Supplementary material from "Phosphotyrosine signaling and the origin of animal multicellularity"

The evolution of multicellular animals (i.e., metazoans) from a unicellular ancestor is one of the most important yet least understood evolutionary transitions. Historically, given its indispensable functions in intercellular communication and exclusive presence in metazoans, phosphotyrosine (pTyr) signaling was considered a metazoan-specific evolutionary innovation that might have contributed to the origin of metazoan multicellularity. However, recent studies have led to a new understanding of pTyr signaling evolution and its role in the metazoan origin. Sequence analyses have unraveled a much earlier emergence of pTyr signaling in eukaryotic evolution. Even so, several distinct properties of holozoan pTyr signaling may have paved the way for a hypothesized functional transition of pTyr signaling at the multicellular origin, from environmental sensing to intercellular communication, and for it to evolve as a powerful intercellular signaling system for multicellularity. Biochemical analyses of premetazoan pTyr signaling components have further revealed the premetazoan origin of many key features of metazoan pTyr signaling, and the metazoan establishment of others, including the Csk-mediated negative regulation of the activity of Src, a conserved tyrosine kinase in the Holozoa. Finally, potential future directions are discussed, with a stress on the biological functions of premetazoan pTyr signaling via newly developed gene manipulation tools in non-animal holozoans.