On the other hand, population genetics is a reductionistic theory of evolution. Quasispecies theory and the behavior of rna viruses core. The rna viruses in the baltimore system are classified as. Another element of the quasispecies which distinguishes it from population genetic models is that the random sampling process of genetic drift is redundant, because the small genomes, large population sizes, and high mutation rates of rna viruses mean that the sequence space i. In the early 1970s the rna bacteriophages, a group of bacterial viruses with rna as genetic material.
Principles and consequences molecular biology intelligence, unit 14. The term quasispecies was introduced by eigen 1996 to describe the. Rna virus simple english wikipedia, the free encyclopedia. Rna viruses, such as human immunodeficiency virus, hepatitis c virus, influenza virus, and poliovirus replicate with very high mutation rates and exhibit very high genetic diversity.
The virus population, often called quasispecies, is shaped by a combination of genetic change and natural selection. An understanding of how such events occur will provide further evidence about whether there are molecular determinants for plaque morphology of rna viruses or. Marine rna virus quasispecies are distributed throughout. Pdf rna viruses, such as human immunodeficiency virus, hepatitis c virus, influenza virus, and poliovirus replicate with very high mutation. Pdf quasispecies theory and the behavior of rna viruses. After a pandemic wave in 2009 following their introduction in the human population, the h1n1pdm09 viruses replaced the previously circulating, prepandemic h1n1 virus and, along with h3n2 viruses, are now responsible for the seasonal influenza type a epidemics. Quasispecies and rna virus evolution by domingo, esteban. Rna viruses, particularly genetically diverse members of the picornavirales, are widespread and abundant in the ocean. Rna viruses are known to replicate by low fidelity polymerases and have high mutation rates whereby the resulting virus population tends to exist as a distribution of mutants. Genetic change is due to both point mutations and recombination events. However, such reformulation of quasispecies theory makes it convergent with conventional population genetic theory in that genetic drift is now allowed to play a role in sequence evolution. Quasispecies structure and dynamics have been studied in detail for virus infecting animals and plants but remain unexplored for those infecting micro.
Studies collected here address connections between theoretical quasispecies and real virus quasispecies, and the biological implications of the quasispecies structure of rna viruses and other simple replicons. There are accumulating reports demonstrating the important role of quasispecies of other rna viruses in the progression of disease. Rna viruses are excellent experimental models for studying evolution under the theoretical framework of population genetics. Frontiers seasonal genetic drift of human influenza a.
Rna virus populations as quasispecies springerlink. For a proper justification of this thesis we have introduced some properties of rna viruses that are relevant for studying evolution. It does not consider or make simplistic assumptions on. So far, the evolutionary potential of influenza viruses has been mainly documented by consensus sequencing data. Pdf quasispecies dynamics of rna viruses miguel angel. Highly variable rna viruses are among the most importanthuman,animal,andplantpathogens,andthepenultimate section covers quasispecies dynamics for three salient human pathogens. Rna viruses exist in their hosts as populations of different but related strains. From quasispecies theory to viral quasispecies mathematical. With rna viruses, the continuous production of mutant viruses inherent to the quasispecies dynamics 14,15 contributes to virus survival 2,57,1517. Evolution of rna genomes from a quasispecies perspective. Hepatitis c virus hcv is an important cause of chronic liver disease worldwide. Quasispecies are no great mystery, and they are usually unimportant when defining a patients genetic version of hepatitis c. The wide host range of the causative pestiviruses may lead to formation of virus reservoirs in other ruminant or wildlife species, presenting a concern for the longterm success of bvd eradication campaigns. Since dmitri ivanovskys 1892 article describing a nonbacterial pathogen infecting tobacco plants, and the discovery of the tobacco mosaic virus by martinus beijerinck in.
Rna viruses are viruses that use rna as their genetic material. The phenomenon of quasispecies within a viral population is also discussed to re. Quasispecies theory describes the evolution of an infinite population of asexual replicators at high mutation rate 1, 2. Crossing such a limit leads to rna virus extinction, a transition that is the basis of an antiviral design termed lethal mutagenesis. Rna viruses exploit all known mechanisms of genetic variation to ensure their survival. Principles and consequences molecular biology intelligence unit esteban domingo, john j. A quasispecies is a large group or cloud of related genotypes that exist in an environment of high mutation rate at stationary state, where a large fraction of offspring are expected to contain one or more mutations relative to. Viral quasispecies evolution microbiology and molecular. In general terms, quasispecies are clouds of genotypes i.
Hcv, the cause of hepatitis c in humans, belongs to the genus hepacivirus within the family of flaviviridae and is also known to exist as quasispecies. The pepper viromes are dominated by geminivirus dnaa followed by a novel carlavirus referred to as pepper virus a. The term quasispecies is often used to refer to populations of rna viruses that contain large numbers of mutants holland et al. The quasispecies model is a description of the process of the darwinian evolution of certain selfreplicating entities within the framework of physical chemistry. A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Quasispecies theory and novel hiv therapeutics based on. Rna viruses, by virtue of their high mutation rates and large population sizes, from complex mutant distributions termed viral quasispecies. The transmission and evolution of hiv1 quasispecies.
