scholarly journals Optimal number of spacers in CRISPR arrays

2017 ◽  
Author(s):  
Alexander Martynov ◽  
Konstantin Severinov ◽  
Yaroslav Ispolatov
Keyword(s):  
Adaptive Immunity ◽  
Mutation Rate ◽  
Bacterial Genome ◽  
Molecular Machines ◽  
Optimal Number ◽  
Evolutionary Models ◽  
Bacterial Survival ◽  
Crispr Array ◽  
Viral Mutation ◽  
Huge Variety

AbstractWe estimate the number of spacers in a CRISPR array of a bacterium which maximizes its protection against a viral attack. The optimality follows from a competition between two trends: too few distinct spacers make the bacteria vulnerable to an attack by a virus with mutated corresponding protospacers, while an excessive variety of spacers dilutes the number of the CRISPR complexes armed with the most recent and thus most effective spacers. We first evaluate the optimal number of spacers in a simple scenario of an infection by a single viral species and later consider a more general case of multiple viral species. We find that depending on such parameters as the concentration of CRISPR-CAS interference complexes and its preference to arm with more recently acquired spacers, the rate of viral mutation, and the number of viral species, the predicted optimal array length lies within a range quite reasonable from the viewpoint of recent experiments.Author summaryCRISPR-Cas system is an adaptive immunity defense in bacteria and archaea against viruses. It works by accumulating in bacterial genome an array of spacers, or fragments of virus DNA from previous attacks. By matching spacers to corresponding parts of virus DNA called protospacers, CRISPR-Cas system identifies and destroys intruder DNA. Here we theoretically estimate the number of spacers that maximizes bacterial survival. This optimum emerges from a competition between two trends: More spacers allow a bacterium to hedge against mutations in viral protospacers. However, keeping too many spacers makes the older ones inefficient because of accumulation of mutations in corresponding protospacers in viruses. Thus, fewer CRISPR-Cas molecular machines are left armed with more efficient young spacers. We have shown that a higher efficiency of CRISPR-Cas system allows a bacterium to utilize more spacers, increasing the optimal array length. On contrary, a higher viral mutation rate makes older spacers useless and favors shorter arrays. A higher diversity in viral species reduces the efficiency of CRISPR-Cas but does not necessary lead to longer arrays. We think that our study provides a new viewpoint at a huge variety in the observed array lengths and adds relevance to evolutionary models of bacterial-phage coexistence.

scholarly journals Viral Mutation Rates

2010 ◽  
Vol 84 (19) ◽  
pp. 9733-9748 ◽  
Author(s):  
Rafael Sanjuán ◽  
Miguel R. Nebot ◽  
Nicola Chirico ◽  
Louis M. Mansky ◽  
Robert Belshaw
Keyword(s):  
Mutation Rate ◽  
Rna Viruses ◽  
Experimental Testing ◽  
Mutation Rates ◽  
Cell Infection ◽  
Nucleotide Substitutions ◽  
Data Set ◽  
Dna Viruses ◽  
Double Stranded Dna ◽  
Viral Mutation

ABSTRACT Accurate estimates of virus mutation rates are important to understand the evolution of the viruses and to combat them. However, methods of estimation are varied and often complex. Here, we critically review over 40 original studies and establish criteria to facilitate comparative analyses. The mutation rates of 23 viruses are presented as substitutions per nucleotide per cell infection (s/n/c) and corrected for selection bias where necessary, using a new statistical method. The resulting rates range from 10−8 to10−6 s/n/c for DNA viruses and from 10−6 to 10−4 s/n/c for RNA viruses. Similar to what has been shown previously for DNA viruses, there appears to be a negative correlation between mutation rate and genome size among RNA viruses, but this result requires further experimental testing. Contrary to some suggestions, the mutation rate of retroviruses is not lower than that of other RNA viruses. We also show that nucleotide substitutions are on average four times more common than insertions/deletions (indels). Finally, we provide estimates of the mutation rate per nucleotide per strand copying, which tends to be lower than that per cell infection because some viruses undergo several rounds of copying per cell, particularly double-stranded DNA viruses. A regularly updated virus mutation rate data set will be available at www.uv.es/rsanjuan/virmut .

