Fig. 7.

Tyrosine kinases in the evolution of multicellularity and cancer. (A) We propose a series of evolutionary innovations of the tyrosine kinome signaling which potentially contributed to the emergence of metazoan multicellularity. (B) Disease-related mutations tend to occur in more recent tyrosine kinase families. A scatter plot shows how frequently human tyrosine kinases are found to be mutated in genome-wide cancer sequencing studies from the Catalogue Of Somatic Mutations In Cancer (COSMIC) database (Tate et al. 2019). On the y-axis, mutation frequency is measured by the average number of mutations per residue in the tyrosine kinase domain. On the x-axis, each kinase is sorted into a cluster defined by our hierarchy and sorted by their time of emergence. All points were drawn with transparency; as a result, points which appear darker indicate multiple points falling in the same location.