scholarly journals Empirical estimates of the mutation rate for an alphabaculovirus

2021 ◽  
Author(s):  
Dieke Boezen ◽  
Ghulam Ali ◽  
Manli Wang ◽  
Xi Wang ◽  
Wopke van der Werf ◽  
...  
Keyword(s):  
Mutation Rate ◽  
Virus Genome ◽  
Good Evidence ◽  
Viral Fitness ◽  
Mutation Rates ◽  
Replication Machinery ◽  
Dna Viruses ◽  
Genome Data ◽  
Empirical Estimates ◽  
Large Genomes

AbstractMutation rates are of key importance for understanding evolutionary processes and predicting their outcomes. Empirical estimates of mutation rate are available for a number of RNA viruses, but few are available for DNA viruses, which tend to have larger genomes. Whilst some viruses have very high mutation rates, lower mutation rates are expected for viruses with large genomes to ensure genome integrity. Alphabaculoviruses are insect viruses with large genomes and often have high levels of polymorphism, suggesting high mutation rates despite evidence of proofreading activity by the replication machinery. Here, we report an empirical estimate of the mutation rate per base per strand copying (s/n/r) of Autographa californica multiple nucleopolyhedrovirus (AcMNPV). To avoid biases due to selection, we analyzed mutations that occurred in a stable, non-functional genomic insert after five serial passages in Spodoptera exigua larvae. Population bottlenecks, viral mode of replication and thresholds for mutation detection likely affect mutation rate estimates, and we therefore used population genetic models that account for these processes to infer the mutation rate. We estimated a mutation rate of 1×10−7 s/n/r. This estimate was not sensitive to different model assumptions or including whole genome data. The rates at which different classes of mutations accumulate provide good evidence for neutrality of mutations occurring within the inserted region. We therefore present a robust approach for mutation rate estimation for viruses with stable genomes, and strong evidence of a much lower alphabaculovirus mutation rate than supposed based on the high levels of polymorphism observed.Author SummaryVirus populations can evolve rapidly, driven by the large number of mutations that occur during virus replication. It is challenging to measure mutation rates because selection will affect which mutations are observed: beneficial mutations are overrepresented in virus populations, while deleterious mutations are selected against and therefore underrepresented. Few mutation rates have been estimated for viruses with large DNA genomes, and there are no estimates for any insect virus. Here, we estimate the mutation rate for an alphabaculovirus, a virus that infects caterpillars and has a large, 134 kilobase pair DNA genome. To ensure that selection did not bias our estimate of mutation rate, we studied which mutations occurred in a large artificial region inserted into the virus genome, where mutations did not affect viral fitness. We deep sequenced evolved virus populations, and compared the distribution of observed mutants to predictions from a simulation model to estimate mutation rate. We found evidence for a relatively low mutation rate, of one mutation in every 10 million bases replicated. This estimate is in line with expectations for a virus with self-correcting replication machinery and a large genome.

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 The mutation rates and mutational bias of influenza A virus

2017 ◽  
Author(s):  
Matthew D. Pauly ◽  
Megan Procario ◽  
Adam S. Lauring
Keyword(s):  
Influenza Virus ◽  
Influenza A Virus ◽  
Mutation Rate ◽  
Influenza A ◽  
Rapid Evolution ◽  
Viral Fitness ◽  
High Mutation Rate ◽  
Mutation Rates ◽  
Mutational Bias ◽  
Neutral Mutations

