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Abstract 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 affects the E–R anticorrelation. Strikingly, we observe apositiveE–R correlation among N‐glycosylated proteins. That is, N‐glycoproteins that are highly expressed evolve at faster rates than lowly expressed N‐glycoproteins, in contrast to what is observed among intracellular proteins.
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Extracellular Domains of Transmembrane Proteins Defy the Expression Level–Evolutionary Rate Anticorrelation
Abstract Highly expressed proteins tend to evolve slowly, a trend known as the expression level–rate of evolution (E–R) anticorrelation. Whereas the reasons for this anticorrelation remain unclear, the most influential hypotheses attribute it to highly expressed proteins being subjected to strong selective pressures to avoid misfolding and/or misinteraction. In accordance with these hypotheses, work in our laboratory has recently shown that extracellular (secreted) proteins lack an E–R anticorrelation (or exhibit a weaker than usual E–R anticorrelation). Extracellular proteins are folded inside the endoplasmic reticulum, where enhanced quality control of folding mechanisms exist, and function in the extracellular space, where misinteraction is unlikely to occur or to produce deleterious effects. Transmembrane proteins contain both intracellular domains (which are folded and function in the cytosol) and extracellular domains (which complete their folding in the endoplasmic reticulum and function in the extracellular space). We thus hypothesized that the extracellular domains of transmembrane proteins should exhibit a weaker E–R anticorrelation than their intracellular domains. Our analyses of human, Saccharomyces and Arabidopsis transmembrane proteins allowed us to confirm our hypothesis. Our results are in agreement with models attributing the E–R anticorrelation to the deleterious effects of misfolding and/or misinteraction.
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- Award ID(s):
- 1818288
- PAR ID:
- 10337390
- Editor(s):
- Golding, Brian
- Date Published:
- Journal Name:
- Genome Biology and Evolution
- Volume:
- 14
- Issue:
- 1
- ISSN:
- 1759-6653
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1093/gbe/evab235
