scholarly journals Phylogenetic Evidence for the Rapid Evolution of Human B19 Erythrovirus

2006 ◽  
Vol 80 (7) ◽  
pp. 3666-3669 ◽  
Author(s):  
Laura A. Shackelton ◽  
Edward C. Holmes
Keyword(s):  
Host Cell ◽  
Evolutionary Dynamics ◽  
Rna Viruses ◽  
Rapid Evolution ◽  
Evolutionary Change ◽  
High Rate ◽  
Mutation Rates ◽  
Genome Replication ◽  
Nucleotide Substitutions ◽  
Viral Pathogen

ABSTRACT Human B19 erythrovirus is a ubiquitous viral pathogen, commonly infecting individuals before adulthood. As with all autonomous parvoviruses, its small single-stranded DNA genome is replicated with host cell machinery. While the mechanism of parvovirus genome replication has been studied in detail, the rate at which B19 virus evolves is unknown. By inferring the phylogenetic history and evolutionary dynamics of temporally sampled B19 sequences, we observed a surprisingly high rate of evolutionary change, at approximately 10−4 nucleotide substitutions per site per year. This rate is more typical of RNA viruses and suggests that high mutation rates are characteristic of the Parvoviridae.

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 Nucleoside Analogue Mutagenesis of a Single-Stranded DNA Virus: Evolution and Resistance

2012 ◽  
Vol 86 (18) ◽  
pp. 9640-9646 ◽  
Author(s):  
Pilar Domingo-Calap ◽  
Marianoel Pereira-Gómez ◽  
Rafael Sanjuán
Keyword(s):  
Nucleoside Analogue ◽  
Rna Viruses ◽  
Spontaneous Mutation ◽  
Chemical Mutagenesis ◽  
Mutation Rates ◽  
Nucleotide Substitutions ◽  
Single Stranded Dna ◽  
Dna Viruses ◽  
Population Extinction ◽  
Nucleotide Mutation

It has been well established that chemical mutagenesis has adverse fitness effects in RNA viruses, often leading to population extinction. This is mainly a consequence of the high RNA virus spontaneous mutation rates, which situate them close to the extinction threshold. Single-stranded DNA viruses are the fastest-mutating DNA-based systems, with per-nucleotide mutation rates close to those of some RNA viruses, but chemical mutagenesis has been much less studied in this type of viruses. Here, we serially passaged bacteriophage ϕX174 in the presence of the nucleoside analogue 5-fluorouracil (5-FU). We found that 5-FU was unable to trigger population extinction for the range of concentrations tested, but it negatively affected viral adaptability. The phage evolved partial drug resistance, and parallel nucleotide substitutions appearing in independently evolved lines were identified as candidate resistance mutations. Using site-directed mutagenesis, two single-nucleotide substitutions in the lysis protein E (T572C and A781G) were shown to be selectively advantageous in the presence of 5-FU. In RNA viruses, base analogue resistance is often mediated by changes in the viral polymerase, but this mechanism is not possible for ϕX174 and other single-stranded DNA viruses because they do not encode their own polymerase. In addition to increasing mutation rates, 5-FU produces a wide variety of cytotoxic effects at the levels of replication, transcription, and translation. We found that substitutions T572C and A781G lost their ability to confer 5-FU resistance after cells were supplemented with deoxythymidine, suggesting that their mechanism of action is at the DNA level. We hypothesize that regulation of lysis time may allow the virus to optimize progeny size in cells showing defects in DNA synthesis.

scholarly journals Viral replication modes in single-peak fitness landscapes: a dynamical systems analysis

2017 ◽  
Author(s):  
Joan Forners ◽  
J. Tomás Lázaro ◽  
Tomás Alarcón ◽  
Santiago F. Elena ◽  
Josep Sardanyés
Keyword(s):  
Evolutionary Dynamics ◽  
Fitness Landscape ◽  
Rna Viruses ◽  
Viral Rna ◽  
Mutation Rates ◽  
Single Peak ◽  
Lethal Mutagenesis ◽  
Error Catastrophe ◽  
Degradation Rates ◽  
Transcritical Bifurcations

