The molecular mechanisms for repairing DNA damages and point mutations have been well understood but it remains unclear how a frameshift mutation is repaired. Here we report that frameshift reversion occurs in E. coli more frequently than expected and appears to be a targeted gene repair signaled by premature termination codons (PTCs), producing high-level variations in the repaired genes. Genome resequencing shows that the revertant genome is highly stable, and the single-molecule variations in the repaired genes are derived from RNA editing. A multi-omics analysis shows that the expression levels change greatly in most the DNA and RNA manipulating genes. DNA replication, transcription, RNA editing, RNA degradation, nucleotide excision repair, mismatch repair, and homologous recombination were upregulated in the frameshift or revertant, but the base excision repair was not. Moreover, genes and transposons in a duplicate region silenced in wild type E. coli were activated in the frameshift. Finally, we propose a nonsense-mediated gene revising (NMGR) model for frame repair, which also acts as a driving force for molecular evolution. In essence, nonsense mRNAs are recognized, edited, and transported to template the repair of the coding gene by RNA-directed DNA repair, nucleotide excision, mismatch repair, and homologous recombination. Thanks to NMGR, the mutation rate temporarily rises in a frameshift gene, bringing genetic diversity while repairing the frameshift mutation and accelerating the evolution process without a high mutation rate in the genome. ### Competing Interest Statement The authors have declared no competing interest.
- Downloaded 1,737 times
- Download rankings, all-time:
- Site-wide: 14,613
- In genetics: 607
- Year to date:
- Site-wide: 44,105
- Since beginning of last month:
- Site-wide: 45,008
Downloads over time
Distribution of downloads per paper, site-wide
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!