The first eukaryotic kinome tree illuminates the dynamic history of present-day kinases

Abstract

Eukaryotic Protein Kinases (ePKs) are essential for eukaryotic cell signalling. Several phylogenetic trees of the ePK repertoire of single eukaryotes have been published, including the human kinome tree. However, a eukaryote-wide kinome tree was missing due to the large number of kinases in eukaryotes. Using a pipeline that overcomes this problem, we present here the first eukaryotic kinome tree. The tree reveals that the Last Eukaryotic Common Ancestor (LECA) possessed at least 92 ePKs, much more than previously thought. The retention of these LECA ePKs in present-day species is highly variable. Fourteen human kinases with unresolved placement in the human kinome tree were found to originate from three known ePK superfamilies. Further analysis of ePK superfamilies shows that they exhibit markedly diverse evolutionary dynamics between the LECA and present-day eukaryotes. The eukaryotic kinome tree thus unveils the evolutionary history of ePKs, but the tree also enables the transfer of functional information between related kinases.