Directional Selection on Tyrosine Frequences in Eukaryotes Versus Solvent Accessibility

Abstract

Amino acids are the building blocks of proteins, and the composition of those proteins plays a major role in cell signaling. Recently, Tan et al. showed that the overall frequency of the amino acid tyrosine is lower in more complex organisms, which have more cell types and more complex signaling networks. Tan et al. hypothesized that this reduction in tyrosine frequency was driven by selection to avoid potentially deleterious phosphorylation by signaling kinases, termed "spurious cross-talk". Because a phosphate moiety is highly negatively charged, (PO₃³⁻), spurious phosphorylation may disrupt protein folding or inappropriately alter protein activity. Our prediction is that if the loss of tyrosine is driven by selection to avoid spurious phosphorylation, then the loss of tyrosine should be more dramatic on the outside of proteins, because these tyrosines are most accessible to kinases. To test this prediction, we characterize tyrosine frequency versus both organismal complexity (measured by number of tyrosine kinases) and solvent accessibility. To measure absolute solvent accessibility (ASA) of individual residues, we ran the entire proteomes of 16 eukaryotic species through a secondary structure predictor, SPINE-X. In addition, we compared orthologous proteins between humans and yeast to determine whether there was a decrease in tyrosine frequency due to selection, and we analyzed SNP data from 1000 Genomes Phase 1 project to see if there was any ongoing selection in humans at the genomic level. Given that our results suggest that tyrosine is being lost independent of ASA and that there is no change in frequency between Human and Yeast orthologous proteins, we can conclude that the decrease in tyrosine frequency as the complexity of signaling networks increases is not due to the Tan et al. hypothesis of spurious phosphorylation.