Search results for "mutation."
showing 10 items of 2808 documents
Exploring new roles for the rpoS gene in the survival and virulence of the fire blight pathogen Erwinia amylovora
2014
Erwinia amylovora causes fire blight in economically important plants of the family Rosaceae. This bacterial pathogen spends part of its life cycle coping with starvation and other fluctuating environmental conditions. In many Gram-negative bacteria, starvation and other stress responses are regulated by the sigma factor RpoS. We obtained an E. amylovora rpoS mutant to explore the role of this gene in starvation responses and its potential implication in other processes not yet studied in this pathogen. Results showed that E. amylovora needs rpoS to develop normal starvation survival and viable but nonculturable (VBNC) responses. Furthermore, this gene contributed to stationary phase cross-…
A Grid Enabled Parallel Hybrid Genetic Algorithm for SPN
2004
This paper presents a combination of a parallel Genetic Algorithm (GA) and a local search methodology for the Steiner Problem in Networks (SPN). Several previous papers have proposed the adoption of GAs and others metaheuristics to solve the SPN demonstrating the validity of their approaches. This work differs from them for two main reasons: the dimension and the features of the networks adopted in the experiments and the aim from which it has been originated. The reason that aimed this work was namely to assess deterministic and computationally inexpensive algorithms which can be used in practical engineering applications, such as the multicast transmission in the Internet. The large dimen…
Diminishing Returns of Population Size in the Rate of RNA Virus Adaptation
2000
ABSTRACT Whenever an asexual viral population evolves by adapting to new environmental conditions, beneficial mutations, the ultimate cause of adaptation, are randomly produced and then fixed in the population. The larger the population size and the higher the mutation rate, the more beneficial mutations can be produced per unit time. With the usually high mutation rate of RNA viruses and in a large enough population, several beneficial mutations could arise at the same time but in different genetic backgrounds, and if the virus is asexual, they will never be brought together through recombination. Thus, the best of these genotypes must outcompete each other on their way to fixation. This c…
Experimental Evolution in Viruses
2011
Experiments in which evolution takes place in real time can help us establish cause–effect relationships that are difficult to infer from the analysis of natural populations. The simplicity, rapid evolution and biomedical relevance of viruses make them a particularly interesting model system for experimental evolution. Bacterial, animal and plant viruses can be passaged under a variety of conditions, either in simple cell culture systems or in vivo to test population biology hypotheses, study the genetic basis of evolution, or predict evolutionary change in nature. Experimental evolution is a conceptually simple and flexible tool which allows us to address issues ranging from the molecular …
Nucleoside Analogue Mutagenesis of a Single-Stranded DNA Virus: Evolution and Resistance
2012
ABSTRACT 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 conce…
The effect of genetic robustness on evolvability in digital organisms
2008
Abstract Background Recent work has revealed that many biological systems keep functioning in the face of mutations and therefore can be considered genetically robust. However, several issues related to robustness remain poorly understood, such as its implications for evolvability (the ability to produce adaptive evolutionary innovations). Results Here, we use the Avida digital evolution platform to explore the effects of genetic robustness on evolvability. First, we obtained digital organisms with varying levels of robustness by evolving them under combinations of mutation rates and population sizes previously shown to select for different levels of robustness. Then, we assessed the abilit…
Delayed lysis confers resistance to the nucleoside analogue 5-fluorouracil and alleviates mutation accumulation in the single-stranded DNA bacterioph…
2014
ABSTRACT Rates of spontaneous mutation determine viral fitness and adaptability. In RNA viruses, treatment with mutagenic nucleoside analogues selects for polymerase variants with increased fidelity, showing that viral mutation rates can be adjusted in response to imposed selective pressures. However, this type of resistance is not possible in viruses that do not encode their own polymerases, such as single-stranded DNA viruses. We previously showed that serial passaging of bacteriophage ϕX174 in the presence of the nucleoside analogue 5-fluorouracil (5-FU) favored substitutions in the lysis protein E (P. Domingo-Calap, M. Pereira-Gomez, and R. Sanjuán, J. Virol. 86: 9640–9646, 2012, doi:10…
Changes in protein domains outside the catalytic site of the bacteriophage Qβ replicase reduce the mutagenic effect of 5-azacytidine.
2014
ABSTRACT The high genetic heterogeneity and great adaptability of RNA viruses are ultimately caused by the low replication fidelity of their polymerases. However, single amino acid substitutions that modify replication fidelity can evolve in response to mutagenic treatments with nucleoside analogues. Here, we investigated how two independent mutants of the bacteriophage Qβ replicase (Thr210Ala and Tyr410His) reduce sensitivity to the nucleoside analogue 5-azacytidine (AZC). Despite being located outside the catalytic site, both mutants reduced the mutation frequency in the presence of the drug. However, they did not modify the type of AZC-induced substitutions, which was mediated mainly by …
Distribution of Fitness Effects Caused by Single-Nucleotide Substitutions in Bacteriophage f1
2010
Empirical knowledge of the fitness effects of mutations is important for understanding many evolutionary processes, yet this knowledge is often hampered by several sources of measurement error and bias. Most of these problems can be solved using site-directed mutagenesis to engineer single mutations, an approach particularly suited for viruses due to their small genomes. Here, we used this technique to measure the fitness effect of 100 single-nucleotide substitutions in the bacteriophage f1, a filamentous single-strand DNA virus. We found that approximately one-fifth of all mutations are lethal. Viable ones reduced fitness by 11% on average and were accurately described by a log-normal dist…
Cancer growth dynamics: stochastic models and noise induced effects
2009
In the framework of the Michaelis‐Menten (MM) reaction kinetics, we analyze the cancer growth dynamics in the presence of the immune response. We found the coexistence of noise enhanced stability (NES) and resonant activation (RA) phenomena which act in an opposite way with respect to the extinction of the tumor. The role of the stochastic resonance (SR) in the case of weak cancer therapy has been analyzed. The evolutionary dynamics of a system of cancerous cells in a model of chronic myeloid leukemia (CML) is investigated by a Monte Carlo approach. We analyzed the effects of a targeted therapy on the evolutionary dynamics of normal, first‐mutant and cancerous cell populations. We show how …