Reproducible Nonlinear Population Dynamics and Critical Points During Replicative Competitions of RNA Virus Quasispecies

Quer, Josep; Huerta, Ramón; Novella, Isabel S.; Tsimring, Lev S.; Domingo, Esteban; Holland, John J.

doi:10.1006/jmbi.1996.0654

Cited by 67 publications

(62 citation statements)

References 30 publications

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“…Therefore, in contrast to other mutants of VSV employed in a previous study (MARM-D, -G, and -H) that exhibited stochastic displacements of either the wt or the MARM in the course of passages (6), MARM-C was consistently displaced in a nonlinear manner by wt parental virus (29). However, isolation of MARM-C and wt prior to extinction of the latter showed that, as in previous experiments, both populations gained fitness.…”

contrasting

confidence: 43%

“…BHK-21 cells were grown as cell monolayers in Eagle minimum essential medium (MEM) containing heat-inactivated (60°C, 30 min) bovine calf serum. A wt population of VSV Mudd-Summer strain, Indiana serotype, and a genetically marked MAb-resistant mutant (MARM-C [29]) were used. The competing wt quasispecies population was previously replicated exclusively on BHK-21 cells, and it was stored frozen at Ϫ85°C.…”

Section: Methodsmentioning

confidence: 99%

“…The words of the Red Queen in Lewis Carroll's Through the Looking Glass are "it takes all the running you can do to keep in the same place." Analysis of competing populations showed that both the winners and the losers increased in fitness, but the winners did so at a higher level than the losers (6,29).…”

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confidence: 98%

“…In another series of independent competitions between a wild-type (wt) VSV and a neutral monoclonal antibody (MAb)-resistant mutant, termed MARM-C VSV, it was observed that the relative ratio between competitors remained constant for 8 to 10 passages, but after that the wt always displaced MARM-C, and the critical displacement transition occurred anywhere between passages 30 and 100 (29). Therefore, in contrast to other mutants of VSV employed in a previous study (MARM-D, -G, and -H) that exhibited stochastic displacements of either the wt or the MARM in the course of passages (6), MARM-C was consistently displaced in a nonlinear manner by wt parental virus (29).…”

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confidence: 99%

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Contingent Neutrality in Competing Viral Populations

Quer

Hershey

Domingo

et al. 2001

J Virol

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The replicative fitness of a genetically marked (MARM-C) population of vesicular stomatitis virus was examined in competition assays in BHK-21 cells. In standard fitness assays involving up to eight competition passages of the mixed populations, MARM-C competes equally with the wild type (wt), but very prolonged competitions always led to the wt gaining dominance over MARM-C in a very slowed, nonlinear manner (J. Quer et al., J. Mol. Biol. 264: [465][466][467][468][469][470][471] 1996). In the present study we show that a number of quite unrelated environmental perturbations, which decreased virus replication during competitions, all led to an accelerated dominance of the wt over MARM-C. These perturbations were (i) the presence of added (or endogenously generated) defective interfering particles, (ii) the presence of the chemical mutagen 5-fluorouracil (5-FU), or (iii) an increase in temperature to 40.5°C. Thus, the "neutral fitness" of the MARM-C population is contingent. We have determined the entire genomic consensus sequence of MARM-C and have identified only six mutations. Clearly, some or all of these mutations allowed the MARM-C quasispecies population to compete equally with wt in a defined constant host environment, but the period of neutrality was shortened when the environment was perturbed during competitions. Interestingly, when four passages of each population were carried out independently in the presence of 5-FU (but in the absence of competition), no significant differences were detected in the fitness changes of wt and MARM-C, nor was there a difference in their subsequent abilities to compete with each other in a standard fitness assay. We propose a model for this contingent neutrality. The conditions employed to generate the MARM-C quasispecies population selected a small number of mutations in the consensus sequence. It appears that the MARM-C quasispecies population has moved into a segment of sequence space in which the average fitness value is neutral but, under environmental stress, beneficial mutations cannot be generated rapidly enough to compete with those being generated concurrently by competing wt virus quasispecies populations.

