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S F Elena

Publications and source records attributed to S F Elena.

At least 19 recordsLinked to original sources
PubMed2000

The evolution of RNA viruses: A population genetics view.

RNA viruses are excellent experimental models for studying evolution under the theoretical framework of population genetics. For a proper justification of this thesis we have introduced some properties of RNA viruses that are relevant for studying evolution. On the other hand, population genetics is a reductionistic theory of evolution. It does not consider or make simplistic assumptions on the transformation laws within and between genotypic and phenotypic spaces. However, such laws are minimized in the case of RNA viruses because the phenotypic space maps onto the genotypic space in a much more linear way than on higher DNA-based organisms. Under experimental conditions, we have tested the role of deleterious and beneficial mutations in the degree of adaptation of vesicular stomatitis virus (VSV), a nonsegmented virus of negative strand. We also have studied how effective population size, initial genetic variability in populations, and environmental heterogeneity shapes the impact of mutations in the evolution of vesicular stomatitis virus. Finally, in an integrative attempt, we discuss pros and cons of the quasispecies theory compared with classic population genetics models for haploid organisms to explain the evolution of RNA viruses.

Biological Evolution↗
PubMed2000

The two faces of mutation: extinction and adaptation in RNA viruses.

From a population standpoint, two main features characterize the replication of RNA viruses and viruses that use RNA as a replicative intermediate: high genetic variability, and enormous fluctuations in population size. Their genetic variability mainly reflects a lack of the proof-reading and post-replicative error correction mechanisms that operate during cellular DNA replication, but recombination and segment exchange can also play an important role. Viral population size can change tremendously as a consequence of transmission between hosts or between different tissues within an infected host. A new infection can be initiated with very few particles that subsequently expand many trillion-fold. Repeated bottleneck events can lead to drastic fitness losses or even to viral extinction, whereas continuously large population sizes result in fitness gains and adaptation. Here we review experimental evidence for the effects of mutation, selection, and genetic drift on the adaptation and extinction of RNA viruses.

Adaptation, Physiological↗
PubMed2000

Diminishing returns of population size in the rate of RNA virus adaptation.

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 competition among beneficial mutations has the effect of slowing the overall rate of adaptation. This phenomenon is known as clonal interference. Clonal interference predicts a speed limit for adaptation as the population size increases. In the present report, by varying the size of evolving vesicular stomatitis virus populations, we found evidence clearly demonstrating this speed limit and thus indicating that clonal interference might be an important factor modulating the rate of adaptation to an in vitro cell system. Several evolutionary and epidemiological implications of the clonal interference model applied to RNA viruses are discussed.

Adaptation, Physiological↗
PubMed2000

Effect of deleterious mutation-accumulation on the fitness of RNA bacteriophage MS2.

RNA viruses show the highest mutation rate in nature. It has been extensively demonstrated that, in the absence of purifying selection, RNA viruses accumulate deleterious mutations at a high rate. However, the parameters describing this accumulation are, in general, poorly understood. The present study reports evidences for fitness declines by the accumulation of deleterious mutations in the bacteriophage MS2. We estimated the rate of fitness decline to be as high as 16% per bottleneck transfer. In addition, our results agree with an additive model of fitness effects.

Base Sequence↗
PubMed1999

Clonal interference and the evolution of RNA viruses.

In asexual populations, beneficial mutations that occur in different lineages compete with one another. This phenomenon, known as clonal interference, ensures that those beneficial mutations that do achieve fixation are of large effect. Clonal interference also increases the time between fixations, thereby slowing the adaptation of asexual populations. The effects of clonal interference were measured in the asexual RNA virus vesicular stomatitis virus; rates and average effects of beneficial mutations were quantified.

Adaptation, Physiological↗
PubMed1999

Little evidence for synergism among deleterious mutations in a nonsegmented RNA virus.

Several models have been proposed to account for the segmentation of RNA viruses. One of the best known models suggests that segmentation, and mixing of segments during coinfections, is a way to eliminate deleterious mutations from the genome. However, for validity, this model requires that deleterious mutations interact in a synergistic way. That is, two mutations together should have a more deleterious effect than the result of adding their individual effects. Here I present evidence that deleterious mutations in foot-and-mouth disease virus produce a decline in fitness but that the relationship between the number of mutations fixed and the magnitude of fitness decline is compatible mainly with a nonsynergistic model. However, the statistical uncertainties associated with the data still give some room for the existence of very weak synergistic epistasis.

Aphthovirus↗
PubMed1998

Distribution of fitness effects caused by random insertion mutations in Escherichia coli.

