Following the very initial growth of biological RNA viral clones

2005 ◽  
Vol 86 (2) ◽  
pp. 435-443 ◽  
Author(s):  
José M. Cuevas ◽  
Andrés Moya ◽  
Rafael Sanjuán

Due to their extremely high genetic diversity, which is a direct consequence of high mutation rates, RNA viruses are often described as molecular quasispecies. According to this theory, RNA virus populations cannot be understood in terms of individual viral clones, as they are clouds of interconnected mutants, but this prediction has not yet been demonstrated experimentally. The goal of this study was to determine the fitness of individual clones sampled from a given RNA virus population, a necessary previous step to test the above prediction. To do so, limiting dilutions of a vesicular stomatitis virus population were employed to isolate single viral clones and their initial growth dynamics were followed, corresponding to the release of the first few hundred viral particles. This technique is useful for estimating basic fitness parameters, such as intracellular growth rate, viral yield per cell, rate at which cells are infected and time spent in cell-to-cell transmission. A combination of these parameters allows estimation of the fitness of individual clones, which seems to be determined mainly by their ability to complete infection cycles more quickly. Interestingly, fitness was systematically higher for initial clones than for their derived populations. In addition to environmental changes, such as cellular defence mechanisms, these differences are attributable to high RNA virus mutation rates.

2012 ◽  
Vol 8 (9) ◽  
pp. e1002897 ◽  
Author(s):  
Naomi L. Forrester ◽  
Mathilde Guerbois ◽  
Robert L. Seymour ◽  
Heidi Spratt ◽  
Scott C. Weaver

2001 ◽  
Vol 77 (1) ◽  
pp. 53-60 ◽  
Author(s):  
JAMES D. FRY

High rates of mildly deleterious mutation could cause the extinction of small populations, reduce neutral genetic variation and provide an evolutionary advantage for sex. In the first attempts to estimate the rate of mildly deleterious mutation, Mukai and Ohnishi allowed spontaneous mutations to accumulate on D. melanogaster second chromosomes shielded from recombination and selection. Viability of the shielded chromosomes appeared to decline rapidly, implying a deleterious mutation rate on the order of one per zygote per generation. These results have been challenged, however; at issue is whether Mukai and Ohnishi may have confounded viability declines caused by mutation with declines resulting from environmental changes or other extraneous factors. Here, using a method not sensitive to non-mutational viability changes, I reanalyse the previous mutation-accumulation (MA) experiments, and report the results of a new one. I show that in each of four experiments, including Mukai's two experiments, viability declines due to mildly deleterious mutations were rapid. The results give no support for the view that Mukai overestimated the declines. Although there is substantial variation in estimates of genomic mutation rates from the experiments, this variation is probably due to some combination of sampling error, strain differences and differences in assay conditions, rather than to failure to distinguish mutational and non-mutational viability changes.


2005 ◽  
Vol 16 (01) ◽  
pp. 85-97 ◽  
Author(s):  
DOKYOON KIM ◽  
WONPYONG GILL

The crossing time through fitness barrier in a symmetric multiplicative landscape is systematically calculated for various mutation rates, fitness parameters, and sequence lengths by using a computer simulation. It is found that the crossing time scales as a power law in the mutation rate and the fitness parameter. It is also found that the crossing time increases exponentially as the sequence length increases. We have obtained the approximate formula, which decribes the asymptotic behavior of the crossing time in the long-crossing-time region, and the improved approximate formula with the correction factor, which nicely fit computer simulation results even below the long-crossing-time region. From the comparison between the approximate formula in the multiplicative landscape and the approximate formula in the sharply-peaked landscape, it is found that both landscapes have the same scaling effect of fitness parameter and mutation rate on the crossing time in the long-crossing-time region.


MycoKeys ◽  
2020 ◽  
Vol 65 ◽  
pp. 1-24
Author(s):  
Jaime Gasca-Pineda ◽  
Patricia Velez ◽  
Tsuyoshi Hosoya

During the Last Glacial Maximum (LGM), drastic environmental changes modified the topology of the Japanese Archipelago, impacting species distributions. An example is Fagus crenata, which has a present continuous distribution throughout Japan. However, by the end of the LGM it was restricted to southern refugia. Similarly, Dasyscyphella longistipitata (Leotiomycetes, Helotiales, Lachnaceae) occurs strictly on cupules of F. crenata, sharing currently an identical distribution. As the effects of the LGM remain poorly understood for saprobiotic microfungal species, herein we identified past structuring forces that shaped the current genetic diversity within D. longistipitata in relation to its host using a phylogeographic approach. We inferred present and past potential distributions through species distribution modeling, identifying environmental suitability areas in mid-southern Japan from which subsequent colonizations occurred. Our findings suggest that current high genetic diversity and lack of genetic structure within D. longistipitata are the result of recent multiple re-colonization events after the LGM.


