The relationships among microRNA regulation, intrinsically disordered regions, and other indicators of protein evolutionary rate - PubMed
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The relationships among microRNA regulation, intrinsically disordered regions, and other indicators of protein evolutionary rate
Sean Chun-Chang Chen et al. Mol Biol Evol. 2011 Sep.
Abstract
Many indicators of protein evolutionary rate have been proposed, but some of them are interrelated. The purpose of this study is to disentangle their correlations. We assess the strength of each indicator by controlling for the other indicators under study. We find that the number of microRNA (miRNA) types that regulate a gene is the strongest rate indicator (a negative correlation), followed by disorder content (the percentage of disordered regions in a protein, a positive correlation); the strength of disorder content as a rate indicator is substantially increased after controlling for the number of miRNA types. By dividing proteins into lowly and highly intrinsically disordered proteins (L-IDPs and H-IDPs), we find that proteins interacting with more H-IDPs tend to evolve more slowly, which largely explains the previous observation of a negative correlation between the number of protein-protein interactions and evolutionary rate. Moreover, all of the indicators examined here, except for the number of miRNA types, have different strengths in L-IDPs and in H-IDPs. Finally, the number of phosphorylation sites is weakly correlated with the number of miRNA types, and its strength as a rate indicator is substantially reduced when other indicators are considered. Our study reveals the relative strength of each rate indicator and increases our understanding of protein evolution.
Figures

Spearman's rank correlations between evolutionary rate (dN/dS) and disorder content (DisCont) or the number of miRNA types (NmiR). (A) All: all proteins under study (9,794 proteins). (B) L-IDPs: lowly and moderately intrinsically disordered proteins (DisCont < 43%; 6,630 proteins); H-IDPs: highly intrinsically disordered proteins (DisCont ≥ 43%; 3,164 proteins). DisCont: the number of disordered residues divided by the protein length; NmiR: the number of miRNA types that regulate the gene under study. Significance:*P value ≤ 0.05, **P value ≤ 0.001,***P value ≤ 0.0001.

Spearman's rank correlations (Rs) between disorder content and the number of miRNA types and between disorder content and evolutionary rate (dN/dS). Proteins are divided into “H-IDPs” and “L-IDPs” groups according to whether the disorder content is higher or lower than the given threshold (the x axis). For example, proteins in the “H-IDPs” group and the “L-IDPs” group with the threshold of 50% are the groups with a disorder content higher and lower than 50%, respectively. Each point stands for the Rs value of the corresponding group. Five disorder thresholds are examined here to see how the correlations change under different thresholds. In (B), “H-IDPs|miRNA” and “L-IDPs|miRNA” represent the partial correlations (controlled for the number of miRNA types that regulate the gene) for the H-IDPs and L-IDPs groups, respectively. In both (A) and (B), points above the dotted line represent correlations significantly greater than zero by Spearman's rank test (P < 0.05).

Rate indicators of protein evolution in (A) L-IDPs and in (B) H-IDPs. Gray and black arrows, respectively, represent negative and positive correlations. The thickness of a line between two indicators indicates the strength of their correlation.
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