Evaluation of functionality for serine and threonine phosphorylation with different evolutionary ages in human and...

Rapid evolution of phosphorylation sites could provide raw materials of natural selection to fit the environment by rewiring the regulation of signal pathways. However, a large part of phosphorylation sites was suggested to be non-functional. Although the new-arising phosphorylation sites with little functional implications prevailed in fungi, the evolutionary performance of vertebrate phosphorylation sites remained elusive.

In this study, we evaluated the functionality of human and mouse phosphorylation sites by dividing them into old, median and young age groups based on the phylogeny of vertebrates. We found the sites in the old group were more likely to be functional and involved in signaling pathways than those in the young group. A smaller proportion of sites in the young group originated from aspartate/glutamate, which could restore the ancestral functions. In addition, both the phosphorylation level and breadth was increased with the evolutionary age. Similar to cases in fungi, these results implied that the newly emerged phosphorylation sites in vertebrates were also more likely to be non-functional, especially for serine and threonine phosphorylation in disordered regions.

This study provided not only insights into the dynamics of phosphorylation evolution in vertebrates, but also new clues to identify the functional phosphorylation sites from massive noisy data.