title: Testing whether metazoan tyrosine loss was driven by selection against promiscuous phosphorylation.
abstract: 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.
authors.affiliation: Department of Molecular and Cellular Biology, University of Arizona.
authors.forename: Siddharth
authors.initials: S
authors.lastname: Pandya
authors.affiliation: Department of Molecular and Cellular Biology, University of Arizona.
authors.forename: Travis J
authors.initials: TJ
authors.lastname: Struck
authors.affiliation: Department of Molecular and Cellular Biology, University of Arizona Division of Epidemiology and Biostatistics, Mel and Enid Zuckerman College of Public Health, University of Arizona.
authors.forename: Brian K
authors.initials: BK
authors.lastname: Mannakee
authors.affiliation: Department of Molecular and Cellular Biology, University of Arizona Graduate Interdisciplinary Program in Genetics, University of Arizona.
authors.forename: Mary
authors.initials: M
authors.lastname: Paniscus
authors.affiliation: Department of Molecular and Cellular Biology, University of Arizona rgutenk@email.arizona.edu.
authors.forename: Ryan N
authors.initials: RN
authors.lastname: Gutenkunst
mesh_terms: D000818:Animals; D019143:Evolution, Molecular; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D005787:Gene Frequency; D016681:Genome, Fungal; D015894:Genome, Human; D006801:Humans; D009154:Mutation; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D011506:Proteins / Q000737:chemistry* / Q000235:genetics*; D012641:Selection, Genetic; D014443:Tyrosine / Q000235:genetics* / Q000378:metabolism*; D015003:Yeasts / Q000235:genetics / Q000378:metabolism*
chemical_list: D005656:Fungal Proteins; D011506:Proteins; D014443:Tyrosine; D011494:Protein Kinases
keywords: allele frequency; expression level; phosphorylation; promiscuous; solvent accessibility; structural disorder; tyrosine