scholarly journals Genome-Wide Mutation Rate Response to pH Change in the Coral Reef Pathogen Vibrio shilonii AK1

mBio ◽  
2017 ◽  
Vol 8 (4) ◽  
Author(s):  
Chloe Strauss ◽  
Hongan Long ◽  
Caitlyn E. Patterson ◽  
Ronald Te ◽  
Michael Lynch
Keyword(s):  
Coral Reef ◽  
Mutation Rate ◽  
Ph Dependence ◽  
Bacterial Genome ◽  
Mutation Spectrum ◽  
Ph Change ◽  
Evolutionary Forces ◽  
Marine Habitats ◽  
Genome Wide ◽  
Evolutionary Features

ABSTRACT Recent application of mutation accumulation techniques combined with whole-genome sequencing (MA/WGS) has greatly promoted studies of spontaneous mutation. However, such explorations have rarely been conducted on marine organisms, and it is unclear how marine habitats have influenced genome stability. This report resolves the mutation rate and spectrum of the coral reef pathogen Vibrio shilonii, which causes coral bleaching and endangers the biodiversity maintained by coral reefs. We found that its mutation rate and spectrum are highly similar to those of other studied bacteria from various habitats, despite the saline environment. The mutational properties of this marine bacterium are thus controlled by other general evolutionary forces such as natural selection and genetic drift. We also found that as pH drops, the mutation rate decreases and the mutation spectrum is biased in the direction of generating G/C nucleotides. This implies that evolutionary features of this organism and perhaps other marine microbes might be altered by the increasingly acidic ocean water caused by excess CO2 emission. Nonetheless, further exploration is needed as the pH range tested in this study was rather narrow and many other possible mutation determinants, such as carbonate increase, are associated with ocean acidification. IMPORTANCE This study explored the pH dependence of a bacterial genome-wide mutation rate. We discovered that the genome-wide rates of appearance of most mutation types decrease linearly and that the mutation spectrum is biased in generating more G/C nucleotides with pH drop in the coral reef pathogen V. shilonii. This study explored the pH dependence of a bacterial genome-wide mutation rate. We discovered that the genome-wide rates of appearance of most mutation types decrease linearly and that the mutation spectrum is biased in generating more G/C nucleotides with pH drop in the coral reef pathogen V. shilonii.

scholarly journals Viral Diversity Threshold for Adaptive Immunity in Prokaryotes

mBio ◽  
2012 ◽  
Vol 3 (6) ◽  
Author(s):  
Ariel D. Weinberger ◽  
Yuri I. Wolf ◽  
Alexander E. Lobkovsky ◽  
Michael S. Gilmore ◽  
Eugene V. Koonin
Keyword(s):  
Mathematical Modeling ◽  
Adaptive Immunity ◽  
Plasmid Dna ◽  
Immunological Memory ◽  
Mutation Rates ◽  
Viral Diversity ◽  
Dna Fragments ◽  
Immune Systems ◽  
Mesophilic Bacteria ◽  
Viral Mutation

