scholarly journals Periodic variation of mutation rates in bacterial genomes associated with replication timing

2017 ◽  
Author(s):  
Marcus M. Dillon ◽  
Way Sung ◽  
Michael Lynch ◽  
Vaughn S. Cooper
Keyword(s):  
Vibrio Fischeri ◽  
Bacterial Species ◽  
Replication Timing ◽  
Small Chromosome ◽  
Burkholderia Cenocepacia ◽  
Mutation Rates ◽  
Base Substitution ◽  
Large Chromosome ◽  
Bacterial Genomes ◽  
Substitution Mutation

ABSTRACTThe causes and consequences of spatiotemporal variation in mutation rates remains 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, andBurkholderia cenocepacia. Following five evolution 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 chromosome ofV. fischeriandV. 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 as 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.

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

mBio ◽  
2018 ◽  
Vol 9 (4) ◽  
Author(s):  
Marcus M. Dillon ◽  
Way Sung ◽  
Michael Lynch ◽  
Vaughn S. Cooper
Keyword(s):  
Bacterial Species ◽  
Replication Timing ◽  
Burkholderia Cenocepacia ◽  
Mutation Rates ◽  
Base Substitution ◽  
Large Chromosome ◽  
Rate Variation ◽  
Bacterial Genomes ◽  
Content Type ◽  
Substitution Mutation

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.

scholarly journals Genome-wide biases in the rate and molecular spectrum of spontaneous mutations in Vibrio cholerae and Vibrio fischeri

2016 ◽  
Author(s):  
Marcus M Dillon ◽  
Way Sung ◽  
Robert Sebra ◽  
Michael Lynch ◽  
Vaughn Cooper
Keyword(s):  
Vibrio Cholerae ◽  
Vibrio Fischeri ◽  
Purifying Selection ◽  
Base Substitution ◽  
Chromosome 2 ◽  
Spontaneous Mutations ◽  
Wild Type ◽  
Bacterial Genomes ◽  
Genome Wide ◽  
Mutation Spectra

The vast diversity in nucleotide composition and architecture among bacterial genomes may be partly explained by inherent biases in the rates and spectra of spontaneous mutations. Bacterial genomes with multiple chromosomes are relatively unusual but some are relevant to human health, none more so than the causative agent of cholera, Vibrio cholerae. Here, we present the genome-wide mutation spectra in wild-type and mismatch repair (MMR) defective backgrounds of two Vibrio species, the low-GC% squid symbiont V. fischeri and the pathogen V. cholerae, collected under conditions that greatly minimize the efficiency of natural selection. In apparent contrast to their high diversity in nature, both wild-type V. fischeri and V. cholerae have among the lowest rates for base-substitution mutations (bpsms) and insertion-deletion mutations (indels) that have been measured, below 10-3/genome/generation. V. fischeri and V. cholerae have distinct mutation spectra, but both are AT-biased and produce a surprising number of multi-nucleotide indels. Furthermore, the loss of a functional MMR system caused the mutation spectra of these species to converge, implying that the MMR system itself contributes to species-specific mutation patterns. Bpsm and indel rates varied among genome regions, but do not explain the more rapid evolutionary rates of genes on chromosome 2, which likely result from weaker purifying selection. More generally, the very low mutation rates of Vibrio species correlate inversely with their immense population sizes and suggest that selection may not only have maximized replication fidelity but also optimized other polygenic traits relative to the constraints of genetic drift.

scholarly journals GC-content evolution in bacterial genomes: the biased gene conversion hypothesis expands.

2014 ◽  
Author(s):  
Florent Lassalle ◽  
Séverine Périan ◽  
Thomas Bataillon ◽  
Xavier Nesme ◽  
Laurent Duret ◽  
...  
Keyword(s):  
Gene Conversion ◽  
Bacterial Species ◽  
Gc Content ◽  
Base Substitution ◽  
Human Populations ◽  
Bacterial Genomes ◽  
Evolutionary Forces ◽  
Evolutionary Force ◽  
Biased Gene Conversion ◽  
Genomic Regions