AbstractInfluenza virus has a high mutation rate, and this low replicative fidelity contributes to its capacity for rapid evolution. Clonal sequencing and fluctuation tests have suggested that the mutation rate of influenza A virus is 7.1 × 10−6− 4.5 × 10−5substitutions per nucleotide per cell infection cycle and 2.7 × 10−6− 3.0 × 10−5substitutions per nucleotide per strand copied (s/n/r). However, sequencing assays are biased toward mutations with minimal impacts on viral fitness and fluctuation tests typically investigate only a subset of the twelve mutational classes. We developed a fluctuation test based on reversion to fluorescence in a set of virally encoded mutant green fluorescent proteins. This method allowed us to measure the rates of selectively neutral mutations representative of all 12 mutational classes in the context of an unstructured RNA. We measured an overall mutation rate of 1.8 × 10−4s/n/r for PR8 (H1N1) and 2.5 × 10−4s/n/r for Hong Kong 2014 (H3N2). The replication mode was linear. The mutation rates of these divergent strains are significantly higher than previous estimates and suggest that each replicated genome will have an average of 2-3 mutations. The viral mutational spectrum is heavily biased toward A to G and U to C transitions, resulting in a transition to transversion bias of 2.7 and 3.6 for the two strains. These mutation rates were relatively constant over a range of physiological temperatures. Our high-resolution analysis of influenza virus mutation rates will enable more refined models of its molecular evolution.SignificanceThe rapid evolution of influenza virus is a major problem in public health. A key factor driving this rapid evolution is the virus’ very high mutation rate. We developed a new method for measuring the rates of all 12 mutational classes in influenza virus, which eliminates some of the biases of existing assays. We find that the influenza virus mutation rate is much higher than previously reported and is consistent across two distinct strains and a range of temperatures. Our data suggest that influenza viruses replicate at their maximally tolerable mutation rates, highlighting both the virus’ evolutionary potential and its significant constraints.

scholarly journals Intercellular Transmission of Naked Viruses through Extracellular Vesicles: Focus on Polyomaviruses

Viruses ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 1086
Author(s):  
Francois Helle ◽  
Lynda Handala ◽  
Marine Bentz ◽  
Gilles Duverlie ◽  
Etienne Brochot
Keyword(s):  
Immune System ◽  
Extracellular Vesicles ◽  
Rna Viruses ◽  
Viral Transmission ◽  
Viral Fitness ◽  
Host Cells ◽  
Dna Viruses ◽  
Recent Advances ◽  
Viral Particles ◽  
Similar Strategy

Extracellular vesicles have recently emerged as a novel mode of viral transmission exploited by naked viruses to exit host cells through a nonlytic pathway. Extracellular vesicles can allow multiple viral particles to collectively traffic in and out of cells, thus enhancing the viral fitness and diversifying the transmission routes while evading the immune system. This has been shown for several RNA viruses that belong to the Picornaviridae, Hepeviridae, Reoviridae, and Caliciviridae families; however, recent studies also demonstrated that the BK and JC viruses, two DNA viruses that belong to the Polyomaviridae family, use a similar strategy. In this review, we provide an update on recent advances in understanding the mechanisms used by naked viruses to hijack extracellular vesicles, and we discuss the implications for the biology of polyomaviruses.

VirusTaxo: Taxonomic classification of virus genome using multi-class hierarchical classification by k-mer enrichment

2021 ◽  
Author(s):  
Rajan Saha Raju ◽  
Abdullah Al Nahid ◽  
Preonath Shuvo ◽  
Rashedul Islam
Keyword(s):  
Genome Sequence ◽  
Rna Viruses ◽  
Hierarchical Classification ◽  
Classification Problem ◽  
Virus Genome ◽  
Taxonomic Classification ◽  
Dna Viruses ◽  
Dna And Rna ◽  
Full Length Genome

AbstractTaxonomic classification of viruses is a multi-class hierarchical classification problem, as taxonomic ranks (e.g., order, family and genus) of viruses are hierarchically structured and have multiple classes in each rank. Classification of biological sequences which are hierarchically structured with multiple classes is challenging. Here we developed a machine learning architecture, VirusTaxo, using a multi-class hierarchical classification by k-mer enrichment. VirusTaxo classifies DNA and RNA viruses to their taxonomic ranks using genome sequence. To assign taxonomic ranks, VirusTaxo extracts k-mers from genome sequence and creates bag-of-k-mers for each class in a rank. VirusTaxo uses a top-down hierarchical classification approach and accurately assigns the order, family and genus of a virus from the genome sequence. The average accuracies of VirusTaxo for DNA viruses are 99% (order), 98% (family) and 95% (genus) and for RNA viruses 97% (order), 96% (family) and 82% (genus). VirusTaxo can be used to detect taxonomy of novel viruses using full length genome or contig sequences.AvailabilityOnline version of VirusTaxo is available at https://omics-lab.com/virustaxo/.

scholarly journals Mutation rate analysis via parent–progeny sequencing of the perennial peach. II. No evidence for recombination-associated mutation

