Virus Evolution


Viruses are transmissible deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) genetic elements that require a cell for multiplication. Viruses are extremely diverse and ubiquitous in nature. They evolve in continuous interaction with their host cells and organisms, following the general Darwinian principles: genetic variation, competition among variant forms and selection of the most fit variants in a given environment. Viruses probably had an ancient origin and have survived as agents of gene transfer and promoters of cell variation. Evolution of RNA viruses and some DNA viruses can be extremely rapid, fuelled by limited template‐copying fidelity of the replicating polymerases. They form extremely complex mutant clouds termed viral quasispecies, which can acquire features not explainable from the individuals that compose the ensemble. Quasispecies dynamics not only represent a problem for disease prevention and control, but it has inspired new strategies to combat viral disease. One of them is lethal mutagenesis or viral extinction driven by an excess of mutations, often produced by mutagenic nucleotide analogues. New antiviral designs based on lethal mutagenesis are currently under investigation.

Key Concepts:

  • Virions are the virus particles produced on completion of the intracellular replication cycle.

  • Interhost transmission of virions can give rise to disease outbreaks, epidemics or pandemics.

  • Metagenomic studies using deep sequencing methods have unveiled great diversity of viruses in many natural habitats.

  • The ensemble of viruses in our biosphere is termed the ‘virosphere’.

  • Evidence from comparative genomics suggests a long coevolution of cells and viruses on Earth.

  • Recombination and horizontal gene transfers between viral and cellular genes have been abundant during evolution of life.

  • Some proteins that play physiological functions in cells can be recruited as part of the innate immunity against viruses.

  • Population bottlenecks may alter viral fitness and influence evolutionary outcomes.

  • The adaptive potential of viral quasispecies has encouraged research in new strategies for viral disease prevention and control.

Keywords: genome replication; genetic variation; coevolution; quasispecies; mutation; recombination

Figure 1.

Some general concepts of virus evolution. (a) Genomic sequence alignments of related viruses often show conservation of functional domains (blocks) although they may vary in size, nucleotide sequence, relative position or orientation (block depicted by an arrow in the last two genomes). Sequence alignments of related viral genomes are the first data sets to be used for phylogenetic analyses. (b) Viral genomic sequences can be related by phylogenetic trees. Branches represent minimal genetic distances (nucleotide differences) among the different isolates. Clusters of related viruses are often referred to as clades, types or subtypes. Each tip of a branch is represented by a cloud to indicate the multiple variants that are often found in each viral isolate. Clouds are generally larger for RNA viruses than for complex DNA viruses. Deviant representatives of a distant cloud (arrow) may originate a new virus group that will undergo further diversification.

Figure 2.

Mutation rates and frequencies. Cellular DNA replication is several orders of magnitude more accurate than RNA virus genome replication or retrotranscription. An average mutation rate of 10−4 means that one misincorporation error at a given nucleotide template will occur once every 10 000 times that the polymerase copies this specific nucleotide. For both cellular DNA and viral RNA, mutation rates and frequencies much higher than average have been described (hypermutability). For RNA genomes mutation rates and frequencies lower than average may also occur (hypomutability). For specific studies on mutation rates and frequencies, see the References and Further Reading. Terms are defined in Table .

Figure 3.

Viral quasispecies and the effect of sampling events. (a) Horizontal lines represent genomes and symbols on lines represent different types of mutations. A selection event (or a transmission bottleneck, i.e. a single genome is the origin of next distribution) leads to a change in the average sequence (small arrow, right). The average sequence is also termed the consensus sequence, and it is the one that includes at any position the nucleotide found most frequently in that position of the sequence distribution. Sequence distribution is also termed the mutant spectrum or mutant cloud of the quasispecies. Massive infections (large shaded arrow) may result in an invariant consensus sequence despite a dynamic (changing) mutant spectrum. (b) The effect of population size on the heterogeneity of an infecting viral population. In the population delimited by the large external rectangle four types of relevant variants exist (e.g. drug‐resistant mutants depicted as a circle, triangle, square and star). Depending on the sampled size (circles of different diameters) different variants will participate in the next round of infection. Reproduced from Domingo et al. (). © ASM.

Figure 4.

Genetic shift and drift. Two forms of a virus consisting of a genome with eight segments, depicted in black or white, can form a reassortant made of different numbers of black and white segments when the two virus forms coinfect the same cell. The event that leads to the reassortment is genetic shift. When the reassorted (white) segments encode different antigenically relevant proteins the phenomenon is termed antigenic shift. Further evolution through point mutations (depicted as different symbols on the white segments) is termed genetic or antigenic drift.



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Further Reading

Domingo E, Parrish C and Holland JJ (eds) (2008) Origin and Evolution of Viruses, 2nd edn. Oxford: Elsevier.

Eigen M (1992) Steps Towards Life. Oxford: Oxford University Press.

Eigen M (2013) From Strange Simplicity to Complex Familiarity. Oxford: Oxford University Press.

Ehrenfeld E, Domingo E and Ross RP (2010) The Picornaviruses. Washington DC: ASM Press.

Flint SJ, Enquist LW, Racaniello VR and Skalka AM (2009) Principles of Virology. Molecular Biology, Pathogenesis and Control of Animal Viruses, 3rd edn. Washington DC: ASM Press.

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Domingo, Esteban, and Perales, Celia(Apr 2014) Virus Evolution. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0000436.pub3]