Very little is known about the distribution of mutational effects on organismal fitness, despite the fundamental importance of this information for the study of evolution. This lack of information reflects the fact that it is generally difficult to quantify the dynamic effects of mutation and natural selection using only static distributions of allele frequencies. In this study, we took a direct approach to measuring the effects of mutations on fitness. We used transposon-mutagenesis to create 226 mutant clones of Escherichia coli. Each mutant clone carried a single random insertion of a derivative of Tn10. All 226 mutants were independently derived from the same progenitor clone, which was obtained from a population that had evolved in a constant laboratory environment for 10,000 generations. We then performed competition experiments to measure the effect of each mutation on fitness relative to a common competitor. At least 80% of the mutations had a significant negative effect on fitness, whereas none of the mutations had a significant positive effect. The mutations reduced fitness by about 3%, on average, but the distribution of fitness effects was highly skewed and had a long, flat tail. A compound distribution, which includes both gamma and uniform components, provided an excellent fit to the observed fitness values.

Biological Evolution↗
PubMed1997

Test of synergistic interactions among deleterious mutations in bacteria.

Identifying the forces responsible for the origin and maintenance of sexuality remains one of the greatest unsolved problems in biology. The mutational deterministic hypothesis postulates that sex is an adaptation that allows deleterious mutations to be purged from the genome; it requires synergistic interactions, which means that two mutations would be more harmful together than expected from their separate effects. We generated 225 genotypes of Escherichia coli carrying one, two or three successive mutations and measured their fitness relative to an unmutated competitor. The relationship between mutation number and average fitness is nearly log-linear. We also constructed 27 recombinant genotypes having pairs of mutations whose separate and combined effects on fitness were determined. Several pairs exhibit significant interactions for fitness, but they are antagonistic as often as they are synergistic. These results do not support the mutational deterministic hypothesis for the evolution of sex.

Directed Molecular Evolution↗
PubMed1997

Is group selection a factor modulating the virulence of RNA viruses?

RNA viruses consist of populations of extremely high genetic heterogeneity called quasispecies. Based on theoretical considerations, it has been suggested that the unit of selection in such complex genetic populations is not the single viral particle but a set of genetically related particles which form the quasispecies. In the present study we carried out a set of experiments with the vesicular stomatitis virus (VSV) dealing with the evolution of life-history characters under selection acting at two factors either in the same or in opposite directions. The two factors at which selective pressure is applied are the individual and the group. We show evidence that group selection modulates the virulence of VSV populations, in opposition to an unlimited increase in virulence by competitive optimization promoted by individual selection. The results are of relevance for understanding the evolution of parasite virulence.

Genetics, Population↗
PubMed1996

Repeated transfer of small RNA virus populations leading to balanced fitness with infrequent stochastic drift.

The population dynamics of RNA viruses have an important influence on fitness variation and, in consequence, on the adaptative potential and virulence of this ubiquitous group of pathogens. Earlier work with vesicular stomatitis virus showed that large population transfers were reproducibly associated with fitness increases, whereas repeated transfers from plaque to plaque (genetic bottlenecks) lead to losses in fitness. We demonstrate here that repeated five-plaque to five-plaque passage series yield long-term fitness stability, except for occasional stochastic fitness jumps. Repeated five-plaque passages regularly alternating with two consecutive large population transmissions did not cause fitness losses, but did limit the size of fitness gains that would otherwise have occurred. These results underscore the profound effects of bottleneck transmissions in virus evolution.

Animals↗
PubMed1996

Punctuated evolution caused by selection of rare beneficial mutations.

For more than two decades there has been intense debate over the hypothesis that most morphological evolution occurs during relatively brief episodes of rapid change that punctuate much longer periods of stasis. A clear and unambiguous case of punctuated evolution is presented for cell size in a population of Escherichia coli evolving for 3000 generations in a constant environment. The punctuation is caused by natural selection as rare, beneficial mutations sweep successively through the population. This experiment shows that the most elementary processes in population genetics can give rise to punctuated evolution dynamics.

Alleles↗
PubMed1996

Evolution of fitness in experimental populations of vesicular stomatitis virus.

The evolution of fitness in experimental clonal populations of vesicular stomatitis virus (VSV) has been compared under different genetic (fitness of initial clone) and demographic (population dynamics) regimes. In spite of the high genetic heterogeneity among replicates within experiments, there is a clear effect of population dynamics on the evolution of fitness. Those populations that went through strong periodic bottlenecks showed a decreased fitness in competition experiments with wild type. Conversely, mutant populations that were transferred under the dynamics of continuous population expansions increased their fitness when compared with the same wild type. The magnitude of the observed effect depended on the fitness of the original viral clone. Thus, high fitness clones showed a larger reduction in fitness than low fitness clones under dynamics with included periodic bottleneck. In contrast, the gain in fitness was larger the lower the initial fitness of the viral clone. The quantitative genetic analysis of the trait "fitness" in the resulting populations shows that genetic variation for the trait is positively correlated with the magnitude of the change in the same trait. The results are interpreted in terms of the operation of Muller's ratchet and genetic drift as opposed to the appearance of beneficial mutations.

