Pandya Siddharth, Struck Travis J, Mannakee Brian K, Paniscus Mary, Gutenkunst Ryan N
Department of Molecular and Cellular Biology, University of Arizona.
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.
Mol Biol Evol. 2015 Jan;32(1):144-52. doi: 10.1093/molbev/msu284. Epub 2014 Oct 13.
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.
蛋白质酪氨酸磷酸化是后生动物中的一种关键调控修饰，相应的激酶酶已发生了显著的多样化。这种多样化与全基因组范围内蛋白质酪氨酸含量的降低相关，最近有人提出这种降低是由选择驱动的，以避免可能有害的随意磷酸化。我们检验了这个有趣假设的三个预测。1）对于由于局部溶剂可及性或结构无序而更可能被磷酸化的残基，选择应该更强。2）对于由于丰度高而更可能被随意磷酸化的蛋白质，选择应该更强。我们通过比较人类和酵母直系同源蛋白内部及之间酪氨酸的分布来检验这些预测。3）对产生酪氨酸的突变的选择应该比对去除酪氨酸的突变的选择更强。我们使用人类群体基因组变异数据来检验这个预测。我们发现，与其他氨基酸相比，酪氨酸的所有这三种预测效应都较小，这表明针对有害磷酸化的选择在驱动后生动物酪氨酸丢失方面并不占主导地位。
