Inference of epistatic effects in a key mitochondrial protein

Erik D. Nelson, Nick V. Grishin

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


We use Potts model inference to predict pair epistatic effects in a key mitochondrial protein - cytochrome c oxidase subunit 2 - for ray-finned fishes. We examine the effect of phylogenetic correlations on our predictions using a simple exact fitness model, and we find that, although epistatic effects are underpredicted, they maintain a roughly linear relationship to their true (model) values. After accounting for this correction, epistatic effects in the protein are still relatively weak, leading to fitness valleys of depth 2Ns≃-5 in compensatory double mutants. Interestingly, positive epistasis is more pronounced than negative epistasis, and the strongest positive effects capture nearly all sites subject to positive selection in fishes, similar to virus proteins evolving under selection pressure in the context of drug therapy.

Original languageEnglish (US)
Article number062404
JournalPhysical Review E
Issue number6
StatePublished - Jun 11 2018

ASJC Scopus subject areas

  • Statistical and Nonlinear Physics
  • Statistics and Probability
  • Condensed Matter Physics


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