Investigating co-evolution of functionally associated phosphosites in human

Phosphorylation is essential for protein function and signal transduction in eukaryotic cells. With the rapid development of mass spectrometry technology, a large number of phosphosites are identified. However, high-throughput methods of functional characterization for phosphosites are still scarce. In this study, we inspected if the co-evolution property can be used as an indicator to explore function of phosphosites through investigating co-evolutionary relationship between functionally associated phosphosites in human. In practice, the evolution attributes of phosphosites were represented with phylogenetic profiles, and then co-evolutionary correlations of functionally associated phosphosites were detected on three levels: (1) phosphosites within one protein; (2) phosphosites in different proteins participating in the same signal transduction pathways, and (3) general phosphosites. Results of the detection show that co-evolution is a general property of functionally associated phosphosites. This finding suggests to some degree that it is feasible to use the co-evolution property in exploring the function of phosphosites and investigating the functional association between them.