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 98%

mentioning

confidence: 99%

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Contingent Neutrality in Competing Viral Populations

Quer

Hershey

Domingo

et al. 2001

J Virol

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“…These models also allow for dynamics at higher mutation incidence where all one-step mutations are produced in the population in one generation, and double mutants, triple mutants, etc., may also arise. This generally yields more deterministic dynamics as the population searches sequence space more systematically (Quer et al 1996).…”

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confidence: 99%

Mutational Effects and Population Dynamics During Viral Adaptation Challenge Current Models

Joyce²,

2011

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Adaptation in haploid organisms has been extensively modeled but little tested. Using a microvirid bacteriophage (ID11), we conducted serial passage adaptations at two bottleneck sizes (10 4 and 10 6 ), followed by fitness assays and whole-genome sequencing of 631 individual isolates. Extensive genetic variation was observed including 22 beneficial, several nearly neutral, and several deleterious mutations. In the three large bottleneck lines, up to eight different haplotypes were observed in samples of 23 genomes from the final time point. The small bottleneck lines were less diverse. The small bottleneck lines appeared to operate near the transition between isolated selective sweeps and conditions of complex dynamics (e.g., clonal interference). The large bottleneck lines exhibited extensive interference and less stochasticity, with multiple beneficial mutations establishing on a variety of backgrounds. Several leapfrog events occurred. The distribution of first-step adaptive mutations differed significantly from the distribution of second-steps, and a surprisingly large number of second-step beneficial mutations were observed on a highly fit first-step background. Furthermore, few first-step mutations appeared as second-steps and second-steps had substantially smaller selection coefficients. Collectively, the results indicate that the fitness landscape falls between the extremes of smooth and fully uncorrelated, violating the assumptions of many current mutational landscape models.

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Evolutionary trajectory of fishPiscine novirhabdovirus(=Viral Hemorrhagic Septicemia Virus) across its Laurentian Great Lakes history: Spatial and temporal diversification

Stepien

Niner

2020

Ecology and Evolution

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Piscine novirhabdovirus = Viral Hemorrhagic Septicemia Virus (VHSV) first appeared in the Laurentian Great Lakes with large outbreaks from 2005 to 2006, as a new and novel RNA rhabdovirus subgenogroup (IVb) that killed >30 fish species. Interlude periods punctuated smaller more localized outbreaks in 2007, 2010, and 2017, although some fishes tested positive in the intervals. There have not been reports of outbreaks or positives from 2018, 2019, or 2020. Here, we employ a combined population genetics and phylogenetic approach to evaluate spatial and temporal evolutionary trajectory on its G‐gene sequence variation, in comparison with whole‐genome sequences (11,083 bp) from a subset of 44 individual isolates (including 40 newly sequenced ones). Our results show that IVb (N = 184 individual fish isolates) diversified into 36 G‐gene haplotypes from 2003 to 2017, stemming from two originals (“a” and “b”). G‐gene haplotypes “a” and “b” differed by just one synonymous single‐nucleotide polymorphism (SNP) substitution, remained the most abundant until 2011, then disappeared. Group “a” descendants (14 haplotypes) remained most prevalent in the Upper and Central Great Lakes, with eight (51%) having nonsynonymous substitutions. Group “b” descendants primarily have occurred in the Lower Great Lakes, including 22 haplotypes, of which 15 (68%) contained nonsynonymous changes. Evolutionary patterns of the whole‐genome sequences (which had 34 haplotypes among 44 isolates) appear congruent with those from the G‐gene. Virus populations significantly diverged among the Upper, Central, and Lower Great Lakes, diversifying over time. Spatial divergence was apparent in the overall patterns of nucleotide substitutions, while amino acid changes increased temporally. VHSV‐IVb thus significantly differentiated across its less than two decades in the Great Lakes, accompanied by declining outbreaks and virulence. Continuing diversification likely allowed the virus to persist at low levels in resident fish populations, and may facilitate its potential for further and future spread to new habitats and nonacclimated hosts.

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Reproducible Nonlinear Population Dynamics and Critical Points During Replicative Competitions of RNA Virus Quasispecies

Cited by 67 publications

References 30 publications

Contingent Neutrality in Competing Viral Populations

Contingent Neutrality in Competing Viral Populations

Mutational Effects and Population Dynamics During Viral Adaptation Challenge Current Models

Evolutionary trajectory of fishPiscine novirhabdovirus(=Viral Hemorrhagic Septicemia Virus) across its Laurentian Great Lakes history: Spatial and temporal diversification

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