Global epistasis on fitness landscapes

Juan Diaz-Colunga, Abigail Skwara, Karna Gowda, Ramon Diaz-Uriarte, Mikhail Tikhonov, Djordje Bajic, Alvaro Sanchez

Research output: Contribution to journalReview articlepeer-review

15 Scopus citations


Epistatic interactions between mutations add substantial complexity to adaptive landscapes and are often thought of as detrimental to our ability to predict evolution. Yet, patterns of global epistasis, in which the fitness effect of a mutation is well-predicted by the fitness of its genetic background, may actually be of help in our efforts to reconstruct fitness landscapes and infer adaptive trajectories. Microscopic interactions between mutations, or inherent nonlinearities in the fitness landscape, may cause global epistasis patterns to emerge. In this brief review, we provide a succinct overview of recent work about global epistasis, with an emphasis on building intuition about why it is often observed. To this end, we reconcile simple geometric reasoning with recent mathematical analyses, using these to explain why different mutations in an empirical landscape may exhibit different global epistasis patterns - ranging from diminishing to increasing returns. Finally, we highlight open questions and research directions. This article is part of the theme issue 'Interdisciplinary approaches to predicting evolutionary biology'.

Original languageEnglish
Article number20220053
JournalPhilosophical Transactions of the Royal Society B: Biological Sciences
Issue number1877
StatePublished - May 22 2023


  • fitness landscapes
  • global epistasis
  • idiosyncratic epistasis


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