Shared information between residues is sufficient to detect pair-wise epistasis in a protein

Abstract

In a comment on our manuscript "Strong selection significantly increases epistatic interactions in the long-term evolution of a protein", Dr. Crona challenges our assertion that shared entropy (that is, information) between two residues implies epistasis between those residues, by constructing an explicit example of three loci (say A, B, and C), where A and B are epistatically linked (leading to shared entropy between A and B), and A and C also depend epistatically (leading to shared entropy between A and C), so that loci B and C are correlated (share entropy).