Correlation of expansion of phospho-tyrosine signaling systems with loss of genome encoded tyrosine residues. A, The genomically-encoded tyrosine content in metazoan organisms and yeast correlate negatively and significantly with organism complexity as measured by distinct cell types (2). Bakers yeast (S. cerevisiae) is included as a unicellular eukaryote for comparison. The species analyzed are yeast (S. cerevisiae), worm, (C. elegans), sea squirt (C. intestinalis), fly (D. melanogaster), mosquito (A. gambiae), zebrafish (D. rerio), tetraodon pufferfish (T. nigroviridis), Japanese pufferfish (T. rubripes), frog (X. tropicalis), chicken (G. gallus), dog (C. familiaris), cow (B. taurus), mouse (M. musculus), rat (R. norvegicus), chimpanzee (P. troglodytes) and human (H. sapiens). B, The number of tyrosine kinase domains in metazoans and yeast correlates negatively and significantly with the number of distinct cell types. C, The fraction of tyrosines in human-yeast ortholog protein pairs. Every point in the scatter plot represents a human-yeast ortholog protein pair where the (x, y) values denote the tyrosine content in human and yeast proteins, respectively. For simplicity, only proteins with an inferred one-to-one orthologous relationship between human and yeast are analyzed (for example, to avoid accelerated sequence divergence due to functional redundancy of paralogs). Orthologous protein pairs lying above the red diagonal (x = y) lines have higher tyrosine composition in yeast than human. The left scatter plot is for 437 human proteins conserved in yeast and known to be tyrosine-phosphorylated and the right plot is for 647 human proteins conserved in yeast not known to be tyrosine-phosphorylated.