2021 ◽  
Vol 58 (4) ◽  
Author(s):  
Rosvita Sitar ◽  
Tanja Švara ◽  
Aleksandra Grilc Fajfar ◽  
Sabina Šturm ◽  
Marko Cvetko ◽  
...  

Abstract: Viral encephalopathy and retinopathy (VER) is considered a serious disease of several marine fish species, caused by RNA virus belonging to the family Nodaviridae, genus Betanodavirus. The disease is spread almost worldwide and causes significant losses among diseased fish. It is characterised by vacuolation of the central nervous system and the retina. In July 2018, behavioural abnormalities i.e. altered swimming, swirling and vertical floating as well as lethargy and anorexia were observed in farmed sea bass (Dicentrarchus labrax) in the Gulf of Piran (Slovenia), associated with significant mortality. The disease initially occurred in juvenile sea bass, but later market-sized fish also became affected. Diseased fish displayed ocular opacity and multifocal skin ulceration on the head. Emaciation in some fish was also evident. Histopathology revealed characteristic vacuolation in the brain and retina. Performing a RT-PCR and RT-qPCR techniques, we have identified and confirmed the presence of betanodavirus nucleic acid in ocular and brain tissues. In addition, concentrations of the causative agent of VER in spleen and kidney did result in significantly higher viral yield than expected. Phylogenetic analysis showed that Slovenian isolate belongs to RGNNV species of betanodaviruses. Based on the clinical signs, gross and typical microscopic lesions and results of molecular analyses, we can conclude that farmed sea bass from the Gulf of Piran were affected with VER. To the best of our knowledge, this is the first report of VER in Slovenia.Key words: viral encephalopathy and retinopathy; betanodavirus; sea bass; histopathology; RT-qPCR PRVI IZBRUH VIRUSNE ENCEFALOPATIJE IN RETINOPATIJE PRI GOJENIH BRANCINIH (Dicentrarchus labrax) V SLOVENIJI Izvleček: Virusna encefalopatija in retinopatija (VER) je nevarna bolezen številnih vrst morskih rib, ki jo povzroča nevrotropni RNA virus iz družine Nodaviridae, rod Betanodavirus. Bolezen je razširjena skoraj po vsem svetu in povzroča visok pogin okuženih rib. Zanjo so značilne vakuole v centralnem živčnem sistemu in retini. Konec julija 2018 so v ribogojnici v Piranskem zalivu pri brancinih opazili nepravilno plavanje, vrtenje in postavljanje v vertikalno smer ter letargijo in neješčnost, brancini so množično poginjali. Bolezen se je najprej pojavila pri mladicah, nato tudi pri konzumnih kategorijah brancinov. Obolele ribe so imele sivo-motna očesna zrkla ter multifokalne kožne razjede na glavi, posamezne so bile shujšane. S histopatološko preiskavo smo ugotovili značilne vakuole v možganih in retini. Z molekularnima metodama RT-PCR in RT-qPCR smo potrdili prisotnost nukleinske kisline betanodavirusa v očesnem zrklu in možganih. Koncentracije virusa, ki so bile signifikantno višje od pričakovanih, smo ugotovili tudi v vranici in ledvicah. Na podlagi kliničnih znakov, makroskopskih in tipičnih histopatoloških sprememb ter rezultatov molekularnih preiskav lahko zaključimo, da so gojeni brancini v ribogojnici v Piranskem zalivu zboleli za VER. Opisani izbruh je prvi potrjeni primer te bolezni v Sloveniji.Ključne besede: virusna encefalopatija in retinopatija; betanodavirus; brancin; histopatologija; RT-qPCR


2021 ◽  
Vol 9 (5) ◽  
pp. 591-597
Author(s):  
Bramhadev Pattnaik ◽  
◽  
Kuralayanapalya Puttahonnappa Suresh ◽  
Rajangam Sridevi ◽  
Mahendra P. Yadav ◽  
...  

Since the identification of the SARS-CoV-2, genus Beta- Coronavirus, in January 2020, the virus quickly spread in less than 3 months to all continents with a susceptible human population of about a 7.9billion, and still in active circulation. In the process, it has accumulated mutations leading to genetic diversity. Regular emergence of variants of concern/significance in different ecology shows genetic heterogeneity in the base population of SARS-CoV-2 that is continuously expanding with the passage of the virus in the vast susceptible human population. Natural selection of mutant occurs frequently in a positive sense (+) single-stranded (ss) RNA virus upon replication in the host. The Pressure of sub-optimal levels of virus-neutralizing antibodies and also innate immunity influence the process of genetic/ antigenic selection. The fittest of the mutants, that could be more than one, propagate and emerge as variants. The existence of different lineages, clades, and strains, as well as genetic heterogeneity of plaque purified virus population, justifies SARS-CoV-2 as ‘Quasispecies’ that refers to swarms of mutant sequences generated during replication of the viral genome, and all mutant sequences may not lead to virion. Viruses having a quasispecies nature may end up with progressive antigenic changes leading to antigenic plurality that is driven by ecology, and this phenomenon challenges vaccination-based control programs.


