type="genus-species">Escherichia coli</named-content> Chromosome Has Multiple Causes
title_full	The Symmetrical Wave Pattern of Base-Pair Substitution Rates across the <named-content content-type="genus-species">Escherichia coli</named-content> Chromosome Has Multiple Causes
title_fullStr	The Symmetrical Wave Pattern of Base-Pair Substitution Rates across the <named-content content-type="genus-species">Escherichia coli</named-content> Chromosome Has Multiple Causes
title_full_unstemmed	The Symmetrical Wave Pattern of Base-Pair Substitution Rates across the <named-content content-type="genus-species">Escherichia coli</named-content> Chromosome Has Multiple Causes
title_sort	symmetrical wave pattern of base-pair substitution rates across the <named-content content-type="genus-species">escherichia coli</named-content> chromosome has multiple causes
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/cdc38ff6c16e4628ad3d167ba17abdb4
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The Symmetrical Wave Pattern of Base-Pair Substitution Rates across the <named-content content-type="genus-species">Escherichia coli</named-content> Chromosome Has Multiple Causes

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