Testing whether Metazoan Tyrosine Loss Was Driven by Selection against Promiscuous Phosphorylation

Siddharth Pandya, Travis J. Struck, Brian K. Mannakee, Mary Paniscus, Ryan N. Gutenkunst

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Protein tyrosine phosphorylation is a key regulatory modification in metazoans, and the corresponding kinase enzymes have diversified dramatically. This diversification is correlated with a genome-wide reduction in protein tyrosine content, and it was recently suggested that this reduction was driven by selection to avoid promiscuous phosphorylation that might be deleterious. We tested three predictions of this intriguing hypothesis. 1) Selection should be stronger on residues that are more likely to be phosphorylated due to local solvent accessibility or structural disorder. 2) Selection should be stronger on proteins that are more likely to be promiscuously phosphorylated because they are abundant. We tested these predictions by comparing distributions of tyrosine within and among human and yeast orthologous proteins. 3) Selection should be stronger against mutations that create tyrosine versus remove tyrosine. We tested this prediction using human population genomic variation data. We found that all three predicted effects are modest for tyrosine when compared with the other amino acids, suggesting that selection against deleterious phosphorylation was not dominant in driving metazoan tyrosine loss.

Original languageEnglish (US)
Pages (from-to)144-152
Number of pages9
JournalMolecular biology and evolution
Issue number1
StatePublished - Jan 1 2015


  • Allele frequency
  • Expression level
  • Phosphorylation
  • Promiscuous
  • Solvent accessibility
  • Structural disorder
  • Tyrosine

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics


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