ArticlePLoS genetics2013
Correlated occurrence and bypass of frame-shifting insertion-deletions (InDels) to give functional proteins.
Article in PLoS genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed.
- Functional analysis of theMicrobiology spectrum · 2026Article
- Genetic constraints on protein loop evolution: out-of-frame stop codons limitFrontiers in molecular biosciences · 2026Article
- Article
- Structural and energetic analysis of stabilizing indel mutations.bioRxiv : the preprint server for biology · 2024Article
- Insertion-Deletion Events Are Depleted in Protein Regions with Predicted Secondary Structure.Genome biology and evolution · 2024Article
- Remote loop evolution reveals a complex biological function for chitinase enzymes beyond the active site.Nature communications · 2024Article
- Engineering Substrate Promiscuity of Nucleoside Phosphorylase Via an Insertions-Deletions Strategy.JACS Au · 2024Article
- VarSCAT: A computational tool for sequence context annotations of genomic variants.PLoS computational biology · 2023Article
- Development of Omni InDel and supporting database for maize.Frontiers in plant science · 2023Article
- Insertions and deletions mediated functional divergence of Rossmann fold enzymes.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Elucidating the Structural Impacts of Protein InDels.Biomolecules · 2022Article
- Phenotypic mutations contribute to protein diversity and shape protein evolution.Protein science : a publication of the Protein Society · 2022Review
- Mechanisms of protein evolution.Protein science : a publication of the Protein Society · 2022Review
- Pairs of Mutually Compensatory Frameshifting Mutations Contribute to Protein Evolution.Molecular biology and evolution · 2022Article
- Genome- wide structural and functional variant discovery of rice landraces using genotyping by sequencing.Molecular biology reports · 2020Article
- Genome-Wide Discovery of InDel Markers in Sesame (Plants (Basel, Switzerland) · 2020Article
- Article
- Article
- MaveDB: an open-source platform to distribute and interpret data from multiplexed assays of variant effect.Genome biology · 2019Article
- Fitness Effects of Single Amino Acid Insertions and Deletions in TEM-1 β-Lactamase.Journal of molecular biology · 2019Article
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Authors and funding
6 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Short insertions and deletions (InDels) comprise an important part of the natural mutational repertoire. InDels are, however, highly deleterious, primarily because two-thirds result in frame-shifts. Bypass through slippage over homonucleotide repeats by transcriptional and/or translational infidelity is known to occur sporadically. However, the overall frequency of bypass and its relation to sequence composition remain unclear. Intriguingly, the occurrence of InDels and the bypass of frame-shifts are mechanistically related - occurring through slippage over repeats by DNA or RNA polymerases, or by the ribosome, respectively. Here, we show that the frequency of frame-shifting InDels, and the frequency by which they are bypassed to give full-length, functional proteins, are indeed highly correlated. Using a laboratory genetic drift, we have exhaustively mapped all InDels that occurred within a single gene. We thus compared the naive InDel repertoire that results from DNA polymerase slippage to the frame-shifting InDels tolerated following selection to maintain protein function. We found that InDels repeatedly occurred, and were bypassed, within homonucleotide repeats of 3-8 bases. The longer the repeat, the higher was the frequency of InDels formation, and the more frequent was their bypass. Besides an expected 8A repeat, other types of repeats, including short ones, and G and C repeats, were bypassed. Although obtained in vitro, our results indicate a direct link between the genetic occurrence of InDels and their phenotypic rescue, thus suggesting a potential role for frame-shifting InDels as bridging evolutionary intermediates.
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