The characterization of functional elements in genomes relies on the identification of the footprints of natural selection. In this quest, taking into account neutral evolutionary processes such as mutation and genetic drift is crucial because these forces can generate patterns that may obscure or mimic signatures of selection. In mammals, and probably in many eukaryotes, another such confounding factor called GC-Biased Gene Conversion (gBGC) has been documented. This mechanism generates patterns identical to what is expected under selection for higher GC-content, specifically in highly recombining genomic regions. Recent results have suggested that a mysterious selective force favouring higher GC-content exists in Bacteria but the possibility that it could be gBGC has been excluded. Here, we show that gBGC is probably at work in most if not all bacterial species. First we find a consistent positive relationship between the GC-content of a gene and evidence of intra-genic recombination throughout a broad spectrum of bacterial clades. Second, we show that the evolutionary force responsible for this pattern is acting independently from selection on codon usage, and could potentially interfere with selection in favor of optimal AU-ending codons. A comparison with data from human populations shows that the intensity of gBGC in Bacteria is comparable to what has been reported in mammals. We propose that gBGC is not restricted to sexual Eukaryotes but also widespread among Bacteria and could therefore be an ancestral feature of cellular organisms. We argue that if gBGC occurs in bacteria, it can account for previously unexplained observations, such as the apparent non-equilibrium of base substitution patterns and the heterogeneity of gene composition within bacterial genomes. Because gBGC produces patterns similar to positive selection, it is essential to take this process into account when studying the evolutionary forces at work in bacterial genomes.

scholarly journals Low base-substitution mutation rate in the germline genome of the ciliate Tetrahymena thermophila

2015 ◽  
Author(s):  
Hongan Long ◽  
David J. Winter ◽  
Allan Y.-C Chang ◽  
Way Sung ◽  
Steven H. Wu ◽  
...  
Keyword(s):  
Mutation Rate ◽  
Tetrahymena Thermophila ◽  
Mutation Rates ◽  
Base Substitution ◽  
Paramecium Tetraurelia ◽  
Epigenetic Factors ◽  
Detection Approach ◽  
Evolution Experiment ◽  
Substitution Mutations ◽  
Substitution Mutation

AbstractMutation is the ultimate source of all genetic variation and is, therefore, central to evolutionary change. Previous work on Paramecium tetraurelia found an unusually low germline base-substitution mutation rate in this ciliate. Here, we tested the generality of this result among ciliates using Tetrahymena thermophila. We sequenced the genomes of 10 lines of T. thermophila that had each undergone approximately 1,000 generations of mutation accumulation (MA). We applied an existing mutation-calling pipeline and developed a new probabilistic mutation detection approach that directly models the design of an MA experiment and accommodates the noise introduced by mismapped reads. Our probabilistic mutation-calling method provides a straightforward way of estimating the number of sites at which a mutation could have been called if one was present, providing the denominator for our mutation rate calculations. From these methods, we find that T. thermophila has a germline base-substitution mutation rate of 7.61 × 10−12 per site, per cell division, which is consistent with the low base-substitution mutation rate in P. tetraurelia. Over the course of the evolution experiment, genomic exclusion lines derived from the MA lines experienced a fitness decline that cannot be accounted for by germline base-substitution mutations alone, suggesting that other genetic or epigenetic factors must be involved. Because selection can only operate to reduce mutation rates based upon the “visible” mutational load, asexual reproduction with a transcriptionally silent germline may allow ciliates to evolve extremely low germline mutation rates.

scholarly journals Expression of theEscherichia coli ftsZgene: trials and tribulations of gene fusion studies

1993 ◽  
Vol 61 (1) ◽  
pp. 1-8
Author(s):  
Aline Robin ◽  
Richard D'Ari
Keyword(s):  
Gene Fusion ◽  
Open Reading Frame ◽  
Mutation Rates ◽  
Base Substitution ◽  
Reading Frame ◽  
E Coli ◽  
New Gene ◽  
Cell Division Protein ◽  
Selection For ◽  
Substitution Mutation

