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Science 26 November 2004:
Vol. 306. no. 5701, pp. 1547 - 1550
DOI: 10.1126/science.1101786
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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

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