ArticlePLoS computational biology2021
Engineering gene overlaps to sustain genetic constructs in vivo.
Article in PLoS computational biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 16 citations in OpenAlex.
- Article
- Major genic factors influencing nitrogen response in rice revealed through in-silico characterization and expression dynamics of a set of novel candidate genes.Molecular biology reports · 2025Article
- AI-directed gene fusing prolongs the evolutionary half-life of synthetic gene circuits.Science advances · 2025Article
- Genetic Entanglement Enables Ultrastable Biocontainment in the Mammalian Gut.ACS synthetic biology · 2025Article
- The design and engineering of synthetic genomes.Nature reviews. Genetics · 2025Review
- GENTANGLE: integrated computational design of gene entanglements.Bioinformatics (Oxford, England) · 2024Article
- Prolonging genetic circuit stability through adaptive evolution of overlapping genes.Nucleic acids research · 2023Article
- Stability, robustness, and containment: preparing synthetic biology for real-world deployment.Current opinion in biotechnology · 2023Review
- Biological factors in the synthetic construction of overlapping genes.BMC genomics · 2021Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Evolution is often an obstacle to the engineering of stable biological systems due to the selection of mutations inactivating costly gene circuits. Gene overlaps induce important constraints on sequences and their evolution. We show that these constraints can be harnessed to increase the stability of costly genes by purging loss-of-function mutations. We combine computational and synthetic biology approaches to rationally design an overlapping reading frame expressing an essential gene within an existing gene to protect. Our algorithm succeeded in creating overlapping reading frames in 80% of E. coli genes. Experimentally, scoring mutations in both genes of such overlapping construct, we found that a significant fraction of mutations impacting the gene to protect have a deleterious effect on the essential gene. Such an overlap thus protects a costly gene from removal by natural selection by associating the benefit of this removal with a larger or even lethal cost. In our synthetic constructs, the overlap converts many of the possible mutants into evolutionary dead-ends, reducing the evolutionary potential of the system and thus increasing its stability over time.
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Registered trials
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