Viruses ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2535
Author(s):  
Mirna Jurković ◽  
Anamarija Slović ◽  
Dubravko Forčić ◽  
Jelena Ivančić-Jelečki ◽  
Tanja Košutić-Gulija ◽  
...  

Frequent mumps outbreaks in vaccinated populations and the occurrence of neurological complications (e.g., aseptic meningitis or encephalitis) in patients with mumps indicate the need for the development of more efficient vaccines as well as specific antiviral therapies. RNA viruses are genetically highly heterogeneous populations that exist on the edge of an error threshold, such that additional increases in mutational burden can lead to extinction of the virus population. Deliberate modulation of their natural mutation rate is being exploited as an antiviral strategy and a possibility for rational vaccine design. The aim of this study was to examine the ability of ribavirin, a broad-spectrum antiviral agent, to introduce mutations in the mumps virus (MuV) genome and to investigate if resistance develops during long-term in vitro exposure to ribavirin. An increase in MuV population heterogeneity in the presence of ribavirin has been observed after one passage in cell culture, as well as a bias toward C-to-U and G-to-A transitions, which have previously been defined as ribavirin-related. At higher ribavirin concentration, MuV loses its infectivity during serial passaging and does not recover. At low ribavirin concentration, serial passaging leads to a more significant increase in population diversity and a stronger bias towards ribavirin-related transitions, independently of viral strain or cell culture. In these conditions, the virus retains its initial growth capacity, without development of resistance at a whole-virus population level.


Pathogens ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 80 ◽  
Author(s):  
Pilar Somovilla ◽  
Susanna Manrubia ◽  
Ester Lázaro

The rate of change in selective pressures is one of the main factors that determines the likelihood that populations can adapt to stress conditions. Generally, the reduction in the population size that accompanies abrupt environmental changes makes it difficult to generate and select adaptive mutations. However, in systems with high genetic diversity, as happens in RNA viruses, mutations with beneficial effects under new conditions can already be present in the population, facilitating adaptation. In this work, we have propagated an RNA bacteriophage (Qβ) at temperatures higher than the optimum, following different patterns of change. We have determined the fitness values and the consensus sequences of all lineages throughout the evolutionary process in order to establish correspondences between fitness variations and adaptive pathways. Our results show that populations subjected to a sudden temperature change gain fitness and fix mutations faster than those subjected to gradual changes, differing also in the particular selected mutations. The life-history of populations prior to the environmental change has great importance in the dynamics of adaptation. The conclusion is that in the bacteriophage Qβ, the standing genetic diversity together with the rate of temperature change determine both the rapidity of adaptation and the followed evolutionary pathways.


2020 ◽  
Author(s):  
Mayara Delagnelo Medeiros ◽  
Daniel Galiano ◽  
Bruno Busnello Kubiak ◽  
Paula Angélica Roratto ◽  
Thales Renato Ochotorena de Freitas

Abstract Endemic, small range species are susceptible to environmental changes and landscape modification. Understanding genetic diversity and distributional patterns is important for implementation of effective conservation measures. In this context, genetic diversity was evaluated to update the conservation status of an endemic tuco-tuco, Ctenomys ibicuiensis. Phylogeographic and population genetic analyses of mitochondrial DNA and microsatellite loci were carried out using 46 individuals sampled across the species’ distribution. Ctenomys ibicuiensis presented moderate to high genetic diversity and highly structured populations with low levels of gene flow and isolation by distance. Anthropogenic landscape changes threaten this restricted-range tuco-tuco. Considering its limited geographic distribution and highly structured populations with low gene flow, we consider C. ibicuiensis to be at significant risk of extinction.


2009 ◽  
Vol 5 (3) ◽  
pp. 394-396 ◽  
Author(s):  
Rafael Sanjuán ◽  
Patricia Agudelo-Romero ◽  
Santiago F. Elena

It is generally accepted that mutation rates of RNA viruses are inherently high due to the lack of proofreading mechanisms. However, direct estimates of mutation rate are surprisingly scarce, in particular for plant viruses. Here, based on the analysis of in vivo mutation frequencies in tobacco etch virus , we calculate an upper-bound mutation rate estimation of 3×10 −5 per site and per round of replication; a value which turns out to be undistinguishable from the methodological error. Nonetheless, the value is barely on the lower side of the range accepted for RNA viruses, although in good agreement with the only direct estimate obtained for other plant viruses. These observations suggest that, perhaps, differences in the selective pressures operating during plant virus evolution may have driven their mutation rates towards values lower than those characteristic of other RNA viruses infecting bacteria or animals.


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