Su et al . claim guanine-cytosine (GC) content variation can largely explain the observed tyrosine frequency variation, independent of adaptive evolution of cell-signaling complexity. We found that GC content variation, in the absence of selection for amino acid changes, can only maximally account for 38% of the observed tyrosine frequency variation. We also uncovered other mechanisms acting to reduce tyrosine phosphorylation that further support our previous proposal.