Positive-sense, single-stranded RNA viruses are important pathogens infecting almost all types of organisms. Experimental evidences from mutant distributions and amplification kinetics of viral RNA suggest that these pathogens may follow different RNA replication modes, ranging from the stamping machine replication (SMR) to the geometric replication (GR) modes. Despite previous theoretical works have focused on the evolutionary dynamics of RNA viruses amplifying their genomes with different strategies, few is known in terms of the bifurcations and transitions involving error thresholds (mutation-induced dominance of mutants) and lethal mutagenesis (mutation-induced extinction of all sequences). Here we analyze a dynamical system describing the intracellular amplification of viral RNA genomes evolving on a single-peak fitness landscape focusing on three cases considering neutral, deleterious, and lethal mutants spectra. In our model, the different replication modes are introduced with parameter α: with α ≳ 0 for the SMR and α = 1 for the GR. We analytically derive the critical mutation rates causing lethal mutagenesis and error catastrophe, governed by transcritical bifurcations that depend on parameters α, k1 (replicative fitness of mutants), and on the spontaneous degradation rates of the sequences, ϵ. For the lethal case the critical mutation rate involving lethal mutagenesis is . Here, the SMR involves lower critical mutation rates, being the system more robust to lethal mutagenesis replicating closer to the GR mode. This result is also found for the neutral and deleterious cases, but for these later cases lethal mutagenesis can shift to the error catastrophe once the replication mode surpasses a threshold given by .

scholarly journals Viral RNA Mutations Are Region Specific and Increased by Ribavirin in a Full-Length Hepatitis C Virus Replication System

2002 ◽  
Vol 76 (17) ◽  
pp. 8505-8517 ◽  
Author(s):  
Ana Maria Contreras ◽  
Yoichi Hiasa ◽  
Wenping He ◽  
Adam Terella ◽  
Emmett V. Schmidt ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Rna Viruses ◽  
Full Length ◽  
Mutation Rates ◽  
Hcv Rna ◽  
Nucleotide Substitutions ◽  
Replication System ◽  
Error Catastrophe

ABSTRACT High rates of genetic variation ensure the survival of RNA viruses. Although this variation is thought to result from error-prone replication, RNA viruses must also maintain highly conserved genomic segments. A balance between conserved and variable viral elements is especially important in order for viruses to avoid “error catastrophe.” Ribavirin has been shown to induce error catastrophe in other RNA viruses. We therefore used a novel hepatitis C virus (HCV) replication system to determine relative mutation frequencies in variable and conserved regions of the HCV genome, and we further evaluated these frequencies in response to ribavirin. We sequenced the 5′ untranslated region (5′ UTR) and the core, E2 HVR-1, NS5A, and NS5B regions of replicating HCV RNA isolated from cells transfected with a T7 polymerase-driven full-length HCV cDNA plasmid containing a cis-acting hepatitis delta virus ribozyme to control 3′ cleavage. We found quasispecies in the E2 HVR-1 and NS5B regions of untreated replicating viral RNAs but not in conserved 5′ UTR, core, or NS5A regions, demonstrating that important cis elements regulate mutation rates within specific viral segments. Neither T7-driven replication nor sequencing artifacts produced these nucleotide substitutions in control experiments. Ribavirin broadly increased error generation, especially in otherwise invariant regions, indicating that it acts as an HCV RNA mutagen in vivo. Similar results were obtained in hepatocyte-derived cell lines. These results demonstrate the potential utility of our system for the study of intrinsic factors regulating genetic variation in HCV. Our results further suggest that ribavirin acts clinically by promoting nonviable HCV RNA mutation rates. Finally, the latter result suggests that our replication model may be useful for identifying agents capable of driving replicating virus into error catastrophe.

scholarly journals Rapid evolutionary dynamics of zucchini yellow mosaic virus

2008 ◽  
Vol 89 (4) ◽  
pp. 1081-1085 ◽  
Author(s):  
Heather E. Simmons ◽  
Edward C. Holmes ◽  
Andrew G. Stephenson
Keyword(s):  
Coat Protein ◽  
Mosaic Virus ◽  
Evolutionary Dynamics ◽  
Rna Viruses ◽  
Zucchini Yellow Mosaic Virus ◽  
Yellow Mosaic Virus ◽  
Nucleotide Substitutions ◽  
The Family ◽  
Coalescent Approach

