Reciprocal sign epistasis is a necessary condition for multi-peaked fitness landscapes

Frank J. Poelwijk, Sorin Tǎnase-Nicola, Daniel J. Kiviet, Sander J. Tans

Research output: Contribution to journalArticlepeer-review

137 Scopus citations


Having multiple peaks within fitness landscapes critically affects the course of evolution, but whether their presence imposes specific requirements at the level of genetic interactions remains unestablished. Here we show that to exhibit multiple fitness peaks, a biological system must contain reciprocal sign epistatic interactions, which are defined as genetic changes that are separately unfavorable but jointly advantageous. Using Morse theory, we argue that it is impossible to formulate a sufficient condition for multiple peaks in terms of local genetic interactions. These findings indicate that systems incapable of reciprocal sign epistasis will always possess a single fitness peak. However, reciprocal sign epistasis should be pervasive in nature as it is a logical consequence of specificity in molecular interactions. The results thus predict that specific molecular interactions may yield multiple fitness peaks, which can be tested experimentally.

Original languageEnglish (US)
Pages (from-to)141-144
Number of pages4
JournalJournal of Theoretical Biology
Issue number1
StatePublished - Mar 7 2011


  • Adaptation
  • Epistasis
  • Evolution
  • Fitness landscape
  • Specific interactions

ASJC Scopus subject areas

  • Statistics and Probability
  • Modeling and Simulation
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)
  • Applied Mathematics


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