Evidence for Positive Epistasis in HIV-1 (original) (raw)

Abstract

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.

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We acknowledge the ViroLogic Clinical Reference Laboratory for their efforts in generating the replication capacity and PR/RT sequence data and C. Althaus, V. Müller, S. Otto, T. Pfeiffer, and M. Salathé for valuable comments. S.B. acknowledges the Swiss National Science Foundation for financial support. The development of the drug resistance database and replication capacity assay used in this study was funded in part by Small Business Innovative Research–Advanced Technology Grants from the National Institute of Allergy and Infectious Diseases, NIH (R43 AI057068 and R43 AI050321). S.B. is an equity holder in ViroLogic, Inc.