Before revision:  Here we analyze the evolution of epistasis in the protease of the human immunodeficiency virus type 1 (HIV-1) using genomic sequences collected for almost a decade from  treated and untreated patients, to understand how proteins adapt to a changing environment of treatment over time. We show that mutual information between pairs of residues is a necessary (but not sufficient) condition for epistasis , allowing us to use information as a proxy for epistasis .
After revision:  Here we analyze the evolution of epistasis in the protease of the human immunodeficiency virus type 1 (HIV-1) using genomic sequences collected for almost a decade from treated and untreated patients, to understand how epistasis changes and how those changes impact the long-term evolvability of a protein. We use an information-theoretic proxy for epistasis that quantifies the co-variation between sites, and show that positive information is a necessary (but not sufficient) condition for epistasis , allowing us to use information as a proxy for epistasis .