Loss of conserved ubiquitylation sites in conserved proteins during human evolution

Park,Dongbin; Goh,Chul Jun; Kim,Hyein; Lee,Ji Seok; Hahn,Yoonsoo

doi:10.3892/ijmm.2018.3772

Loss of conserved ubiquitylation sites in conserved proteins during human evolution

Authors:
- Dongbin Park
- Chul Jun Goh
- Hyein Kim
- Ji Seok Lee
- Yoonsoo Hahn
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Affiliations: Department of Life Science, Chung‑Ang University, Seoul 06974, Republic of Korea
Published online on: July 12, 2018 https://doi.org/10.3892/ijmm.2018.3772
Pages: 2203-2212

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Abstract

Ubiquitylation of lysine residues in proteins serves a pivotal role in the efficient removal of misfolded or unused proteins and in the control of various regulatory pathways by monitoring protein activity that may lead to protein degradation. The loss of ubiquitylated lysines may affect the ubiquitin‑mediated regulatory network and result in the emergence of novel phenotypes. The present study analyzed mouse ubiquitylation data and orthologous proteins from 62 mammals to identify 193 conserved ubiquitylation sites from 169 proteins that were lost in the Euarchonta lineage leading to humans. A total of 8 proteins, including betaine homocysteine S‑methyltransferase, clin and CBS domain divalent metal cation transport mediator 3, ribosome‑binding protein 1 and solute carrier family 37 member 4, lost 1 conserved lysine residue, which was ubiquitylated in the mouse ortholog, following the human‑chimpanzee divergence. A total of 17 of the lost ubiquitylated lysines are also known to be modified by acetylation and/or succinylation in mice. In 8 cases, a novel lysine evolved at positions flanking the lost conserved lysine residues, potentially as a method of compensation. We hypothesize that the loss of ubiquitylation sites during evolution may lead to the development of advantageous phenotypes, which are then fixed by selection. The ancestral ubiquitylation sites identified in the present study may be a useful resource for investigating the association between loss of ubiquitylation sites and the emergence of novel phenotypes during evolution towards modern humans.

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