Zucchini yellow mosaic virus (ZYMV) is an economically important virus of cucurbit crops. However, little is known about the rate at which this virus has evolved within members of the family Cucurbitaceae, or the timescale of its epidemiological history. Herein, we present the first analysis of the evolutionary dynamics of ZYMV. Using a Bayesian coalescent approach we show that the coat protein of ZYMV has evolved at a mean rate of 5.0×10−4 nucleotide substitutions per site, per year. Notably, this rate is equivalent to those observed in animal RNA viruses. Using the same approach we show that the lineages of ZYMV sampled here have an ancestry that dates back no more than 800 years, suggesting that human activities have played a central role in the dispersal of ZYMV. Finally, an analysis of phylogeographical structure provides strong evidence for the in situ evolution of ZYMV within individual countries.

scholarly journals Snapshots of a Non-Canonical RdRP in Action

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1260
Author(s):  
Diego S. Ferrero ◽  
Michela Falqui ◽  
Nuria Verdaguer
Keyword(s):  
Metal Ion ◽  
Rna Viruses ◽  
Ion Binding ◽  
Genome Replication ◽  
Metal Ion Binding ◽  
Insect Virus ◽  
X Ray ◽  
Template Strand ◽  
Nucleotide Incorporation ◽  
Elongation Process

RNA viruses typically encode their own RNA-dependent RNA polymerase (RdRP) to ensure genome replication and transcription. The closed “right hand” architecture of RdRPs encircles seven conserved structural motifs (A to G) that regulate the polymerization activity. The four palm motifs, arranged in the sequential order A to D, are common to all known template dependent polynucleotide polymerases, with motifs A and C containing the catalytic aspartic acid residues. Exceptions to this design have been reported in members of the Permutotetraviridae and Birnaviridae families of positive single stranded (+ss) and double-stranded (ds) RNA viruses, respectively. In these enzymes, motif C is located upstream of motif A, displaying a permuted C–A–B–D connectivity. Here we study the details of the replication elongation process in the non-canonical RdRP of the Thosea asigna virus (TaV), an insect virus from the Permutatetraviridae family. We report the X-ray structures of three replicative complexes of the TaV polymerase obtained with an RNA template-primer in the absence and in the presence of incoming rNTPs. The structures captured different replication events and allowed to define the critical interactions involved in: (i) the positioning of the acceptor base of the template strand, (ii) the positioning of the 3’-OH group of the primer nucleotide during RNA replication and (iii) the recognition and positioning of the incoming nucleotide. Structural comparisons unveiled a closure of the active site on the RNA template-primer binding, before rNTP entry. This conformational rearrangement that also includes the repositioning of the motif A aspartate for the catalytic reaction to take place is maintained on rNTP and metal ion binding and after nucleotide incorporation, before translocation.

scholarly journals Rapid evolution at the Drosophila telomere: transposable element dynamics at an intrinsically unstable locus

Genetics ◽  
2020 ◽  
Vol 217 (2) ◽  
Author(s):  
Michael P McGurk ◽  
Anne-Marie Dion-Côté ◽  
Daniel A Barbash
Keyword(s):  
Copy Number ◽  
Large Scale ◽  
Insertion Site ◽  
Rapid Evolution ◽  
Interspecific Variation ◽  
High Rate ◽  
Evolutionary Strategy ◽  
Control Mechanisms ◽  
Genetic Conflict ◽  
Number Variation