ABSTRACT Bacteria and archaea face continual onslaughts of rapidly diversifying viruses and plasmids. Many prokaryotes maintain adaptive immune systems known as clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated genes (Cas). CRISPR-Cas systems are genomic sensors that serially acquire viral and plasmid DNA fragments (spacers) that are utilized to target and cleave matching viral and plasmid DNA in subsequent genomic invasions, offering critical immunological memory. Only 50% of sequenced bacteria possess CRISPR-Cas immunity, in contrast to over 90% of sequenced archaea. To probe why half of bacteria lack CRISPR-Cas immunity, we combined comparative genomics and mathematical modeling. Analysis of hundreds of diverse prokaryotic genomes shows that CRISPR-Cas systems are substantially more prevalent in thermophiles than in mesophiles. With sequenced bacteria disproportionately mesophilic and sequenced archaea mostly thermophilic, the presence of CRISPR-Cas appears to depend more on environmental temperature than on bacterial-archaeal taxonomy. Mutation rates are typically severalfold higher in mesophilic prokaryotes than in thermophilic prokaryotes. To quantitatively test whether accelerated viral mutation leads microbes to lose CRISPR-Cas systems, we developed a stochastic model of virus-CRISPR coevolution. The model competes CRISPR-Cas-positive (CRISPR-Cas+) prokaryotes against CRISPR-Cas-negative (CRISPR-Cas−) prokaryotes, continually weighing the antiviral benefits conferred by CRISPR-Cas immunity against its fitness costs. Tracking this cost-benefit analysis across parameter space reveals viral mutation rate thresholds beyond which CRISPR-Cas cannot provide sufficient immunity and is purged from host populations. These results offer a simple, testable viral diversity hypothesis to explain why mesophilic bacteria disproportionately lack CRISPR-Cas immunity. More generally, fundamental limits on the adaptability of biological sensors (Lamarckian evolution) are predicted. IMPORTANCE A remarkable recent discovery in microbiology is that bacteria and archaea possess systems conferring immunological memory and adaptive immunity. Clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated genes (CRISPR-Cas) are genomic sensors that allow prokaryotes to acquire DNA fragments from invading viruses and plasmids. Providing immunological memory, these stored fragments destroy matching DNA in future viral and plasmid invasions. CRISPR-Cas systems also provide adaptive immunity, keeping up with mutating viruses and plasmids by continually acquiring new DNA fragments. Surprisingly, less than 50% of mesophilic bacteria, in contrast to almost 90% of thermophilic bacteria and Archaea, maintain CRISPR-Cas immunity. Using mathematical modeling, we probe this dichotomy, showing how increased viral mutation rates can explain the reduced prevalence of CRISPR-Cas systems in mesophiles. Rapidly mutating viruses outrun CRISPR-Cas immune systems, likely decreasing their prevalence in bacterial populations. Thus, viral adaptability may select against, rather than for, immune adaptability in prokaryotes.

scholarly journals CRISPR-Cas: a brief overview

KIDNEYS ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 2-3
Author(s):  
Yusuf Ercin Sonmez
Keyword(s):  
Adaptive Immunity ◽  
Congenital Abnormalities ◽  
Congenital Diseases ◽  
Crispr Array ◽  
The Future ◽  
Cas A

CRISPR-Cas is an adaptive immunity in prokaryotes against infections by viruses and plasmids. CRISPR array recognizes foreign sequences of the invaders and Cas destroys them. Using this system seems possible to find the unwanted sequences in the genome and to destroy or to change them with the suitable ones. This system might not only protect ourselves from the future infections but also correct congenital abnormalities which may predispose to carcinogenesis or some congenital diseases.

scholarly journals Signals of variation in human mutation rate at multiple levels of sequence context

2018 ◽  
Author(s):  
Rachael C. Aikens ◽  
Kelsey E. Johnson ◽  
Benjamin F. Voight
Keyword(s):  
Mutation Rate ◽  
Rate Variation ◽  
Evolutionary Models ◽  
Base Pairs ◽  
Sequence Context ◽  
Local Sequence ◽  
Multiple Levels ◽  
Human Mutation ◽  
Genetic Context ◽  
Mutation Rate Variation

ABSTRACTOur understanding of mutation rate helps us build evolutionary models and make sense of genetic variation. Recent work indicates that the frequencies of specific mutation types have been elevated in Europe, and that many more, subtler signatures of global polymorphism variation may yet remain unidentified. Here, we present an analysis of the 1,000 Genomes Project (phase 3), suggesting additional putative signatures of mutation rate variation across populations and the extent to which they are shaped by local sequence context. First, we compiled a list of the most significantly variable polymorphism types in a cross-continental statistical test. Clustering polymorphisms together, we observed four sets of substitution types that showed similar trends of relative mutation rate across populations, and describe the patterns of these mutational clusters among continental groups. For the majority of these signatures, we found that a single flanking base pair of sequence context was sufficient to determine the majority of enrichment or depletion of a mutation type. However, local genetic context up to 2-3 base pairs away contributes additional variability, and helps to interpret a previously noted enrichment of certain polymorphism types in some East Asian groups. Building our understanding of mutation rate in this way can help us to construct more accurate evolutionary models and better understand the mechanisms that underlie genetic change.

