Frameshifting preserves key physicochemical properties of proteins

Proceedings of the National Academy of Sciences of the United States of America
Lukas BartonekBojan Zagrovic

Abstract

Frameshifts in protein coding sequences are widely perceived as resulting in either nonfunctional or even deleterious protein products. Indeed, frameshifts typically lead to markedly altered protein sequences and premature stop codons. By analyzing complete proteomes from all three domains of life, we demonstrate that, in contrast, several key physicochemical properties of protein sequences exhibit significant robustness against +1 and -1 frameshifts. In particular, we show that hydrophobicity profiles of many protein sequences remain largely invariant upon frameshifting. For example, over 2,900 human proteins exhibit a Pearson's correlation coefficient R between the hydrophobicity profiles of the original and the +1-frameshifted variants greater than 0.7, despite an average sequence identity between the two of only 6.5% in this group. We observe a similar effect for protein sequence profiles of affinity for certain nucleobases as well as protein sequence profiles of intrinsic disorder. Finally, analysis of significance and optimality demonstrates that frameshift stability is embedded in the structure of the universal genetic code and may have contributed to shaping it. Our results suggest that frameshifting may be a powerful e...Continue Reading

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Citations

Dec 16, 2020·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Jacques DemongeotHervé Seligmann
Dec 31, 2020·Life·Alexander Nesterov-MuellerHervé Seligmann
Feb 3, 2021·Open Biology·K A Dill, L Agozzino
Feb 11, 2021·Current Opinion in Structural Biology·Erich Bornberg-BauerAndreas Lange
Feb 11, 2021·Bio Systems·Julie D ThompsonChristian J Michel
May 28, 2021·Molecular Biology and Evolution·Haiqing Xu, Jianzhi Zhang
Aug 11, 2021·Molecular Biology and Evolution·Hana Rozhoňová, Joshua L Payne
Oct 7, 2021·Nature Reviews. Genetics·Bradley W WrightPaul R Jaschke

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