Key Lab of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, People's Republic of China.
University of Chinese Academy of Sciences, Beijing, People's Republic of China.
BMC Genomics. 2018 Jun 4;19(1):431. doi: 10.1186/s12864-018-4661-6.
Rapid evolution of phosphorylation sites could provide raw materials of natural selection to fit the environment by rewiring the regulation of signal pathways. However, a large part of phosphorylation sites was suggested to be non-functional. Although the new-arising phosphorylation sites with little functional implications prevailed in fungi, the evolutionary performance of vertebrate phosphorylation sites remained elusive.
In this study, we evaluated the functionality of human and mouse phosphorylation sites by dividing them into old, median and young age groups based on the phylogeny of vertebrates. We found the sites in the old group were more likely to be functional and involved in signaling pathways than those in the young group. A smaller proportion of sites in the young group originated from aspartate/glutamate, which could restore the ancestral functions. In addition, both the phosphorylation level and breadth was increased with the evolutionary age. Similar to cases in fungi, these results implied that the newly emerged phosphorylation sites in vertebrates were also more likely to be non-functional, especially for serine and threonine phosphorylation in disordered regions.
This study provided not only insights into the dynamics of phosphorylation evolution in vertebrates, but also new clues to identify the functional phosphorylation sites from massive noisy data.
磷酸化位点的快速进化可以通过重新连接信号通路的调控，为自然选择提供原材料，以适应环境。然而，很大一部分磷酸化位点被认为是无功能的。尽管真菌中新出现的具有较小功能意义的磷酸化位点占优势，但脊椎动物磷酸化位点的进化表现仍不清楚。
在这项研究中，我们根据脊椎动物的系统发育，将人类和小鼠的磷酸化位点分为老年、中年和年轻组，评估它们的功能。我们发现，老年组的磷酸化位点比年轻组更有可能具有功能，并参与信号通路。年轻组中源自天冬氨酸/谷氨酸的磷酸化位点比例较小，可能恢复了祖先的功能。此外，磷酸化水平和广度都随进化年龄的增加而增加。与真菌中的情况类似，这些结果表明，脊椎动物中新出现的磷酸化位点也更可能是无功能的，特别是在无序区域的丝氨酸和苏氨酸磷酸化。
本研究不仅深入了解了脊椎动物磷酸化进化的动态，而且为从大量嘈杂数据中识别功能磷酸化位点提供了新的线索。
