Coevolution due to physical interactions is not a major driving force behind evolutionary rate covariation

Abstract

Co-functional proteins tend to have rates of evolution that covary across the phylogenetic tree. This correlation between evolutionary rates can be measured, through methods such as evolutionary rate covariation (ERC), and then used to construct gene networks and identify proteins with functional interactions. The cause of this correlation has been hypothesized to result from both compensatory coevolution at physical interfaces and shared changes in selective pressures. This study explores whether coevolution due to compensatory mutations has a stronger effect on the ERC signal than the selective pressure on maintaining overall function. We examined the difference in ERC signal between physically interacting protein domains within complexes as compared to domains of the same proteins that do not physically interact. We found no generalizable relationship between physical interaction and high ERC, although a few complexes ranked physical interactions higher than non-physical interactions. Therefore, we conclude that coevolution due to physical interaction is negligible in the signal captured by ERC, and we hypothesize that the stronger signal instead comes from selective pressures on the protein as a whole and maintenance of the general function.