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Quasispecies theory and the behavior of RNA viruses.

Lauring AS, Andino R - PLoS Pathog. (2010)

Bottom Line: These viruses replicate with extremely high mutation rates and exhibit significant genetic diversity.For the last 30 years, quasispecies theory has provided a population-based framework for understanding RNA viral evolution.Here, we discuss basic principles of quasispecies theory and describe its relevance for our understanding of viral fitness, virulence, and antiviral therapeutic strategy.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, University of California, San Francisco, San Francisco, California, United States of America.

ABSTRACT
A large number of medically important viruses, including HIV, hepatitis C virus, and influenza, have RNA genomes. These viruses replicate with extremely high mutation rates and exhibit significant genetic diversity. This diversity allows a viral population to rapidly adapt to dynamic environments and evolve resistance to vaccines and antiviral drugs. For the last 30 years, quasispecies theory has provided a population-based framework for understanding RNA viral evolution. A quasispecies is a cloud of diverse variants that are genetically linked through mutation, interact cooperatively on a functional level, and collectively contribute to the characteristics of the population. Many predictions of quasispecies theory run counter to traditional views of microbial behavior and evolution and have profound implications for our understanding of viral disease. Here, we discuss basic principles of quasispecies theory and describe its relevance for our understanding of viral fitness, virulence, and antiviral therapeutic strategy.

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Related in: MedlinePlus

RNA viruses exist as a quasispecies.A virus replicating with a high mutation rate will generate a diverse mutant repertoire over the course of a few generations. In these trees, each branch indicates two variants linked by a point mutation and the concentric circles represent serial replication cycles. The resulting distribution is often represented as a cloud centered on a master sequence. This two dimensional schematic is a vast oversimplification of the intraquasispecies connectivity. In the mathematical formulations of quasispecies theory, sequence space is multidimensional, with numerous branches between variants.
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ppat-1001005-g001: RNA viruses exist as a quasispecies.A virus replicating with a high mutation rate will generate a diverse mutant repertoire over the course of a few generations. In these trees, each branch indicates two variants linked by a point mutation and the concentric circles represent serial replication cycles. The resulting distribution is often represented as a cloud centered on a master sequence. This two dimensional schematic is a vast oversimplification of the intraquasispecies connectivity. In the mathematical formulations of quasispecies theory, sequence space is multidimensional, with numerous branches between variants.

Mentions: The genetic organization of populations is often depicted using the concept of sequence space, a geometric representation of all possible sequences where physical distance reflects genetic similarity. For example, a given viral genome will undergo replication and generate hundreds of progeny that differ at roughly one position (Figure 1). Subsequent rounds of replication will generate a more complex mutant distribution with variants lying farther away from each other in sequence space. This ensemble of mutants forms a “cloud” of variants, or quasispecies, in which mutation generates a swarm of candidate genomes that is pruned by natural selection. According to population genetics, the frequency of a given variant in a population is closely approximated by its ability to survive and reproduce—its fitness. In quasispecies formulations, where mutation rates are elevated, frequency is also subject to the probability that the variant will be generated de novo by mutation of its neighbors in sequence space [12]. In RNA viruses, the contribution of mutation to genotype frequency is significant, and variants are “coupled” in sequence space [18]. That is, a low fitness variant can be maintained at a higher than expected frequency because it is coupled to a well-represented, higher fitness genotype in sequence space. The phenomenon of mutational coupling is one of the defining characteristics of a quasispecies, as it places individual mutants within a functional network of variants [2].


Quasispecies theory and the behavior of RNA viruses.

Lauring AS, Andino R - PLoS Pathog. (2010)

RNA viruses exist as a quasispecies.A virus replicating with a high mutation rate will generate a diverse mutant repertoire over the course of a few generations. In these trees, each branch indicates two variants linked by a point mutation and the concentric circles represent serial replication cycles. The resulting distribution is often represented as a cloud centered on a master sequence. This two dimensional schematic is a vast oversimplification of the intraquasispecies connectivity. In the mathematical formulations of quasispecies theory, sequence space is multidimensional, with numerous branches between variants.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2908548&req=5

ppat-1001005-g001: RNA viruses exist as a quasispecies.A virus replicating with a high mutation rate will generate a diverse mutant repertoire over the course of a few generations. In these trees, each branch indicates two variants linked by a point mutation and the concentric circles represent serial replication cycles. The resulting distribution is often represented as a cloud centered on a master sequence. This two dimensional schematic is a vast oversimplification of the intraquasispecies connectivity. In the mathematical formulations of quasispecies theory, sequence space is multidimensional, with numerous branches between variants.
Mentions: The genetic organization of populations is often depicted using the concept of sequence space, a geometric representation of all possible sequences where physical distance reflects genetic similarity. For example, a given viral genome will undergo replication and generate hundreds of progeny that differ at roughly one position (Figure 1). Subsequent rounds of replication will generate a more complex mutant distribution with variants lying farther away from each other in sequence space. This ensemble of mutants forms a “cloud” of variants, or quasispecies, in which mutation generates a swarm of candidate genomes that is pruned by natural selection. According to population genetics, the frequency of a given variant in a population is closely approximated by its ability to survive and reproduce—its fitness. In quasispecies formulations, where mutation rates are elevated, frequency is also subject to the probability that the variant will be generated de novo by mutation of its neighbors in sequence space [12]. In RNA viruses, the contribution of mutation to genotype frequency is significant, and variants are “coupled” in sequence space [18]. That is, a low fitness variant can be maintained at a higher than expected frequency because it is coupled to a well-represented, higher fitness genotype in sequence space. The phenomenon of mutational coupling is one of the defining characteristics of a quasispecies, as it places individual mutants within a functional network of variants [2].

Bottom Line: These viruses replicate with extremely high mutation rates and exhibit significant genetic diversity.For the last 30 years, quasispecies theory has provided a population-based framework for understanding RNA viral evolution.Here, we discuss basic principles of quasispecies theory and describe its relevance for our understanding of viral fitness, virulence, and antiviral therapeutic strategy.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, University of California, San Francisco, San Francisco, California, United States of America.

ABSTRACT
A large number of medically important viruses, including HIV, hepatitis C virus, and influenza, have RNA genomes. These viruses replicate with extremely high mutation rates and exhibit significant genetic diversity. This diversity allows a viral population to rapidly adapt to dynamic environments and evolve resistance to vaccines and antiviral drugs. For the last 30 years, quasispecies theory has provided a population-based framework for understanding RNA viral evolution. A quasispecies is a cloud of diverse variants that are genetically linked through mutation, interact cooperatively on a functional level, and collectively contribute to the characteristics of the population. Many predictions of quasispecies theory run counter to traditional views of microbial behavior and evolution and have profound implications for our understanding of viral disease. Here, we discuss basic principles of quasispecies theory and describe its relevance for our understanding of viral fitness, virulence, and antiviral therapeutic strategy.

Show MeSH
Related in: MedlinePlus