Testing whether metazoan tyrosine loss was driven by selection against promiscuous phosphorylation.
Testing whether metazoan tyrosine loss was driven by selection against promiscuous phosphorylation.
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DOI：
10.1093/molbev/msu284
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发表时间：
2015
影响因子：
10.7
通讯作者：
Siddharth Pandya;Travis J. Struck;B. Mannakee;Mary Paniscus;R. Gutenkunst
中科院分区：
文献类型：
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作者：
Siddharth Pandya;Travis J. Struck;B. Mannakee;Mary Paniscus;R. Gutenkunst
蛋白质酪氨酸磷酸化是后生动物中一种重要的调节性修饰，相应的激酶也发生了显著的变化。这种多样化与全基因组蛋白酪氨酸含量的减少相关，最近有人提出，这种减少是由选择驱动的，以避免可能有害的混杂磷酸化。我们测试了这个有趣的假设的三个预测。1)由于局部溶剂可及性或结构紊乱，对更可能被磷酸化的残基的选择应该更强。2)选择应该更强的蛋白质，更有可能被混杂磷酸化，因为他们是丰富的。我们通过比较酪氨酸在人类和酵母正构蛋白内部和之间的分布来测试这些预测。3)相对于去除酪氨酸，对产生酪氨酸的突变的选择应该更强。我们使用人类群体基因组变异数据测试了这一预测。我们发现，所有三个预测的影响是适度的酪氨酸相比，其他氨基酸，这表明选择有害的磷酸化并不占主导地位，在驱动后生动物酪氨酸损失。
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.