SummaryTheftsZgene ofEscherichia coli, which codes for an essential cell division protein, is subjected to multiple regulation, as shown in part with studies using anftsZ::lacZoperon fusion located on phage λJFLIOO. Using this same fusion, we sought to isolate regulatory mutants overexpressingftsZby selecting mutants able to grow on lactose. One Lac+mutant was obtained which overexpressed theftsZ::lacZfusion 70-fold. The mutation responsible for the overexpression lies in a new gene,cot, located near 56 min on theE. coligenetic map. Thecotmutation probably affects the transcription of a chromosomal open reading frame, 0RF1, lying downstream of thebioAgene and adjacent to theftzZ::lacZfusion of the λJFL100 prophage integrated atattλ. Using anftsZ84(Ts) strain, in which there was a double selection for overexpression of bothftsZ::lacZandftsZ+, no Lac+Tr mutants were obtained from 3·6 × 1010bacteria; the introduction of amutLallele, increasing spontaneous base substitution mutation rates 75-fold, did not permit us to isolate such a mutant. We conclude that Lac+ftsZ-constitutive mutations cannot be obtained in λJFL100 lysogens by a single base substitution.

scholarly journals The symmetrical pattern of base-pair substitutions rates across the chromosome in Escherichia coli has multiple causes

2019 ◽  
Author(s):  
Brittany A. Niccum ◽  
Heewook Lee ◽  
Wazim MohammedIsmail ◽  
Haixu Tang ◽  
Patricia L. Foster
Keyword(s):  
Escherichia Coli ◽  
Base Pair ◽  
Bacterial Species ◽  
Replication Timing ◽  
Mutation Rates ◽  
Whole Genome ◽  
Origin Of Replication ◽  
Symmetrical Pattern ◽  
Major Factors ◽  
Eukaryotic Genomes

AbstractMutation accumulation experiments followed by whole-genome sequencing have revealed that for several bacterial species the rate of base-pair substitutions is not constant across the chromosome but varies in a wave-like pattern symmetrical about the origin of replication. The experiments reported here demonstrate that in Escherichia coli several interacting factors determine the wave. Perturbing replication timing, progression, or the structure of the terminus disrupts the pattern. Biases in error-correction by proofreading and mismatch repair are major factors. The activities of the nucleoid binding proteins, HU and Fis, are important, suggesting that mutation rates increase when highly structured DNA is replicated. These factors should apply to most bacterial, and possibly eukaryotic, genomes, and imply that different areas of the genome evolve at different rates.

scholarly journals Consistent Metagenome-Derived Metrics Verify and Delineate Bacterial Species Boundaries

mSystems ◽  
2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Matthew R. Olm ◽  
Alexander Crits-Christoph ◽  
Spencer Diamond ◽  
Adi Lavy ◽  
Paula B. Matheus Carnevali ◽  
...  
Keyword(s):  
Bacterial Diversity ◽  
Ribosomal Proteins ◽  
Large Scale ◽  
Bacterial Species ◽  
Bacterial Genome ◽  
16S Rrna Genes ◽  
Rrna Genes ◽  
Species Discrimination ◽  
Bacterial Genomes ◽  
Discrimination Power

ABSTRACT Longstanding questions relate to the existence of naturally distinct bacterial species and genetic approaches to distinguish them. Bacterial genomes in public databases form distinct groups, but these databases are subject to isolation and deposition biases. To avoid these biases, we compared 5,203 bacterial genomes from 1,457 environmental metagenomic samples to test for distinct clouds of diversity and evaluated metrics that could be used to define the species boundary. Bacterial genomes from the human gut, soil, and the ocean all exhibited gaps in whole-genome average nucleotide identities (ANI) near the previously suggested species threshold of 95% ANI. While genome-wide ratios of nonsynonymous and synonymous nucleotide differences (dN/dS) decrease until ANI values approach ∼98%, two methods for estimating homologous recombination approached zero at ∼95% ANI, supporting breakdown of recombination due to sequence divergence as a species-forming force. We evaluated 107 genome-based metrics for their ability to distinguish species when full genomes are not recovered. Full-length 16S rRNA genes were least useful, in part because they were underrecovered from metagenomes. However, many ribosomal proteins displayed both high metagenomic recoverability and species discrimination power. Taken together, our results verify the existence of sequence-discrete microbial species in metagenome-derived genomes and highlight the usefulness of ribosomal genes for gene-level species discrimination. IMPORTANCE There is controversy about whether bacterial diversity is clustered into distinct species groups or exists as a continuum. To address this issue, we analyzed bacterial genome databases and reports from several previous large-scale environment studies and identified clear discrete groups of species-level bacterial diversity in all cases. Genetic analysis further revealed that quasi-sexual reproduction via horizontal gene transfer is likely a key evolutionary force that maintains bacterial species integrity. We next benchmarked over 100 metrics to distinguish these bacterial species from each other and identified several genes encoding ribosomal proteins with high species discrimination power. Overall, the results from this study provide best practices for bacterial species delineation based on genome content and insight into the nature of bacterial species population genetics.

