Experimental Evolution in Viruses

Abstract

Experiments in which evolution takes place in real time can help us establish cause–effect relationships that are difficult to infer from the analysis of natural populations. The simplicity, rapid evolution and biomedical relevance of viruses make them a particularly interesting model system for experimental evolution. Bacterial, animal and plant viruses can be passaged under a variety of conditions, either in simple cell culture systems or in vivo to test population biology hypotheses, study the genetic basis of evolution, or predict evolutionary change in nature. Experimental evolution is a conceptually simple and flexible tool which allows us to address issues ranging from the molecular to the ecosystem level. In addition to studying basic processes such as mutation, adaptation, or random genetic drift, viruses can be experimentally evolved to better understand the emergence of drug resistance, explore new antiviral strategies such as lethal mutagenesis, create better attenuated vaccines, or target cancerous cells.

Key Concepts:

  • Experimental evolution can be done with many different model organisms, but microorganisms and viruses offer a series of advantages including their easy manipulation, storability and biomedical relevance.

  • The setup of an evolutionary experiment is conceptually simple and essentially consists of serially transferring viruses from flask to flask or, in vivo, from host to host. However, a careful experimental design is needed to be able to demonstrate which factors are responsible for the evolutionary changes observed in the laboratory.

  • Molecular biology is a powerful tool in virus experimental evolution because it allows us to manipulate viral genomes and to study the molecular basis of evolution.

  • Viruses can adapt to many different laboratory environments, but these adaptations often come at the cost of decreased performance in alternative environments, demonstrating the existence of certain limits to adaptation, or fitness tradeoffs.

  • Viral experimental evolution has both stochastic and deterministic components. Therefore, although viral evolution is not easy to predict, it shows some regular patterns.

  • The role played by population–genetic factors such as the population size or the mutation rate have been extensively studied in viruses, and several important generalisations have been established.

  • Experimental evolution has inspired new strategies to combat viral disease, including the use of selective mutagens to damage viral genomes or the use of less evolvable strains to create more effective and safer vaccines.

Keywords: virology; evolutionary biology; population genetics; biomedicine; molecular biology

Figure 1.

Typical experimental evolution scheme. Founder clones are obtained by picking well‐isolated plaques from a reference stock and used to initiate serial transfers (passages) under predefined conditions. Infections can be carried out in microtubes as shown here or in flasks, plates, and even in vivo. Carrying out replicate evolutionary lines and including control lines is important to establish the statistical significance of the results. Downstream analyses can be of any type, but the most common ones are fitness assays and sequencing. Sample storage at ultra‐low temperature makes it possible to carry out these analyses simultaneously for initial, intermediate, and final time points, thus facilitating comparison. Here, the typical fitness trajectory of large populations passaged in a new environment is shown. Sequences in the right indicate hypothetical genetic changes fixed during the experiment.

Figure 2.

Evolution in Wright's fitness landscapes. A landscape with several peaks is shown. Selection pushes populations towards peaks (adaptation), whereas processes of fitness decay such as random genetic drift and, in some cases, mutagenesis pushes them towards valleys. One population starting at a given low‐fitness region may evolve towards different peaks in different experimental replicates (divergence), and populations starting at different regions may converge to the same peak. Efficient selection guarantees that populations will reach peaks, but these peaks might be only local optima. In the absence of other evolutionary forces, selection may fail to move a population from one peak to another.

close

References

Agudelo‐Romero P, Carbonell P, Pérez‐Amador MA and Elena SF (2008) Virus adaptation by manipulation of host's gene expression. PLoS ONE 3: e2397.

Anderson JP, Daifuku R and Loeb LA (2004) Viral error catastrophe by mutagenic nucleosides. Annual Review of Microbiology 58: 183–205.

Belshaw R, Gardner A, Rambaut A and Pybus OG (2008) Pacing a small cage: mutation and RNA viruses. Trends in Ecology and Evolution 23: 188–193.

Bruyere A, Wantroba M, Flasinski S et al. (2000) Frequent homologous recombination events between molecules of one RNA component in a multipartite RNA virus. Journal of Virology 74: 4214–4219.

Bull JJ, Badgett MR, Wichman HA et al. (1997) Exceptional convergent evolution in a virus. Genetics 147: 1497–1507.

Bull JJ and Molineux IJ (2008) Predicting evolution from genomics: experimental evolution of bacteriophage T7. Heredity 100: 453–463.