2016 ◽  
Vol 283 (1841) ◽  
pp. 20161785 ◽  
Author(s):  
Long Wang ◽  
Yanchun Zhang ◽  
Chao Qin ◽  
Dacheng Tian ◽  
Sihai Yang ◽  
...  
Keyword(s):  
Mutation Rate ◽  
Recombination Rate ◽  
Mutation Rates ◽  
Recombination Rates ◽  
Rate Analysis ◽  
A Genome ◽  
Break Points ◽  
New Mutations

Mutation rates and recombination rates vary between species and between regions within a genome. What are the determinants of these forms of variation? Prior evidence has suggested that the recombination might be mutagenic with an excess of new mutations in the vicinity of recombination break points. As it is conjectured that domesticated taxa have higher recombination rates than wild ones, we expect domesticated taxa to have raised mutation rates. Here, we use parent–offspring sequencing in domesticated and wild peach to ask (i) whether recombination is mutagenic, and (ii) whether domesticated peach has a higher recombination rate than wild peach. We find no evidence that domesticated peach has an increased recombination rate, nor an increased mutation rate near recombination events. If recombination is mutagenic in this taxa, the effect is too weak to be detected by our analysis. While an absence of recombination-associated mutation might explain an absence of a recombination–heterozygozity correlation in peach, we caution against such an interpretation.

Evolution of mutation rate and virulence among human retroviruses

1994 ◽  
Vol 346 (1317) ◽  
pp. 333-343 ◽  
Keyword(s):  
Immune System ◽  
Mutation Rate ◽  
Hiv Infections ◽  
Molecular Data ◽  
Mutation Rates ◽  
Rapid Progression ◽  
Human T Cell ◽  
Large Numbers ◽  
The Individual ◽  
Multicellular Organisms

High mutation rates are generally considered to be detrimental to the fitness of multicellular organisms because mutations untune finely tuned biological machinery. However, high mutation rates may be favoured by a need to evade an immune system that has been strongly stimulated to recognize those variants that reproduced earlier during the infection, hiv infections conform to this situation because they are characterized by large numbers of viruses that are continually breaking latency and large numbers that are actively replicating throughout a long period of infection. To be transmitted, HIVS are thus generally exposed to an immune system that has been activated to destroy them in response to prior viral replication in the individual. Increases in sexual contact should contribute to this predicament by favouring evolution toward relatively high rates of replication early during infection. Because rapid replication and high mutation rate probably contribute to rapid progression of infections to aids, the interplay of sexual activity, replication rate, and mutation rate helps explain why HIV-1 has only recently caused a lethal pandemic, even though molecular data suggest that it may have been present in humans for more than a century. This interplay also offers an explanation for geographic differences in progression to cancer found among infections due to the other major group of human retroviruses, human T-cell lymphotropic viruses (HTLV). Finally, it suggests ways in which we can use natural selection as a tool to control the aids pandemic and prevent similar pandemics from arising in the future.

scholarly journals Transfer RNA genes experience exceptionally elevated mutation rates

2018 ◽  
Vol 115 (36) ◽  
pp. 8996-9001 ◽  
Author(s):  
Bryan P. Thornlow ◽  
Josh Hough ◽  
Jacquelyn M. Roger ◽  
Henry Gong ◽  
Todd M. Lowe ◽  
...  
Keyword(s):  
Mutation Rate ◽  
Trna Gene ◽  
Gene Evolution ◽  
Purifying Selection ◽  
Mutation Rates ◽  
Model Organisms ◽  
Biological Synthesis ◽  
Human Populations ◽  
Trna Genes ◽  
Simple Method

Transfer RNAs (tRNAs) are a central component for the biological synthesis of proteins, and they are among the most highly conserved and frequently transcribed genes in all living things. Despite their clear significance for fundamental cellular processes, the forces governing tRNA evolution are poorly understood. We present evidence that transcription-associated mutagenesis and strong purifying selection are key determinants of patterns of sequence variation within and surrounding tRNA genes in humans and diverse model organisms. Remarkably, the mutation rate at broadly expressed cytosolic tRNA loci is likely between 7 and 10 times greater than the nuclear genome average. Furthermore, evolutionary analyses provide strong evidence that tRNA genes, but not their flanking sequences, experience strong purifying selection acting against this elevated mutation rate. We also find a strong correlation between tRNA expression levels and the mutation rates in their immediate flanking regions, suggesting a simple method for estimating individual tRNA gene activity. Collectively, this study illuminates the extreme competing forces in tRNA gene evolution and indicates that mutations at tRNA loci contribute disproportionately to mutational load and have unexplored fitness consequences in human populations.

