Frameshifting preserves key physicochemical properties of proteins
Lukas Bartonek1, Daniel Braun1, Bojan Zagrovic2
1Department of Structural and Computational Biology, Max Perutz Labs, University of Vienna, Vienna A-1030, Austria.
Summary
Protein frameshifts surprisingly maintain key properties like hydrophobicity, challenging the view that they create nonfunctional proteins. This genetic code feature may drive protein evolution by generating novel sequences with conserved characteristics.
Area of Science:
- * Molecular Biology
- * Bioinformatics
- * Evolutionary Genetics
Background:
- * Protein-coding sequence frameshifts are generally assumed to yield nonfunctional or harmful proteins due to altered sequences and premature stop codons.
- * The impact of frameshifts on the fundamental physicochemical properties of proteins remains largely unexplored across diverse life forms.
Purpose of the Study:
- * To investigate the robustness of protein physicochemical properties against +1 and -1 frameshifts across all domains of life.
- * To explore the evolutionary implications of frameshift stability within the universal genetic code.
Main Methods:
- * Comparative proteome analysis of +1 and -1 frameshifted protein variants.
- * Calculation of Pearson's correlation coefficient (R) for hydrophobicity profiles between original and frameshifted sequences.
- * Analysis of protein sequence profiles for nucleobase affinity and intrinsic disorder.
Main Results:
- * Significant conservation of hydrophobicity profiles was observed between original and frameshifted protein sequences (e.g., R > 0.7 for over 2,900 human proteins despite low sequence identity).
- * Similar robustness was found for profiles related to nucleobase affinity and intrinsic disorder.
- * Frameshift stability is intrinsically linked to the universal genetic code's structure.
Conclusions:
- * Frameshifting is a robust evolutionary mechanism capable of generating proteins with distinct sequences but conserved physicochemical properties.
- * This stability may have played a role in shaping the universal genetic code.
- * The findings challenge the traditional view of frameshifts as solely detrimental, highlighting their potential role in protein evolution and innovation.
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