Periodic Variation of Mutation Rates in Bacterial Genomes Associated with Replication Timing

ABSTRACT The causes and consequences of spatiotemporal variation in mutation rates remain to be explored in nearly all organisms. Here we examine relationships between local mutation rates and replication timing in three bacterial species whose genomes have multiple chromosomes: Vibrio fischeri, Vib...

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Autores principales:	Marcus M. Dillon, Way Sung, Michael Lynch, Vaughn S. Cooper
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	Vibrio cholerae Vibrio fischeri genome organization mutation rate periodicity Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/2369bafe38c94f918a117fbaa84e404a
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spelling	oai:doaj.org-article:2369bafe38c94f918a117fbaa84e404a2021-11-15T16:00:15ZPeriodic Variation of Mutation Rates in Bacterial Genomes Associated with Replication Timing10.1128/mBio.01371-182150-7511https://doaj.org/article/2369bafe38c94f918a117fbaa84e404a2018-09-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01371-18https://doaj.org/toc/2150-7511ABSTRACT The causes and consequences of spatiotemporal variation in mutation rates remain to be explored in nearly all organisms. Here we examine relationships between local mutation rates and replication timing in three bacterial species whose genomes have multiple chromosomes: Vibrio fischeri, Vibrio cholerae, and Burkholderia cenocepacia. Following five mutation accumulation experiments with these bacteria conducted in the near absence of natural selection, the genomes of clones from each lineage were sequenced and analyzed to identify variation in mutation rates and spectra. In lineages lacking mismatch repair, base substitution mutation rates vary in a mirrored wave-like pattern on opposing replichores of the large chromosomes of V. fischeri and V. cholerae, where concurrently replicated regions experience similar base substitution mutation rates. The base substitution mutation rates on the small chromosome are less variable in both species but occur at similar rates to those in the concurrently replicated regions of the large chromosome. Neither nucleotide composition nor frequency of nucleotide motifs differed among regions experiencing high and low base substitution rates, which along with the inferred ~800-kb wave period suggests that the source of the periodicity is not sequence specific but rather a systematic process related to the cell cycle. These results support the notion that base substitution mutation rates are likely to vary systematically across many bacterial genomes, which exposes certain genes to elevated deleterious mutational load. IMPORTANCE That mutation rates vary within bacterial genomes is well known, but the detailed study of these biases has been made possible only recently with contemporary sequencing methods. We applied these methods to understand how bacterial genomes with multiple chromosomes, like those of Vibrio and Burkholderia, might experience heterogeneous mutation rates because of their unusual replication and the greater genetic diversity found on smaller chromosomes. This study captured thousands of mutations and revealed wave-like rate variation that is synchronized with replication timing and not explained by sequence context. The scale of this rate variation over hundreds of kilobases of DNA strongly suggests that a temporally regulated cellular process may generate wave-like variation in mutation risk. These findings add to our understanding of how mutation risk is distributed across bacterial and likely also eukaryotic genomes, owing to their highly conserved replication and repair machinery.Marcus M. DillonWay SungMichael LynchVaughn S. CooperAmerican Society for MicrobiologyarticleVibrio choleraeVibrio fischerigenome organizationmutation rateperiodicityMicrobiologyQR1-502ENmBio, Vol 9, Iss 4 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Vibrio cholerae Vibrio fischeri genome organization mutation rate periodicity Microbiology QR1-502
spellingShingle	Vibrio cholerae Vibrio fischeri genome organization mutation rate periodicity Microbiology QR1-502 Marcus M. Dillon Way Sung Michael Lynch Vaughn S. Cooper Periodic Variation of Mutation Rates in Bacterial Genomes Associated with Replication Timing
description	ABSTRACT The causes and consequences of spatiotemporal variation in mutation rates remain to be explored in nearly all organisms. Here we examine relationships between local mutation rates and replication timing in three bacterial species whose genomes have multiple chromosomes: Vibrio fischeri, Vibrio cholerae, and Burkholderia cenocepacia. Following five mutation accumulation experiments with these bacteria conducted in the near absence of natural selection, the genomes of clones from each lineage were sequenced and analyzed to identify variation in mutation rates and spectra. In lineages lacking mismatch repair, base substitution mutation rates vary in a mirrored wave-like pattern on opposing replichores of the large chromosomes of V. fischeri and V. cholerae, where concurrently replicated regions experience similar base substitution mutation rates. The base substitution mutation rates on the small chromosome are less variable in both species but occur at similar rates to those in the concurrently replicated regions of the large chromosome. Neither nucleotide composition nor frequency of nucleotide motifs differed among regions experiencing high and low base substitution rates, which along with the inferred ~800-kb wave period suggests that the source of the periodicity is not sequence specific but rather a systematic process related to the cell cycle. These results support the notion that base substitution mutation rates are likely to vary systematically across many bacterial genomes, which exposes certain genes to elevated deleterious mutational load. IMPORTANCE That mutation rates vary within bacterial genomes is well known, but the detailed study of these biases has been made possible only recently with contemporary sequencing methods. We applied these methods to understand how bacterial genomes with multiple chromosomes, like those of Vibrio and Burkholderia, might experience heterogeneous mutation rates because of their unusual replication and the greater genetic diversity found on smaller chromosomes. This study captured thousands of mutations and revealed wave-like rate variation that is synchronized with replication timing and not explained by sequence context. The scale of this rate variation over hundreds of kilobases of DNA strongly suggests that a temporally regulated cellular process may generate wave-like variation in mutation risk. These findings add to our understanding of how mutation risk is distributed across bacterial and likely also eukaryotic genomes, owing to their highly conserved replication and repair machinery.
format	article
author	Marcus M. Dillon Way Sung Michael Lynch Vaughn S. Cooper
author_facet	Marcus M. Dillon Way Sung Michael Lynch Vaughn S. Cooper
author_sort	Marcus M. Dillon
title	Periodic Variation of Mutation Rates in Bacterial Genomes Associated with Replication Timing
title_short	Periodic Variation of Mutation Rates in Bacterial Genomes Associated with Replication Timing
title_full	Periodic Variation of Mutation Rates in Bacterial Genomes Associated with Replication Timing
title_fullStr	Periodic Variation of Mutation Rates in Bacterial Genomes Associated with Replication Timing
title_full_unstemmed	Periodic Variation of Mutation Rates in Bacterial Genomes Associated with Replication Timing
title_sort	periodic variation of mutation rates in bacterial genomes associated with replication timing
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/2369bafe38c94f918a117fbaa84e404a
work_keys_str_mv	AT marcusmdillon periodicvariationofmutationratesinbacterialgenomesassociatedwithreplicationtiming AT waysung periodicvariationofmutationratesinbacterialgenomesassociatedwithreplicationtiming AT michaellynch periodicvariationofmutationratesinbacterialgenomesassociatedwithreplicationtiming AT vaughnscooper periodicvariationofmutationratesinbacterialgenomesassociatedwithreplicationtiming
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Periodic Variation of Mutation Rates in Bacterial Genomes Associated with Replication Timing

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