Bull JJ, Sanjuán R and Wilke CO (2007a) Theory of lethal mutagenesis for viruses. Journal of Virology 81: 2930–2939.

Bull JJ, Springman R and Molineux IJ (2007b) Compensatory evolution in response to a novel RNA polymerase: orthologous replacement of a central network gene. Molecular Biology and Evolution 24: 900–908.

Chao L (1990) Fitness of RNA virus decreased by Muller′s ratchet. Nature 348: 454–455.

Chare ER, Gould EA and Holmes EC (2003) Phylogenetic analysis reveals a low rate of homologous recombination in negative‐sense RNA viruses. Journal of General Virology 84: 2691–2703.

Cuevas JM, Elena SF and Moya A (2002) Molecular basis of adaptive convergence in experimental populations of RNA viruses. Genetics 162: 533–542.

Dawkins R (1996) Climbing Mount Improbable. Penguin Books.

Domingo E, Grande‐Pérez A and Martín V (2008) Future prospects for the treatment of rapidly evolving viral pathogens: insights from evolutionary biology. Expert Opinion on Biological Therapy 8: 1455–1460.

Duarte E, Clarke D, Moya A et al. (1992) Rapid fitness losses in mammalian RNA virus clones due to Muller's ratchet. Proceedings of the National Academy of Sciences of the USA 89: 6015–6019.

Duffy S, Turner PE and Burch CL (2006) Pleiotropic costs of niche expansion in the RNA bacteriophage Φ6. Genetics 172: 751–757.

Eigen M, McCaskill J and Schuster P (1988) Molecular quasi‐species. Journal of Physical Chemistry 92: 6881–6891.

Elena SF and Sanjuán R (2005) On the adaptive value of high mutation rates in RNA viruses: separating causes from consequences. Journal of Virology 79: 11555–11558.

Garland T and Rose MR (2009) Experimental Evolution. Berkeley, CA: University of California Press.

Gebauer F, Posthumus WP, Correa I et al. (1991) Residues involved in the antigenic sites of transmissible gastroenteritis coronavirus S glycoprotein. Virology 183: 225–238.

Gerrish PJ and Lenski RE (1998) The fate of competing beneficial mutations in an asexual population. Genetica 102–103: 127–144.

Hartl DL and Clark AG (2007) Principles of Population Genetics. Sunderland, MA: Sinauer Associates.

Holland JJ, Domingo E, de la Torre JC and Steinhauer DA (1990) Mutation frequencies at defined single codon sites in vesicular stomatitis virus and poliovirus can be increased only slightly by chemical mutagenesis. Journal of Virology 64: 3960–3962.

Holland JJ, Spindler K, Horodyski F et al. (1982) Rapid evolution of RNA genomes. Science 215: 1577–1585.

de la Iglesia F and Elena SF (2007) Fitness declines in tobacco etch virus upon serial bottleneck transfers. Journal of Virology 81: 4941–4947.

Jetzt AE, Yu H, Klarmann GJ et al. (2000) High rate of recombination throughout the human immunodeficiency virus type 1 genome. Journal of Virology 74: 1234–1240.

Johnson T and Barton NH (2002) The effect of deleterious alleles on adaptation in asexual populations. Genetics 162: 395–411.

Knies JL, Izem R, Supler KL et al. (2006) The genetic basis of thermal reaction norm evolution in lab and natural phage populations. PLoS Biology 4: e201.

Lichty BD, Power AT, Stojdl DF and Bell JC (2004) Vesicular stomatitis virus: re‐inventing the bullet. Trends in Molecular Medicine 10: 210–216.

Martínez‐Picado J, dePasquale MP, Kartsonis N et al. (2000) Antiretroviral resistance during successful therapy of HIV type 1 infection. Proceedings of the National Academy of Sciences of the USA 97: 10948–10953.

Mills DR, Peterson RL and Spiegelman S (1967) An extracellular Darwinian experiment with a self‐duplicating nucleic acid molecule. Proceedings of the National Academy of Sciences of the USA 58: 217–224.

Miralles R, Gerrish PJ, Moya A and Elena SF (1999) Clonal interference and the evolution of RNA virus. Science 285: 1745–1747.

Novella IS, Ball LA and Wertz GW (2004) Fitness analyses of vesicular stomatitis strains with rearranged genomes reveal replicative disadvantages. Journal of Virology 78: 9837–9841.

