Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 26 November 2004:
Vol. 306. no. 5701, pp. 1547 - 1550
DOI: 10.1126/science.1101786
Prev | Table of Contents | Next

Reports

Evidence for Positive Epistasis in HIV-1

Sebastian Bonhoeffer,1* Colombe Chappey,2 Neil T. Parkin,2 Jeanette M. Whitcomb,2 Christos J. Petropoulos2

Reproductive strategies such as sexual reproduction and recombination that involve the shuffling of parental genomes for the production of offspring are ubiquitous in nature. However, their evolutionary benefit remains unclear. Many theories have identified potential benefits, but progress is hampered by the scarcity of relevant data. One class of theories is based on the assumption that mutations affecting fitness exhibit negative epistasis. Retroviruses recombine frequently and thus provide a unique opportunity to test these theories. Using amino acid sequence data and fitness values from 9466 human immunodeficiency virus 1 (HIV-1) isolates, we find in contrast to these theories strong statistical evidence for a predominance of positive epistasis in HIV-1.

1 Ecology and Evolution, ETH Zurich, ETH Zentrum NW, CH-8092 Zurich, Switzerland.
2 ViroLogic, 345 Oyster Point Boulevard, South San Francisco, CA 94080–1913, USA.



Note added in proof: After this paper had been accepted, a related paper or epistasis in the vesicular stomatitis virus by Sanjuán et al. appeared (29).