AbstractDrosophila telomeres have been maintained by three families of active transposable elements (TEs), HeT-A, TAHRE, and TART, collectively referred to as HTTs, for tens of millions of years, which contrasts with an unusually high degree of HTT interspecific variation. While the impacts of conflict and domestication are often invoked to explain HTT variation, the telomeres are unstable structures such that neutral mutational processes and evolutionary tradeoffs may also drive HTT evolution. We leveraged population genomic data to analyze nearly 10,000 HTT insertions in 85  Drosophila melanogaster genomes and compared their variation to other more typical TE families. We observe that occasional large-scale copy number expansions of both HTTs and other TE families occur, highlighting that the HTTs are, like their feral cousins, typically repressed but primed to take over given the opportunity. However, large expansions of HTTs are not caused by the runaway activity of any particular HTT subfamilies or even associated with telomere-specific TE activity, as might be expected if HTTs are in strong genetic conflict with their hosts. Rather than conflict, we instead suggest that distinctive aspects of HTT copy number variation and sequence diversity largely reflect telomere instability, with HTT insertions being lost at much higher rates than other TEs elsewhere in the genome. We extend previous observations that telomere deletions occur at a high rate, and surprisingly discover that more than one-third do not appear to have been healed with an HTT insertion. We also report that some HTT families may be preferentially activated by the erosion of whole telomeres, implying the existence of HTT-specific host control mechanisms. We further suggest that the persistent telomere localization of HTTs may reflect a highly successful evolutionary strategy that trades away a stable insertion site in order to have reduced impact on the host genome. We propose that HTT evolution is driven by multiple processes, with niche specialization and telomere instability being previously underappreciated and likely predominant.

EVOLUTION WITH ENDOGENOUS MUTATIONS

2005 ◽  
Vol 07 (02) ◽  
pp. 229-240 ◽  
Author(s):  
IVAR KOLSTAD
Keyword(s):  
Evolutionary Dynamics ◽  
Basin Of Attraction ◽  
Equilibrium Selection ◽  
Mutation Rates ◽  
And Control

Bergin and Lipman (1996) prove that equilibrium selection in the evolutionary dynamics of Kandori et al. (1993) and Young (1993), is not robust to variations in mutation rates across states. Specifically, a risk dominant equilibrium can be selected against if mutation rates are higher in its basin of attraction than elsewhere. Van Damme and Weibull (1998) model mutations as a compromise between payoff losses and control costs, which implies lower mutation rates in the risk dominant equilibrium. This paper argues that this result is not driven by control costs, but by players focusing on payoff losses when choosing mutation rates.

scholarly journals Rapid evolution of decreased host susceptibility drives a stable relationship between ultrasmall parasite TM7x and its bacterial host

2018 ◽  
Vol 115 (48) ◽  
pp. 12277-12282 ◽  
Author(s):  
Batbileg Bor ◽  
Jeffrey S. McLean ◽  
Kevin R. Foster ◽  
Lujia Cen ◽  
Thao T. To ◽  
...  
Keyword(s):  
Host Cell ◽  
Rapid Evolution ◽  
Host Population ◽  
Host Cells ◽  
Host Susceptibility ◽  
Bacterial Host ◽  
Narrow Host Range ◽  
Stable Relationship ◽  
Candidate Phyla Radiation

Around one-quarter of bacterial diversity comprises a single radiation with reduced genomes, known collectively as the Candidate Phyla Radiation. Recently, we coisolated TM7x, an ultrasmall strain of the Candidate Phyla Radiation phylum Saccharibacteria, with its bacterial host Actinomyces odontolyticus strain XH001 from human oral cavity and stably maintained as a coculture. Our current work demonstrates that within the coculture, TM7x cells establish a long-term parasitic association with host cells by infecting only a subset of the population, which stay viable yet exhibit severely inhibited cell division. In contrast, exposure of a naïve A. odontolyticus isolate, XH001n, to TM7x cells leads to high numbers of TM7x cells binding to each host cell, massive host cell death, and a host population crash. However, further passaging reveals that XH001n becomes less susceptible to TM7x over time and enters a long-term stable relationship similar to that of XH001. We show that this reduced susceptibility is driven by rapid host evolution that, in contrast to many forms of phage resistance, offers only partial protection. The result is a stalemate where infected hosts cannot shed their parasites; nevertheless, parasite load is sufficiently low that the host population persists. Finally, we show that TM7x can infect and form stable long-term relationships with other species in a single clade of Actinomyces, displaying a narrow host range. This system serves as a model to understand how parasitic bacteria with reduced genomes such as those of the Candidate Phyla Radiation have persisted with their hosts and ultimately expanded in their diversity.

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