Phosphorylation of yeast transcription factors correlates with the evolution of novel sequence and function

Gene duplication is a significant source of novel genes and the dynamics of gene duplicate retention vs loss are poorly understood, particularly in terms of the functional and regulatory specialization of their gene products. We compiled a comprehensive data set of S. cerevisiae phosphosites to study the role of phosphorylation in yeast paralog divergence. We found that proteins coded by duplicated genes created in the Whole Genome Duplication (WGD) event and in a period prior to the WGD are significantly more phosphorylated than other duplicates or singletons. Though the amino acid sequence of each paralog of a given pair tends to diverge fairly similarly from their common ortholog in a related species, the phosphorylated amino acids tend to diverge in sequence from the ortholog at different rates. We observed that transcription factors (TFs) are disproportionately present among the set of duplicate genes and among the set of proteins that are phosphorylated. Interestingly, TFs that occur on higher levels of the transcription network hierarchy (i.e., tend to regulate other TFs) tend to be more phosphorylated than lower-level TFs. We found that TF paralog divergence in expression, binding, and sequence correlates with the abundance of phosphosites. Overall, these studies have important implications for understanding divergence of gene function and regulation in eukaryotes.