State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, China.
National Center for Protein Sciences Beijing, 38 Life Science Park Road, Beijing 102206, China.
Sci Rep. 2017 Jan 5;7:39949. doi: 10.1038/srep39949.
It is still unclear whether there exist functional constraints on the evolution of protein ubiquitination sites, because most previous studies regarded all protein ubiquitination sites as a whole or only focused on limited structural properties. We tried to clarify the relation between functional constraints and ubiquitination sites evolution. We investigated the evolutionary conservation of human ubiquitination sites in a broad evolutionary scale from G. gorilla to S. pombe, and we found that in organisms originated after the divergence of vertebrate, ubiquitination sites are more conserved than their flanking regions, while the opposite tendency is observed before this divergence time. By grouping the ubiquitination proteins into different functional categories, we confirm that many functional constraints like certain molecular functions, protein tissue expression specificity and protein connectivity in protein-protein interaction network enhance the evolutionary conservation of ubiquitination sites. Furthermore, by analyzing the gains of ubiquitination sites at different divergence time and their functional characters, we validate that the emergences of ubiquitination sites at different evolutionary time were also affected by the uncovered functional constraints. The above results suggest that functional constraints on the adaptive evolution of ubiquitination sites increase the opportunity for ubiquitination to synthetically regulate various cellular and developmental processes during evolution.
目前尚不清楚蛋白质泛素化位点的进化是否存在功能限制，因为之前的大多数研究都将所有蛋白质泛素化位点视为一个整体，或者只关注有限的结构特性。我们试图澄清功能限制与泛素化位点进化之间的关系。我们在从 G. gorilla 到 S. pombe 的广泛进化尺度上研究了人类泛素化位点的进化保守性，我们发现，在脊椎动物分化后的生物中，泛素化位点比其侧翼区域更保守，而在这个分化时间之前，则观察到相反的趋势。通过将泛素化蛋白分为不同的功能类别，我们证实了许多功能限制，如某些分子功能、蛋白质组织表达特异性以及蛋白质-蛋白质相互作用网络中的蛋白质连接性，增强了泛素化位点的进化保守性。此外，通过分析不同进化时间泛素化位点的获得及其功能特征，我们验证了不同进化时间泛素化位点的出现也受到未被揭示的功能限制的影响。上述结果表明，泛素化位点适应性进化的功能限制增加了泛素化在进化过程中综合调节各种细胞和发育过程的机会。