Bovine viral diarrhoea virus loses quasispecies diversity. Because dna virus polymerases can have proofreading kornberg 1974, their mutation frequencies can be much lower than those of rna viruses. The nearinfinite population sizes, high rates of mutagenesis, and rapidity of replication of rna viruses preclude their description by classical population genetics, in which the fitness of a specific phenotype is principally the product of its ability to reproduce successfully 5. This type of genetic organization is termed the quasispecies structure of rna viruses, and it has remarkable biological implications. Ecological connectivity shapes quasispecies structure of. Rna viruses exist as complex mixtures of genotypes, known as quasispecies, where the evolution potential resides in the whole community of related genotypes. The term quasispecies was adopted from a theory of the origin of life in which primitive replicons consisted of mutant distributions, as found experimentally with present day rna viruses. Quasispecies theory is often cited as the theory to describe the evolution of rna viruses, but in recent years several authors have questioned whether quasispecies theory has any relevance for virus evolution 47.
Jenkins gm, worobey m, woelk ch, holmes ec 2001 evidence for the nonquasispecies evolution of rna viruses. Rapid evolution of viral rna genomes the journal of. The coinfection of diverse viruses in a host plant is common. As a consequence, rna viruses replicate as complex and dynamic mutant swarms, called viral quasispecies. It is likely that the quasispecies nature of these rna viruses. Distinctive features of rna virus replication include high mutation rates, high yields, and short replication times. Here, we show that specific rna virus genomes have. Considerably less is known about how its populationbased models apply to the evolutionary behavior of rna viruses in infected hosts, and it will be challenging to translate them to the complex reality of. Viral quasispecies evolution home microbiology and molecular. Rna virus mutations and fitness for survival annual. Probabilistic inference of viral quasispecies subject to.
Viruses can infect all types of life forms, from animals and plants to microorganisms, including bacteria and archaea. In humans, wellknown rna viruses are those that cause sars, influenza or hepatitis c viruses that are not rna viruses use dna for their genome and are called dna viruses viruses have a classification system, invented by david baltimore, a nobel prize winner. A quasispecies is a cloud of diverse variants that are genetically linked through mutation, interact cooperatively on a functional level, and collectively contribute to. Quasispecies theory and the behavior of rna viruses. Is the quasispecies concept relevant to rna viruses. This poses an enormous challenge to vaccine and drug development which, to be effective, must consid.
Viral quasispecies are the mutant distributions also termed mutant swarms or mutant clouds that are generated upon replication of rna viruses, and. These socalled viral quasispecies have been described in vivo through the analysis of molecular and biological clones isolated from viral populations, and more recently using ultradeep sequencing techniques. Evidence for the nonquasispecies evolution of rna viruses. This rna virus circulates as a quasispecies and its genetic heterogeneity has been implicated in the lack of protective immunity against hcv and in its persistence following infection. A virus replicating with a high mutation rate will generate a diverse mutant repertoire over the course of a few generations. To assess quasispecies maintenance during murine infection, we inoculated 6 to 10weekold mice by i.
Details of viral replication and assembly inside an infected host cell are coupled with a population model of a viral infection, allowing the. Bottleneckmediated quasispecies restriction during spread. In hep cspeak, quasispecies refers to small, identifiable viral divergences within a patient. Quasispecies theory in the context of population genetics. Quasispecies theory and the behavior of rna viruses ncbi. Quasispecies structure and persistence of rna viruses. Evolution of rna viruses occurs through disequilibria of collections of closely related mutant spectra or mutant clouds termed viral quasispecies.
In the intervening 40 years, and although exactly how the quasispecies theory can be applied to rna viruses has been the subject of some debate 3,4, the concept has provided an. With regard to rna viruses, the phenotypic quasispecies could correspond to a backbone of nucleotide sites that are essential for virus replication. Impact of rna virus evolution on quasispecies formation. We claim that the quasispecies is at best an unnecessary and at worse a misleading description of rna virus evolution and argue in favor of a population. Viral quasispecies constitute a set of related variants within a virus population e. The theory provided a new definition of wild type, and a conceptual framework for the interpretation of the adaptive potential of rna viruses that. In 1977, manfred eigen and peter schuster proposed the quasispecies model see equation 1 2, which has been applied to understand the evolution of rna viruses, among other genetic phenomena such as the early steps in the origin of life. Mutation rates at defined genomic sites are affected by the nucleotide sequence. Gene surveys suggest that there are spatial and temporal patterns in the composition of rna virus assemblages, but data on their diversity and genetic variability in different oceanographic settings are limited. Rna viruses form complex distributions of closely related but nonidentical genomes that are subjected to a continuous process of genetic variation, competition, and selection fig. This dose of virus is 2 to 5fold above the ld 50 for these mice ref. Here, we report the first pepper viromes that were coinfected by different types of viral genomes. Principles and consequences molecular biology intelligence, unit 14 domingo, esteban on. For the last 30 years, quasispecies theory has provided a populationbased framework for understanding rna viral evolution.
Quasispecies theory has had a profound influence on virology, and experiments with model rna viruses have validated many of its predictions. Pdf quasispecies dynamics of rna viruses researchgate. A large number of medically important viruses, including hiv, hepatitis c virus, and influenza, have rna genomes. Viruses often use alternative receptors and coreceptors, and one or a few amino acid substitutions at exposed surface sites may trigger a shift in receptor specificity. Quasispecies of dengue virus europe pmc article europe pmc.1282 256 1227 1320 1564 401 355 942 1489 18 601 1056 236 302 1090 278 1331 1283 1408 543 1670 6 819 1632 1496 146 401 379 1019 604 1207 216 325 1346 307 189 1632 804 1006 1068 710 1126 73 801 762 1287 529 1457 838