* To whom correspondence should be addressed. E-mail: seb{at}env.ethz.ch

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Replication Mode and Landscape Topology Differentially Affect RNA Virus Mutational Load and Robustness.
J. Sardanyes, R. V. Sole, and S. F. Elena (2009)
J. Virol. 83, 12579-12589
   Abstract »    Full Text »    PDF »
Effects of Recombination on Complex Regulatory Circuits.
O. C. Martin and A. Wagner (2009)
Genetics 183, 673-684
   Abstract »    Full Text »    PDF »
The Remarkable Frequency of Human Immunodeficiency Virus Type 1 Genetic Recombination.
A. Onafuwa-Nuga and A. Telesnitsky (2009)
Microbiol. Mol. Biol. Rev. 73, 451-480
   Abstract »    Full Text »    PDF »
The Evolution of Epistasis and Its Links With Genetic Robustness, Complexity and Drift in a Phenotypic Model of Adaptation.
P.-A. Gros, H. Le Nagard, and O. Tenaillon (2009)
Genetics 182, 277-293
   Abstract »    Full Text »    PDF »
Comparative Analysis of Nearly Full-Length Hepatitis C Virus Quasispecies from Patients Experiencing Viral Breakthrough during Antiviral Therapy: Clustered Mutations in Three Functional Genes, E2, NS2, and NS5a.
Z. Xu, X. Fan, Y. Xu, and A. M. Di Bisceglie (2008)
J. Virol. 82, 9417-9424
   Abstract »    Full Text »    PDF »
Coordinated evolution of the hepatitis C virus.
D. S. Campo, Z. Dimitrova, R. J. Mitchell, J. Lara, and Y. Khudyakov (2008)
PNAS 105, 9685-9690
   Abstract »    Full Text »    PDF »
Recombination increases human immunodeficiency virus fitness, but not necessarily diversity.
N. N. V. Vijay, Vasantika, R. Ajmani, A. S. Perelson, and N. M. Dixit (2008)
J. Gen. Virol. 89, 1467-1477
   Abstract »    Full Text »    PDF »
Rapid Adaptive Amplification of Preexisting Variation in an RNA Virus.
R. N. Dutta, I. M. Rouzine, S. D. Smith, C. O. Wilke, and I. S. Novella (2008)
J. Virol. 82, 4354-4362
   Abstract »    Full Text »    PDF »
Distribution of Fitness and Virulence Effects Caused by Single-Nucleotide Substitutions in Tobacco Etch Virus.
P. Carrasco, F. de la Iglesia, and S. F. Elena (2007)
J. Virol. 81, 12979-12984
   Abstract »    Full Text »    PDF »
Evolution Can Favor Antagonistic Epistasis.
M. M. Desai, D. Weissman, and M. W. Feldman (2007)
Genetics 177, 1001-1010
   Abstract »    Full Text »    PDF »
Fitness Declines in Tobacco Etch Virus upon Serial Bottleneck Transfers.
F. de la Iglesia and S. F. Elena (2007)
J. Virol. 81, 4941-4947
   Abstract »    Full Text »    PDF »
Molecular dissection of the potato virus Y VPg virulence factor reveals complex adaptations to the pvr2 resistance allelic series in pepper.
V. Ayme, J. Petit-Pierre, S. Souche, A. Palloix, and B. Moury (2007)
J. Gen. Virol. 88, 1594-1601
   Abstract »    Full Text »    PDF »
Phylogenetic Evidence for Deleterious Mutation Load in RNA Viruses and Its Contribution to Viral Evolution.
O. G. Pybus, A. Rambaut, R. Belshaw, R. P. Freckleton, A. J. Drummond, and E. C. Holmes (2007)
Mol. Biol. Evol. 24, 845-852
   Abstract »    Full Text »    PDF »
HIV-1 Protease Catalytic Efficiency Effects Caused by Random Single Amino Acid Substitutions.
M. Parera, G. Fernandez, B. Clotet, and M. A. Martinez (2007)
Mol. Biol. Evol. 24, 382-387
   Abstract »    Full Text »    PDF »
The HIV positive selection mutation database.
C. Pan, J. Kim, L. Chen, Q. Wang, and C. Lee (2007)
Nucleic Acids Res. 35, D371-D375
   Abstract »    Full Text »    PDF »
In Silico Predicted Robustness of Viroid RNA Secondary Structures. II. Interaction between Mutation Pairs.
R. Sanjuan, J. Forment, and S. F. Elena (2006)
Mol. Biol. Evol. 23, 2123-2130
   Abstract »    Full Text »    PDF »
Epistasis correlates to genomic complexity.
R. Sanjuan and S. F. Elena (2006)
PNAS 103, 14402-14405
   Abstract »    Full Text »    PDF »
A Phylogenetic Method for Detecting Positive Epistasis in Gene Sequences and Its Application to RNA Virus Evolution.
B. Shapiro, A. Rambaut, O. G. Pybus, and E. C. Holmes (2006)
Mol. Biol. Evol. 23, 1724-1730
   Abstract »    Full Text »    PDF »
Effects of random mutations in the human immunodeficiency virus type 1 transcriptional promoter on viral fitness in different host cell environments..
T. van Opijnen, M. C. Boerlijst, and B. Berkhout (2006)
J. Virol. 80, 6678-6685
   Abstract »    Full Text »    PDF »
Quantifying antagonistic epistasis in a multifunctional RNA secondary structure of the Rous sarcoma virus.
R. Sanjuan (2006)
J. Gen. Virol. 87, 1595-1602
   Abstract »    Full Text »    PDF »
Effect of Varying Epistasis on the Evolution of Recombination.
R. D. Kouyos, S. P. Otto, and S. Bonhoeffer (2006)
Genetics 173, 589-597
   Abstract »    Full Text »    PDF »
Comment on "Evidence for Positive Epistasis in HIV-1".
K. Wang, J. E. Mittler, and R. Samudrala (2006)
Science 312, 848b
   Abstract »    Full Text »    PDF »
Response to Comment on "Evidence for Positive Epistasis in HIV-1".
S. Bonhoeffer, C. Chappey, N. T. Parkin, J. M. Whitcomb, and C. J. Petropoulos (2006)
Science 312, 848c
   Abstract »    Full Text »    PDF »
Extensive Recombination among Human Immunodeficiency Virus Type 1 Quasispecies Makes an Important Contribution to Viral Diversity in Individual Patients.
C. Charpentier, T. Nora, O. Tenaillon, F. Clavel, and A. J. Hance (2006)
J. Virol. 80, 2472-2482
   Abstract »    Full Text »    PDF »
Epistasis for Fitness-Related Quantitative Traits in Arabidopsis thaliana Grown in the Field and in the Greenhouse.
R. L. Malmberg, S. Held, A. Waits, and R. Mauricio (2005)
Genetics 171, 2013-2027
   Abstract »    Full Text »    PDF »
Stochastic Interplay between Mutation and Recombination during the Acquisition of Drug Resistance Mutations in Human Immunodeficiency Virus Type 1.
C. L. Althaus and S. Bonhoeffer (2005)
J. Virol. 79, 13572-13578
   Abstract »    Full Text »    PDF »
Adaptive Value of High Mutation Rates of RNA Viruses: Separating Causes from Consequences.
S. F. Elena and R. Sanjuan (2005)
J. Virol. 79, 11555-11558
   Full Text »    PDF »
The effect of host heterogeneity and parasite intragenomic interactions on parasite population structure.
R. Hamilton, M. Boots, and S. Paterson (2005)
Proc R Soc B 272, 1647-1653
   Abstract »    Full Text »    PDF »
Epistasis and the Adaptability of an RNA Virus.
R. Sanjuan, J. M. Cuevas, A. Moya, and S. F. Elena (2005)
Genetics 170, 1001-1008
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)