Y-chromosomal microsatellite mutation rates: Differences in mutation rate between and within loci

2004 ◽  
Vol 23 (2) ◽  
pp. 117-124 ◽  
Author(s):  
B. Myhre Dupuy ◽  
M. Stenersen ◽  
T. Egeland ◽  
B. Olaisen
Keyword(s):  
Mutation Rate ◽  
Mutation Rates ◽  
Microsatellite Mutation

scholarly journals Short term but highly efficient Cas9 expression mediated by excisional system using adenovirus vector and Cre

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sayaka Nagamoto ◽  
Miyuki Agawa ◽  
Emi Tsuchitani ◽  
Kazunori Akimoto ◽  
Saki Kondo Matsushima ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Genome Editing ◽  
Adenovirus Vector ◽  
Virus Genome ◽  
Dna Viruses ◽  
Tissue Specific ◽  
B Virus ◽  
Tissue Specific Promoter ◽  
A Cell

AbstractGenome editing techniques such as CRISPR/Cas9 have both become common gene engineering technologies and have been applied to gene therapy. However, the problems of increasing the efficiency of genome editing and reducing off-target effects that induce double-stranded breaks at unexpected sites in the genome remain. In this study, we developed a novel Cas9 transduction system, Exci-Cas9, using an adenovirus vector (AdV). Cas9 was expressed on a circular molecule excised by the site-specific recombinase Cre and succeeded in shortening the expression period compared to AdV, which expresses the gene of interest for at least 6 months. As an example, we chose hepatitis B, which currently has more than 200 million carriers in the world and frequently progresses to liver cirrhosis or hepatocellular carcinoma. The efficiencies of hepatitis B virus genome disruption by Exci-Cas9 and Cas9 expression by AdV directly (Avec) were the same, about 80–90%. Furthermore, Exci-Cas9 enabled cell- or tissue-specific genome editing by expressing Cre from a cell- or tissue-specific promoter. We believe that Exci-Cas9 developed in this study is useful not only for resolving the persistent expression of Cas9, which has been a problem in genome editing, but also for eliminating long-term DNA viruses such as human papilloma virus.

scholarly journals Death and population dynamics affect mutation rate estimates and evolvability under stress in bacteria

2017 ◽  
Author(s):  
Antoine Frénoy ◽  
Sebastian Bonhoeffer
Keyword(s):  
Population Dynamics ◽  
Mutation Rate ◽  
Death Rate ◽  
Mutation Rates ◽  
Resistance Mutations ◽  
Bacterial Populations ◽  
Plasmid Segregation ◽  
Genome Wide ◽  
Response To Stress ◽  
Induced Mutagenesis

AbstractThe stress-induced mutagenesis paradigm postulates that in response to stress, bacteria increase their genome-wide mutation rate, in turn increasing the chances that a descendant is able to withstand the stress. This has implications for antibiotic treatment: exposure to sub-inhibitory doses of antibiotics has been reported to increase bacterial mutation rates, and thus probably the rate at which resistance mutations appear and lead to treatment failure.Measuring mutation rates under stress, however, is problematic, because existing methods assume there is no death. Yet sub-inhibitory stress levels may induce a substantial death rate. Death events need to be compensated by extra replication to reach a given population size, thus giving more opportunities to acquire mutations. We show that ignoring death leads to a systematic overestimation of mutation rates under stress.We developed a system using plasmid segregation to measure death and growth rates simultaneously in bacterial populations. We use it to replicate classical experiments reporting antibiotic-induced mutagenesis. We found that a substantial death rate occurs at the tested sub-inhibitory concentrations, and taking this death into account lowers and sometimes removes the signal for stress-induced mutagenesis. Moreover even when antibiotics increase mutation rate, sub-inhibitory treatments do not increase genetic diversity and evolvability, again because of effects of the antibiotics on population dynamics.Beside showing that population dynamic is a crucial but neglected parameter affecting evolvability, we provide better experimental and computational tools to study evolvability under stress, leading to a re-assessment of the magnitude and significance of the stress-induced mutagenesis paradigm.

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