Novella IS, Hershey CL, Escarmís C et al. (1999) Lack of evolutionary stasis during alternating replication of an arbovirus in insect and mammalian cells. Journal of Molecular Biology 287: 459–465.

Oldstone MBA (2010) Viruses, Plagues, and History. New York: Oxford University Press.

Orr HA (2000) The rate of adaptation in asexuals. Genetics 155: 961–968.

Paterson S, Vogwill T, Buckling A et al. (2010) Antagonistic coevolution accelerates molecular evolution. Nature 464: 275–278.

Pincus SE, Diamond DC, Emini EA and Wimmer E (1986) Guanidine‐selected mutants of poliovirus: mapping of point mutations to polypeptide 2C. Journal of Virology 57: 638–646.

Rico P, Ivars P, Elena SF and Hernández C (2006) Insights into the selective pressures restricting Pelargonium flower break virus genome variability: evidence for host adaptation. Journal of Virology 80: 8124–8132.

Sanjuán R (2010) Mutational fitness effects in RNA and ssDNA viruses: common patterns revealed by site‐directed mutagenesis studies. Philosophical Transactions of the Royal Society of London B, Biological Sciences 365: 1975–1982.

Sanjuán R, Moya A and Elena SF (2004) The distribution of fitness effects caused by single‐nucleotide substitutions in an RNA virus. Proceedings of the National Academy of Sciences of the USA 101: 8396–8401.

Sanjuán R, Nebot MR, Chirico N et al. (2010) Viral mutation rates. Journal of Virology 84: 9733–9748.

Sierra S, Dávila M, Lowenstein PR and Domingo E (2000) Response of foot‐and‐mouth disease virus to increased mutagenesis: influence of viral load and fitness in loss of infectivity. Journal of Virology 74: 8316–8323.

Simon‐Loriere E, Galetto R, Hamoudi M et al. (2009) Molecular mechanisms of recombination restriction in the envelope gene of the human immunodeficiency virus. PLoS Pathogens 5: e1000418.

Springman R, Keller T, Molineux I and Bull JJ (2009) Evolution at a high imposed mutation rate: adaptation obscures the load in phage T7. Genetics 184: 221–232.

Turner PE and Elena SF (2000) Cost of host radiation in an RNA virus. Genetics 156: 1465–1470.

Vignuzzi M, Stone JK, Arnold JJ et al. (2006) Quasispecies diversity determines pathogenesis through cooperative interactions in a viral population. Nature 439: 344–348.

Vignuzzi M, Wendt E and Andino R (2008) Engineering attenuated virus vaccines by controlling replication fidelity. Nature Medicine 14: 154–161.

Wichman HA, Badgett MR, Scott LA et al. (1999) Different trajectories of parallel evolution during viral adaptation. Science 285: 422–424.

Wichman HA and Brown CJ (2010) Experimental evolution of viruses: Microviridae as a model system. Philosophical Transactions of the Royal Society of London B, Biological Sciences 365: 2495–2501.

Further Reading

Buckling A, Craig MR, Brockhurst MA and Colegrave N (2009) The Beagle in a bottle. Nature 457: 824–829.

Bull JJ and Wichman HA (2001) Applied evolution. Annual Review of Ecology and Systematics 32: 183–217.

Domingo E (2006) Quasispecies: Concepts and Implications for Virology. Berlin: Springer.

Domingo E, Parrish C and Holland JJ (eds) (2008) Origin and Evolution of Viruses. London: Elsevier.

Duffy S, Shackelton LA and Holmes EC (2008) Rates of evolutionary change in viruses: patterns and determinants. Nature Reviews Genetics 9: 267–276.

Elena SF and Lenski RE (2003) Evolution experiments with microorganisms: the dynamics and genetic bases of adaptation. Nature Reviews Genetics 4: 457–469.

Elena SF and Sanjuán R (2007) Virus evolution: insights from an experimental approach. Annual Review of Ecology Evolution and Systematics 38: 27–52.

Holmes EC (2009) The Evolution and Emergence of RNA Viruses. Oxford: Oxford University Press.

Sanjuán R (2008) Quasispeces and experimental evolution of RNA viruses. In: Mahy BWJ and van Regenmorted MHV (eds) Encyclopedia of Virology, pp. 359, 365. Oxford: Elsevier.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Sanjuán, Rafael, and Domingo‐Calap, Pilar(May 2011) Experimental Evolution in Viruses. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0022857]