Gains of ubiquitylation sites in highly conserved proteins in the human lineage

BMC Bioinformatics

Dong Seon Kim¹  Yoonsoo Hahn¹ 

[1] Department of Life Science, Research Center for Biomolecules and Biosystems, Chung-Ang University, Seoul, 156-756, Korea

关键词: Molecular evolution;    Human genome;    Human evolution;    Ubiquitylation;   

Others  :  1088064
DOI  :  10.1186/1471-2105-13-306

 received in 2012-05-26, accepted in 2012-11-14,  发布年份 2012

【 摘 要 】

Background

Post-translational modification of lysine residues of specific proteins by ubiquitin modulates the degradation, localization, and activity of these target proteins. Here, we identified gains of ubiquitylation sites in highly conserved regions of human proteins that occurred during human evolution.

Results

We analyzed human ubiquitylation site data and multiple alignments of orthologous mammalian proteins including those from humans, primates, other placental mammals, opossum, and platypus. In our analysis, we identified 281 ubiquitylation sites in 252 proteins that first appeared along the human lineage during primate evolution: one protein had four novel sites; four proteins had three sites each; 18 proteins had two sites each; and the remaining 229 proteins had one site each. PML, which is involved in neurodevelopment and neurodegeneration, acquired three sites, two of which have been reported to be involved in the degradation of PML. Thirteen human proteins, including ERCC2 (also known as XPD) and NBR1, gained human-specific ubiquitylated lysines after the human-chimpanzee divergence. ERCC2 has a Lys/Gln polymorphism, the derived (major) allele of which confers enhanced DNA repair capacity and reduced cancer risk compared with the ancestral (minor) allele. NBR1 and eight other proteins that are involved in the human autophagy protein interaction network gained a novel ubiquitylation site.

Conclusions

The gain of novel ubiquitylation sites could be involved in the evolution of protein degradation and other regulatory networks. Although gains of ubiquitylation sites do not necessarily equate to adaptive evolution, they are useful candidates for molecular functional analyses to identify novel advantageous genetic modifications and innovative phenotypes acquired during human evolution.

【 授权许可】

   
2012 Kim and Hahn; licensee BioMed Central Ltd.

【 图 表 】

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