Adaptation, Physiological↗
PubMed1996

Basic concepts in RNA virus evolution.

A hallmark of RNA genomes is the error-prone nature of their replication and retrotranscription. The major biochemical basis of the limited replication fidelity is the absence of proofreading/repair and postreplicative error correction mechanisms that normally operate during replication of cellular DNA. In spite of this unique feature of RNA replicons, the dynamics of viral populations seems to follow the same basic principles that classical population genetics has established for higher organisms. Here we review recent evidence of the profound effects that genetic bottlenecks have in enhancing the deleterious effects of Muller's ratchet during RNA virus evolution. The validity of the Red Queen hypothesis and of the competitive exclusion principle for RNA viruses are viewed as the expected result of the highly variable and adaptable nature of viral quasispecies. Viral fitness, or ability to replicate infectious progeny, can vary a million-fold within short time intervals. Paradoxically, functional and structural studies suggest extreme limitations to virus variation. Adaptability of RNA viruses appears to be based on the occupation of very narrow portions of sequence space at any given time.

Animals↗
PubMed1996

Large-population passages of vesicular stomatitis virus in interferon-treated cells select variants of only limited resistance.

Vesicular stomatitis virus (VSV) populations were repeatedly passaged in L-929 cells treated with alpha interferon (IFN-alpha) at levels of 25 U/ml. This IFN-alpha concentration induced a 99.9% inhibition of viral yield in standard infections. Analysis of viral fitness (overall replicative ability measured in direct competition with a reference wild-type VSV) after 21 passages in IFN-treated cells showed only a limited increase or no increase in fitness, compared with the greater increase upon parallel passage in cells not treated with IFN-alpha. However, this limited increase in fitness was more pronounced when competition assays were carried out with IFN-alpha-treated cells, suggesting the selection of VSV populations with a low level of resistance to IFN-alpha. Thus, despite the extensively documented capacity of VSV to adapt to changing environments, the antiviral state induced by IFN-alpha imposes adaptive constraints on VSV which are not readily overcome.

Analysis of Variance↗
PubMed1995

Exponential increases of RNA virus fitness during large population transmissions.

The great adaptability shown by RNA viruses is a consequence of their high mutation rates. Here we investigate the kinetics of virus fitness gains during repeated transfers of large virus populations in cell culture. Results always show that fitness increases exponentially. Low fitness clones exhibit regular increases observed as biphasic periods of exponential evolutionary improvement, while neutral clones show monophasic kinetics. These results are significant for RNA virus epidemiology, optimal handling of attenuated live virus vaccines, and routine laboratory procedures.

Animals↗
PubMed1995

Extreme fitness differences in mammalian and insect hosts after continuous replication of vesicular stomatitis virus in sandfly cells.

Continuous, persistent replication of a wild-type strain of vesicular stomatitis virus in cultured sandfly cells for 10 months profoundly decreased virus replicative fitness in mammalian cells and greatly increased fitness in sandfly cells. After persistent infection of sandfly cells, fitness was over 2,000,000-fold greater than that in mammalian cells, indicating extreme selective differences in the environmental conditions provided by insect and mammalian cells. The sandfly-adapted virus also showed extremely low fitness in mouse brain cells (comparable to that in mammalian cell cultures). It also showed an attenuated phenotype, requiring a nearly millionfold higher intracranial dose than that of its parent clone to kill mice. A single passage of this adapted virus in BHK-21 cells at 37 degrees C restored fitness to near neutrality and also restored mouse neurovirulence. These results clearly illustrate the enormous capacity of RNA viruses to adapt to changing selective environments.

Animals↗
PubMed1995

Size of genetic bottlenecks leading to virus fitness loss is determined by mean initial population fitness.

Genetic bottlenecks are important events in the genetic diversification of organisms and colonization of new ecological niches. Repeated bottlenecking of RNA viruses often leads to fitness losses due to the operation of Muller's ratchet. Herein we use vesicular stomatitis virus to determine the transmission population size which leads to fitness decreases of virus populations. Remarkably, the effective size of a genetic bottleneck associated with fitness loss is greater when the fitness of the parental population increases. For example, for starting virus populations with low fitness, population transfers of five-clone-to-five-clone passages resulted in a fitness increase. However, when a parental population with high fitness was transferred, 30-clone-to-30-clone passages were required simply to maintain fitness values.

Animals↗