Evolutionary rate correlations reveal long-term co-evolutionary interactions in

Co-evolution between genes can occur for a variety of reasons, including co-expression of genes, epistatic interactions between them, physical interactions of gene products and many others. Co-evolutionary partners of a gene are therefore of great interest in identifying potential factors that contribute to any phenotype of interest. State-of-the-art approaches to detect these interactions use correlations of evolutionary rates across a broader phylogeny, and so by necessity identify interactions only among genes that are present across long evolutionary time periods. This makes the methods unwieldy when interest lies in a single focal organism in which the genes of interest may have evolved in the recent evolutionary past. Here, we present a new approach to calculating evolutionary rate correlations which focuses on extracting maximum coverage for a single focal species, while retaining signals of co-evolution across large clades. We show how this approach is able to identify potential interactions even in highly studied species and highly studied genes, with a focus on the