The evolutionary dynamics of RNA viruses are complex and their high mutation rates, rapid replication kinetics, and large population sizes present a challenge to traditional population genetics. Quasispecies theory is a mathematical framework that was initially formulated to explain the evolution of life in the “precellular RNA world”. It builds on classical population genetics, but seeks to explore the consequences of error-prone replication and near-infinite population sizes for genome evolution. More recently, quasispecies theory has been used to describe the evolutionary dynamics of RNA viruses, and many of its predictions have been validated experimentally in model systems. Some of these observations challenge more traditional views of evolution and have profound implications for the control and treatment of viral diseases.
This article explains basic aspects of quasispecies theory, describe key experiments that define “quasispecies effects” and highlights how these results may shape our view of viral pathogenesis, antiviral drug development, and vaccine design. It stresses three clinically relevant principles. First, the fitness of a particular virus sequence may be determined more by its freedom to mutate into related sequences than by its own replicative capacity. Second, many viruses operate near a threshold of “error catastrophe” and may be combated by increasing their replication error rates. Third, increasing the fidelity of genome replication may paradoxically attenuate viruses.
Quasispecies Theory and the Behavior of RNA Viruses. PLoS Pathog 6(7): e1001005. doi:10.1371/journal.ppat.1001005
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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