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Journal of Virology, July 2006, p. 6678-6685, Vol. 80, No. 13
0022-538X/06/$08.00+0     doi:10.1128/JVI.02547-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Effects of Random Mutations in the Human Immunodeficiency Virus Type 1 Transcriptional Promoter on Viral Fitness in Different Host Cell Environments{dagger}

Tim van Opijnen,1,2 Maarten C. Boerlijst,2 and Ben Berkhout1*

Department of Human Retrovirology, Academic Medical Centre, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands,1 Section Population Biology, Institute for Biodiversity and Ecosystem Dynamics, University of Amsterdam, Kruislaan 320, 1098 SM Amsterdam, The Netherlands2

Received 6 December 2005/ Accepted 23 March 2006

A mutation's effect on fitness or phenotype may in part depend on the interaction of the mutation with the environment. The resulting phenotype or fitness is important, since it determines the adaptive potential of a species. To date, most studies have focused on alterations to protein-coding regions of the genome and their consequential fitness effects. Non-protein-coding regulatory regions have been largely neglected, although they make up a large and important part of an organism's genome. Here, we use human immunodeficiency virus type 1 as a model system to investigate fitness effects of random mutations in noncoding DNA-binding sites of the transcriptional promoter. We determined 242 fitness values for 35 viral promoter mutants with one, two, or three mutations across seven distinct cellular environments and identified that (i) all mutants have an effect in at least one cellular environment; (ii) fitness effects are highly dependent on the cellular environment; (iii) disadvantageous and advantageous mutations occur at high and similar frequencies; and (iv) epistatic effects of multiple mutations are rare. Our results underline the evolutionary potential of regulatory regions and indicate that DNA-binding sites evolve under strong selection, while at the same time, they are very plastic to environmental change.

* Corresponding author. Mailing address: Department of Human Retrovirology, Academic Medical Centre, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands. Phone: 31 20 566 4822. Fax: 31 20 691 6531. E-mail: b.berkhout{at}amc.uva.nl.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

Journal of Virology, July 2006, p. 6678-6685, Vol. 80, No. 13
0022-538X/06/$08.00+0     doi:10.1128/JVI.02547-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Sardanyes, J., Sole, R. V., Elena, S. F. (2009). Replication Mode and Landscape Topology Differentially Affect RNA Virus Mutational Load and Robustness. J. Virol. 83: 12579-12589 [Abstract] [Full Text]  
  • Dykes, C., Demeter, L. M. (2007). Clinical Significance of Human Immunodeficiency Virus Type 1 Replication Fitness. Clin. Microbiol. Rev. 20: 550-578 [Abstract] [Full Text]  


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