scholarly journals Quality control of low-frequency variants in SARS-CoV-2 genomes

2020 ◽  
Author(s):  
Mikhail Rayko ◽  
Aleksey Komissarov
Keyword(s):  
Quality Control ◽  
Mutation Rate ◽  
Low Frequency ◽  
Comprehensive Analysis ◽  
Tree Topology ◽  
Viral Mutation ◽  
Variant Frequency ◽  
Current Outbreak ◽  
Lower Transition

AbstractDuring the current outbreak of COVID-19, research labs around the globe submit sequences of the local SARS-CoV-2 genomes to the GISAID database to provide a comprehensive analysis of the variability and spread of the virus during the outbreak. We explored the variations in the submitted genomes and found a significant number of variants that can be seen only in one submission (singletons). While it is not completely clear whether these variants are erroneous or not, these variants show lower transition/transversion ratio. These singleton variants may influence the estimations of the viral mutation rate and tree topology. We suggest that genomes with multiple singletons even marked as high-covered should be considered with caution. We also provide a simple script for checking variant frequency against the database before submission.

scholarly journals Predicted highly derived class 1 CRISPR-Cas system in Haloarchaea containing diverged Cas5 and Cas7 homologs but no CRISPR array

2019 ◽  
Vol 366 (7) ◽  
Author(s):  
Kira S Makarova ◽  
Svetlana Karamycheva ◽  
Shiraz A Shah ◽  
Gisle Vestergaard ◽  
Roger A Garrett ◽  
...  
Keyword(s):  
Adaptive Immunity ◽  
Defense Mechanism ◽  
Crispr Array ◽  
Class 1

ABSTRACT Screening of genomic and metagenomic databases for new variants of CRISPR-Cas systems increasingly results in the discovery of derived variants that do not seem to possess the interference capacity and are implicated in functions distinct from adaptive immunity. We describe an extremely derived putative class 1 CRISPR-Cas system that is present in many Halobacteria and consists of distant homologs of the Cas5 and Cas7 protein along with an uncharacterized conserved protein and various nucleases. We hypothesize that, although this system lacks typical CRISPR effectors or a CRISPR array, it functions as a RNA-dependent defense mechanism that, unlike other derived CRISPR-Cas, utilizes alternative nucleases to cleave invader genomes.

scholarly journals Probability of consolidation constrains novel serotype emergence in dengue fever virus

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0248765
Author(s):  
Gilberto Sánchez-González ◽  
Zachery R. Belak ◽  
Luis Lozano ◽  
Renaud Condé
Keyword(s):  
Dengue Virus ◽  
Mutation Rate ◽  
Rna Virus ◽  
Mechanistic Explanation ◽  
Transmission Model ◽  
Denv Serotypes ◽  
Viral Mutation ◽  
Virus Serotype ◽  
Low Probability ◽  
Mosquito Infection

Since their first sequencing 40 years ago, Dengue virus (DENV) genotypes have shown extreme coherence regarding the serotype class they encode. Considering that DENV is a ribonucleic acid (RNA) virus with a high mutation rate, this behavior is intriguing. Here, we explore the effect of various parameters on likelihood of new serotype emergence. In order to determine the time scales of such an event, we used a Timed Markov Transmission Model to explore the influences of sylvatic versus peri-urban transmission, viral mutation rate, and vertical transmission on the probabilities of novel serotype emergence. We found that around 1 000 years are required for a new serotype to emerge, consistent with phylogenetic analysis of extant dengue serotypes. Furthermore, we show that likelihood of establishing chains of mosquito-human-mosquito infection, known as consolidation, is the primary factor which constrains novel serotype emergence. Our work illustrates the restrictions on and provides a mechanistic explanation for the low probability of novel dengue virus serotype emergence and the low number of observed DENV serotypes.

