A viral quasispecies is a population structure of viruses with a large number of variant genomes (related by mutations). Quasispecies result from high mutation rates as mutants arise continually and change in relative frequency as viral replication and selection proceeds.

The theory predicts that a viral quasispecies at a low but evolutionarily neutral and highly connected (that is, flat) region in the fitness landscape will outcompete a quasispecies located at a higher but narrower fitness peak in which the surrounding mutants are unfit. This phenomenon has been called 'the quasispecies effect' or, more recently, the 'survival of the flattest'.

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 within their host. The theory provided a new definition of wild type when describing viruses, and a conceptual framework for a deeper understanding of the adaptive potential of RNA viruses than is offered by classical studies based on simplified consensus sequences.

The quasispecies model is most applicable when the genome size is limited and the mutation rate is high, and so is most relevant to RNA viruses (including important pathogens) because they have high mutation rates (approx one error per round of replication), though the concepts can apply to other biological entities such as reverse transcribing DNA viruses like hepatitis B. In such scenarios, complex distributions of closely related variant genomes are subjected to genetic variation, competition and selection, and may act as a unit of selection. Therefore, the evolutionary trajectory of the viral infection cannot be predicted solely from the characteristics of the fittest sequence. High mutation rates also place an upper limit compatible with inheritable information. Crossing such a limit leads to RNA virus extinction, a transition that is the basis of an antiviral design termed lethal mutagenesis, and of relevance to antiviral medicine.

The relevance of quasispecies in virology has been the subject of extended debate. However, standard clonal analyses and deep sequencing methodologies have confirmed the presence of myriads of mutant genomes in viral populations, and their participation in adaptive processes.

Quasispecies theory was developed in the 1970s by Manfred Eigen and Peter Schuster to explain self-organization and adaptability of primitive replicons (a term used to refer to any replicating entity), as an ingredient of hypercyclic organizations that link genotypic and phenotypic information, as an essential step in the origin of life. The theory portrayed early replicon populations as organized mutant spectra dominated by a master sequence, the one endowed with the highest fitness (replicative capacity) in the distribution. It introduced the notion of a mutant ensemble as a unit of selection, thus emphasizing the relevance of intra-population interactions to understand the response to selective constraints. One of its corollaries is the error threshold relationship, which marks the maximum mutation rate at which the master (or dominant) sequence can stabilize the mutant ensemble. Violation of the error threshold results in loss of dominance of the master sequence and drift of the population in sequence space.

The core quasispecies concepts are described by two fundamental equations: replication with production of error copies, and the error threshold relationship. They capture two major features of RNA viruses at the population level: the presence of a mutant spectrum, and the adverse effect of an increase of mutation rate on virus survival, each with several derivations.

The existence of a mutant spectrum was experimentally evidenced first by clonal analyses of RNA bacteriophage Qβ populations whose replication had been initiated by a single virus particle. Individual genomes differed from the consensus sequence in an average of one to two mutations per individual genome. Fitness of biological clones was inferior to that of the parental, uncloned population, a difference also documented for vesicular stomatitis virus (VSV). The replicative capacity of a population ensemble need not coincide with that of its individual components. The finding that a viral population was essentially a pool of mutants came at a time when mutations in general genetics were considered rare events, and virologists associated a viral genome with a defined nucleotide sequence, as still implied today in the contents of data banks. The cloud nature of Qβ was understood as a consequence of its high mutation rate, calculated in 10⁻⁴ mutations introduced per nucleotide copied, together with tolerance of individual genomes to accept an undetermined proportion of the newly arising mutations, despite fitness costs. The error rate estimated for bacteriophage Qβ has been confirmed, and is comparable to values calculated for other RNA viruses.