dorsal/arxiv
View SchemaWhy highly expressed proteins evolve slowly
| Authors | D. Allan Drummond, Jesse D. Bloom, Christoph Adami, Claus O. Wilke, Frances H. Arnold |
|---|---|
| Categories | |
| ArXiv ID | q-bio/0506002 |
| URL | https://arxiv.org/abs/q-bio/0506002 |
| DOI | 10.1073/pnas.0504070102 |
| Journal | Proc. Nat'l. Acad. Sci. USA 102(40):14338-14343 (2005) |
Abstract
Much recent work has explored molecular and population-genetic constraints on the rate of protein sequence evolution. The best predictor of evolutionary rate is expression level, for reasons which have remained unexplained. Here, we hypothesize that selection to reduce the burden of protein misfolding will favor protein sequences with increased robustness to translational missense errors. Pressure for translational robustness increases with expression level and constrains sequence evolution. Using several sequenced yeast genomes, global expression and protein abundance data, and sets of paralogs traceable to an ancient whole-genome duplication in yeast, we rule out several confounding effects and show that expression level explains roughly half the variation in Saccharomyces cerevisiae protein evolutionary rates. We examine causes for expression's dominant role and find that genome-wide tests favor the translational robustness explanation over existing hypotheses that invoke constraints on function or translational efficiency. Our results suggest that proteins evolve at rates largely unrelated to their functions, and can explain why highly expressed proteins evolve slowly across the tree of life.
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"abstract": "Much recent work has explored molecular and population-genetic constraints on\nthe rate of protein sequence evolution. The best predictor of evolutionary rate\nis expression level, for reasons which have remained unexplained. Here, we\nhypothesize that selection to reduce the burden of protein misfolding will\nfavor protein sequences with increased robustness to translational missense\nerrors. Pressure for translational robustness increases with expression level\nand constrains sequence evolution. Using several sequenced yeast genomes,\nglobal expression and protein abundance data, and sets of paralogs traceable to\nan ancient whole-genome duplication in yeast, we rule out several confounding\neffects and show that expression level explains roughly half the variation in\nSaccharomyces cerevisiae protein evolutionary rates. We examine causes for\nexpression\u0027s dominant role and find that genome-wide tests favor the\ntranslational robustness explanation over existing hypotheses that invoke\nconstraints on function or translational efficiency. Our results suggest that\nproteins evolve at rates largely unrelated to their functions, and can explain\nwhy highly expressed proteins evolve slowly across the tree of life.",
"arxiv_id": "q-bio/0506002",
"authors": [
"D. Allan Drummond",
"Jesse D. Bloom",
"Christoph Adami",
"Claus O. Wilke",
"Frances H. Arnold"
],
"categories": [
"q-bio.PE",
"q-bio.GN"
],
"doi": "10.1073/pnas.0504070102",
"journal_ref": "Proc. Nat\u0027l. Acad. Sci. USA 102(40):14338-14343 (2005)",
"title": "Why highly expressed proteins evolve slowly",
"url": "https://arxiv.org/abs/q-bio/0506002"
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