scholarly journals Complexities of Viral Mutation Rates

2018 ◽  
Vol 92 (14) ◽  
Author(s):  
Kayla M. Peck ◽  
Adam S. Lauring
Keyword(s):  
Population Genetics ◽  
Mutation Rate ◽  
Mutation Rates ◽  
Rate Estimation ◽  
Viral Mutation ◽  
Context Dependent ◽  
Mutation Rate Estimation

ABSTRACT Many viruses evolve rapidly. This is due, in part, to their high mutation rates. Mutation rate estimates for over 25 viruses are currently available. Here, we review the population genetics of virus mutation rates. We specifically cover the topics of mutation rate estimation, the forces that drive the evolution of mutation rates, and how the optimal mutation rate can be context-dependent.

scholarly journals Reduced Mutation Rate and Increased Transformability of Transposon-Free Acinetobacter baylyi ADP1-ISx

2017 ◽  
Vol 83 (17) ◽  
Author(s):  
Gabriel A. Suárez ◽  
Brian A. Renda ◽  
Aurko Dasgupta ◽  
Jeffrey E. Barrick
Keyword(s):  
Mutation Rate ◽  
Spontaneous Mutation ◽  
Bacterial Genome ◽  
Mutation Rates ◽  
Mobile Dna ◽  
Wild Type ◽  
Acinetobacter Baylyi ◽  
Content Type ◽  
Is Elements ◽  
Dna Elements

ABSTRACT The genomes of most bacteria contain mobile DNA elements that can contribute to undesirable genetic instability in engineered cells. In particular, transposable insertion sequence (IS) elements can rapidly inactivate genes that are important for a designed function. We deleted all six copies of IS1236 from the genome of the naturally transformable bacterium Acinetobacter baylyi ADP1. The natural competence of ADP1 made it possible to rapidly repair deleterious point mutations that arose during strain construction. In the resulting ADP1-ISx strain, the rates of mutations inactivating a reporter gene were reduced by 7- to 21-fold. This reduction was higher than expected from the incidence of new IS1236 insertions found during a 300-day mutation accumulation experiment with wild-type ADP1 that was used to estimate spontaneous mutation rates in the strain. The extra improvement appears to be due in part to eliminating large deletions caused by IS1236 activity, as the point mutation rate was unchanged in ADP1-ISx. Deletion of an error-prone polymerase (dinP) and a DNA damage response regulator (umuDAb [the umuD gene of A. baylyi]) from the ADP1-ISx genome did not further reduce mutation rates. Surprisingly, ADP1-ISx exhibited increased transformability. This improvement may be due to less autolysis and aggregation of the engineered cells than of the wild type. Thus, deleting IS elements from the ADP1 genome led to a greater than expected increase in evolutionary reliability and unexpectedly enhanced other key strain properties, as has been observed for other clean-genome bacterial strains. ADP1-ISx is an improved chassis for metabolic engineering and other applications. IMPORTANCE Acinetobacter baylyi ADP1 has been proposed as a next-generation bacterial host for synthetic biology and genome engineering due to its ability to efficiently take up DNA from its environment during normal growth. We deleted transposable elements that are capable of copying themselves, inserting into other genes, and thereby inactivating them from the ADP1 genome. The resulting “clean-genome” ADP1-ISx strain exhibited larger reductions in the rates of inactivating mutations than expected from spontaneous mutation rates measured via whole-genome sequencing of lineages evolved under relaxed selection. Surprisingly, we also found that IS element activity reduces transformability and is a major cause of cell aggregation and death in wild-type ADP1 grown under normal laboratory conditions. More generally, our results demonstrate that domesticating a bacterial genome by removing mobile DNA elements that have accumulated during evolution in the wild can have unanticipated benefits.

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