scholarly journals Tandem Repeats in Bacillus: Unique Features and Taxonomic Distribution

2021 ◽  
Vol 22 (10) ◽  
pp. 5373
Author(s):  
Juan A. Subirana ◽  
Xavier Messeguer
Keyword(s):  
Tandem Repeats ◽  
Bacterial Species ◽  
Individual Species ◽  
Large Set ◽  
Bacterial Genomes ◽  
Rna Molecules ◽  
Variable Sequence ◽  
Repeat Size ◽  
Genomic Studies ◽  
Dna Tandem Repeats

Little is known about DNA tandem repeats across prokaryotes. We have recently described an enigmatic group of tandem repeats in bacterial genomes with a constant repeat size but variable sequence. These findings strongly suggest that tandem repeat size in some bacteria is under strong selective constraints. Here, we extend these studies and describe tandem repeats in a large set of Bacillus. Some species have very few repeats, while other species have a large number. Most tandem repeats have repeats with a constant size (either 52 or 20–21 nt), but a variable sequence. We characterize in detail these intriguing tandem repeats. Individual species have several families of tandem repeats with the same repeat length and different sequence. This result is in strong contrast with eukaryotes, where tandem repeats of many sizes are found in any species. We discuss the possibility that they are transcribed as small RNA molecules. They may also be involved in the stabilization of the nucleoid through interaction with proteins. We also show that the distribution of tandem repeats in different species has a taxonomic significance. The data we present for all tandem repeats and their families in these bacterial species will be useful for further genomic studies.

scholarly journals Metagenomic profiling of host-associated bacteria from 8 datasets of the red alga Porphyra purpurea, with MetaPhlAn 3.0

2020 ◽  
Author(s):  
Orestis Nousias ◽  
Federica Montesanto
Keyword(s):  
16S Rrna ◽  
Bacterial Species ◽  
Reference Database ◽  
Marker Genes ◽  
Specific Marker ◽  
Bacterial Genomes ◽  
Associated Bacteria ◽  
Pan Genome ◽  
Nucleotide Database ◽  
Porphyra Purpurea

AbstractMicrobial communities play a fundamental role in the association with marine algae, in fact they are recognized to be actively involved in growth and morphogenesis.Porphyra purpurea is a red algae commonly found in the intertidal zone with an high economical value, indeed several species belonging to the genus Porphyra are intensely cultivated in the Eastern Asian countries. Moreover, P. purpurea is widely used as model species in different fields, mainly due to its peculiar life cycle. Despite of that, little is known about the microbial community associated to this species. Here we report the microbial-associated diversity of P. purpurea in four different localities (Ireland, Italy United Kingdom and USA) through the analysis of eight metagenomic datasets obtained from the publicly available metagenomic nucleotide database (https://www.ebi.ac.uk/ena/). The metagenomic datasets were quality controlled with FastQC version 0.11.8, pre-processed with Trimmomatic version 0.39 and analysed with Methaplan 3.0, with a reference database containing clade specific marker genes from ~ 99.500 bacterial genomes, following the pan-genome approach, in order to identify the putative bacterial taxonomies and their relative abundances. Furthermore, we compared the results to the 16S rRNA metagenomic analysis pipeline of MGnify database to evaluate the effectiveness of the two methods. Out of the 43 bacterial species identified with MetaPhlAn 3.0 only 5 were common with the MGnify results and from the 21 genera, only 9 were common. This approach highlighted the different taxonomical resolution of a 16S rRNA OTU-based method in contrast to the pan-genome approach deployed by MetaPhlAn 3.0.

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