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PreprintCited by 0RNA and protein synthesis mechanismsProtein Structure and DynamicsEvolution and Genetic Dynamics

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Frameshifts in Tandem Repeats: Consequences on Protein Physicochemical Properties and Function

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Osmanli, Zarifa, Aldrian, Gudrun, Leclercq, Jeremy, Falgarone, Theo, Gomez Bergna, Santiago M., Gori, Denis N. Prada, Oleinikov, Andrew V., Shahmuradov, Ilham, Kajava, Andrey V.·2024·FEBS Journal
DOI 10.1101/2024.06.02.597034PMC PMC12871928

Preprint — published as 10.1111/febs.70273 · Paper page

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Abstract

The genetic code uses three-nucleotide units to encode each amino acid in proteins. Insertions or deletions of nucleotides not divisible by three shift the reading frames, resulting in significantly different protein sequences. These events are disruptive but can also create variability important for evolution. Previous studies suggest that genetic code and gene sequences evolve to minimize frameshift effects, maintaining similar physicochemical properties to their reference proteins. Here, we focused on tandem repeat sequences, known as frameshift hotspots. Using cutting-edge bioinformatics tools, we compared reference and frameshifted protein sequences within tandem repeats across 50 prokaryotic and eukaryotic proteomes. Our analysis revealed several intriguing sequence-structure-function correlations. We showed that in contrast to the general tendency, frameshifts within these regions, especially with short repeats, lead to significant changes: increased hydrophobicity and arginine content, new aggregation-prone and transmembrane regions. Overall, frameshifts have stronger effects on tandem repeat regions compared to non-repetitive sequences, and therefore can be a primary cause of altered functions, cellular localization, and the development of various pathologies.

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Metadata

Authors
Osmanli, Z., Aldrian, G., Leclercq, J., Falgarone, T., Gomez Bergna, S. M., Gori, D. N. P., Oleinikov, A. V., Shahmuradov, I., & Kajava, A. V.
Affiliations
  • Centre National de la Recherche Scientifique (FR)
  • Universidad Nacional de La Plata (AR)
  • Florida Atlantic University (US)
  • Ministry of Science and Education Republic of Azerbaijan (AZ)
Corresponding author
Kajava, Andrey V.
ORCID
Venue
FEBS Journal
Publisher
openRxiv
Published
2024-06-03
Volume
293
Issue
3
Pages
842-858
ISSN
1742-464X (ISSN-L)
DOI
10.1101/2024.06.02.597034
PMC
PMC12871928
OpenAlex
W4414480949
Cited by
0
References
1
FWCI
0.00
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • FEBS Journal (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • CONICET Digital (CONICET) (publishedVersion, cc-by)
  • HAL (submittedVersion)
  • HAL (submittedVersion, cc-by)
Funders
  • Azərbaycan Milli Elmlər Akademiyası
  • European Cooperation in Science and Technology (CA21160)
  • Ministère de l'Education Nationale, de l'Enseignement Superieur et de la Recherche
  • Centre National de la Recherche Scientifique
  • Grand Équipement National De Calcul Intensif
  • Horizon 2020 Framework Programme (H2020-MSCA, H2020-MSCA-RISE)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
Keywords
frameshift mutation, tandem repeats, microsatellite markers, protein structural evolution, protein function evolution, hydrophobicity, arginine content, protein variants, protein localization, essential proteins, genetic code
MeSH terms
Amino Acid Sequence, Humans, Proteins, Frameshift Mutation, Evolution, Molecular, Computational Biology, Tandem Repeat Sequences, Proteome, Hydrophobic and Hydrophilic Interactions

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