A phylogenetic method for detecting positive epistasis in gene sequences and its application to RNA virus evolution

Beth Shapiro, Andrew Rambaut, Oliver G. Pybus, Edward C. Holmes

Research output: Contribution to journalArticlepeer-review

Abstract

RNA virus genomes are compact, often containing multiple overlapping reading frames and functional secondary structure. Consequently, it is thought that evolutionary interactions between nucleotide sites are commonplace in the genomes of these infectious agents. However, the role of epistasis in natural populations of RNA viruses remains unclear. To investigate the pervasiveness of epistasis in RNA viruses, we used a parsimony-based computational method to identify pairs of co-occurring mutations along phylogenies of 177 RNA virus genes. This analysis revealed widespread evidence for positive epistatic interactions at both synonymous and nonsynonymous nucleotide sites and in both clonal and recombining viruses, with the majority of these interactions spanning very short sequence regions. These findings have important implications for understanding the key aspects of RNA virus evolution, including the dynamics of adaptation. Additionally, many comparative analyses that utilize the phylogenetic relationships among gene sequences assume that mutations represent independent, uncorrelated events. Our results show that this assumption may often be invalid.

Original languageEnglish
Pages (from-to)1724-1730
Number of pages7
JournalMolecular Biology and Evolution
Volume23
Issue number9
Early online date14 Jun 2006
DOIs
Publication statusPublished - Sep 2006

Keywords

  • coevolution,
  • phylogenetics
  • RNA viruses
  • viral evolution
  • epistasis

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