page_title: Viral quasispecies
section_title: Bottlenecks
hierarchical_section_title: Viral quasispecies / Bottlenecks
caption_attribution_description: English: Illustration of bottleneck of different severity, defined by the different circles inserted in the entire population (large rectangle) and the outer rectangles. Symbols represent mutant classes. Taken from&#91;1&#93;, with permission from the American Society from Microbiology, Washington DC, USA.
context_page_description: A viral quasispecies is a population structure of viruses with a large numbers of variant genomes. 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 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 the interpretation of the adaptive potential of RNA viruses that contrasted with classical studies based on consensus sequences.
context_section_description: A means to interrupt the participation of individual genomes in interactions with their mutant spectrum is for the quasispecies swarm to undergo drastic reductions in population size that isolate one or few individual genomes from their surroundings. Such reductions are termed bottlenecks, and they have an important participation in shaping evolutionary lineages for all kinds of organisms, and also for viruses. They occur frequently not only upon host-to host transmission but also inside infected hosts, and they can perturb positive and negative selection events in processes that are difficult to identify and characterize.
  Drastic bottleneck events have been reproduced with laboratory populations of viruses in the form of plaque-to-plaque transfers. This design served to verify experimentally the operation of Müller’s ratchet, or fitness decrease by the irreversible incorporation of mutations in asexual organisms in absence of compensatory mechanisms. The serial bottleneck transfers unveiled the presence rare mutations, not seen in standard laboratory or natural viral populations. In absence of forced bottleneck events, such rare mutations would be lost by negative selection because of their fitness cost. The investigation of how FMDV clones debilitated by Müller’s ratchet regained replicative fitness revealed several alternative molecular pathways for fitness recovery. The implications of this observation went largely unnoticed until recent results with hepatitis C virus (HCV) have also suggested the accessibility of multiple pathways for fitness gain. Also, extensive passage of a biological clone of FMDV in BHK-21 cells conferred the capacity to infect several human cell lines in addition to the expected fitness increase for multiplication in BHK-21 cells. Thus, several lines of evidence suggest that fitness gain in a specific environment may paradoxically broaden the phenotypic potential of a virus. It will be interesting to investigate whether focused adaptation of other viruses to a specific environment may also entail a broadening of diversity, with many phenotypic variants attaining similar fitness levels. If generalized, this broadening of phenotypic space would provide a new interpretation of the molecular basis of adaptation, and explain why adaptation to alternative environments may not lead to attenuation.
  Deprivation of an individual virus from possible suppression, complementation or cooperation, may represent a liberation to initiate a new evolutionary process, or a condemnation to extinction. If liberated from suppression, the isolated genome must replicate and be able to reconstruct a mutant cloud to regain adaptive capability. This has led to the suggestion that high mutation rates evolved to allow such mutant spectrum recovery following bottlenecks. Other models attribute high mutation rates to adaptive optimization independent of bottlenecks, or to a mechanistic consequence of rapid replication. Whatever their ultimate origins, high mutation rates serve the purpose of adaptation in multiple circumstances, not only following bottlenecks. A founder virus can introduce a different phenotype for the ensuing evolution. Evolution of viruses in nature and as disease agents can be viewed as succession of mutant spectrum alterations, subjected to expansions and reductions of population size in a continuous interplay of positive and negative selection and random drift. While short-term (for example, intra-host) evolution is observable and measurable, viruses may appear to be relatively static in the long term for decades (as seen with antigenic variants of FMDV ) or longer. Intra-host evolution is generally more rapid than inter-host evolution, as documented with viruses and other biological systems. Apparent invariance may be the result of selection for long-term survival of populations that have previously frenziedly tested evolutionary outcomes in short-term processes.
caption: Illustration of bottleneck of different severity, defined by the different circles inserted in the entire population (large rectangle) and the outer rectangles. Symbols represent mutant classes.
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