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Movement in proteins requires energy. To this end, natural selection has selected phosphate as the principal energy currency in cells. On the other hand, depicting the state of transcription could come in the form of epigenetic markers, which are modifications on nucleotide residues. But, what are the deeper evolutionary forces that underpin the selection of phosphorylation as a key process for translating molecular information of cellular state into specific phenotype in movement and metabolism at the cellular level? From another perspective, what are the factors that guide the selection of particular phosphosites as principal phosphorylation sites? Seeking answers to the latter question, Villen and coworkers (“Evolution of protein phosphorylation across 18 fungal species”, Science, Link ) used mass spectrometry to profile the phosphoproteome of 18 fungal species and employed discovery science approaches to elucidate specific phosphosite highly conserved for particular functions such as transcription and translation. Using histone protein (H2) and transcription initiator factor (eIF4E) as model proteins for gaining a deeper understanding of the evolutionary forces that shape the annotation of specific phosphosite (from a large library of possible phosphosites) as key molecular effectors of cellular processes such as conformational changes in enzymes and ion channels. Results obtained suggests possible selection forces that define particular phosphosite for function, which are corroborated through assessing kinase motif usage and biochemical assays for the binding affinity between peptide libraries and cell lysates. Looking at a broader landscape of protein phosphorylation, the paper, however, does not yield sufficient insights to answer questions such as how protein phosphorylation first emerged as a defining mechanism for translating stored cellular energy in phosphate groups into movement necessary for protein function and, by extension, that of the cell. Understanding the evolutionary processes that first potentiated protein phosphorylation as well as the specific natural selection factors that resulted in the definition of specific phosphosite for particular function are fundamental questions important to understanding how biology utilizes chemical and physical principles for powering life.
The author read the cited paper and thought deeply about the evolutionary forces that first give rise to phosphorylation as a method for storing cellular energy at the protein level for enabling movement in multi-domain proteins, as well as serving as a marker (i.e., information storage) for identifying specific proteins important for downstream cellular processes. He wrote the preprint.