N-glycoproteins exhibit a positive expression level-evolutionary rate correlation.

The different proteins of any proteome evolve at enormously different rates. One of the primary factors influencing rates of protein evolution is expression level, with highly expressed proteins tending to evolve at slow rates. This phenomenon, known as the expression level-evolutionary rate (E-R) anticorrelation, has been attributed to the abundance-dependent deleterious effects of misfolding or misinteraction. We have recently shown that secreted proteins either lack an E-R anticorrelation or exhibit a significantly reduced E-R anticorrelation. This effect may be due to the strict quality control to which secreted proteins are subject in the endoplasmic reticulum (which is expected to reduce the rate of misfolding and its deleterious effects) or to their extracellular location (expected to reduce the rate of misinteraction and its deleterious effects). Among secreted proteins, N-glycosylated ones are under particularly strong quality control. Here we investigate how N-linked glycosylation affect the E-R anticorrelation. Strikingly, we observe a positive E-R correlation among N-glycosylated proteins. I.e., N-glycoproteins that are highly expressed evolve at faster rates than lowly expressed N-glycoproteins, in contrast to what is observed among intracellular proteins. This article is protected by copyright. All rights reserved.