ArticleNucleic acids research2023
Greedy reduction of Bacillus subtilis genome yields emergent phenotypes of high resistance to a DNA damaging agent and low evolvability.
Article in Nucleic acids research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 25 citations in OpenAlex.
- Comparative analysis of gene importance inmSystems · 2026Article
- Adaptive responses of genome-reduced Bacillus subtilis during enzyme secretion in a breathing vessel culture.Microbial cell factories · 2026Article
- Article
- The design and engineering of synthetic genomes.Nature reviews. Genetics · 2025Review
- The mutational landscape of Bacillus subtilis conditional hypermutators shows how proofreading skews DNA polymerase error rates.Nucleic acids research · 2025Article
- The research on the identification, taxonomy, and comparative genomics analysis of nineFrontiers in microbiology · 2025Article
- Alkane degradation mechanism ofFrontiers in microbiology · 2025Article
- CRISPR-Cas9-driven genome editing inFrontiers in microbiology · 2025Article
- Article
- Evolution recovers the fitness of Acinetobacter baylyi strains with large deletions through mutations in deletion-specific targets and global post-transcriptional regulators.PLoS genetics · 2024Article
- Genome engineering on size reduction and complexity simplification: A review.Journal of advanced research · 2024Review
- CRISPR-aided genome engineering for secondary metabolite biosynthesis in Streptomyces.Journal of industrial microbiology & biotechnology · 2024Review
- Review
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Authors and funding
12 authors at 4 institutions in 3 countries.
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No grant is acknowledged in the PubMed record.
Abstract
Genome-scale engineering enables rational removal of dispensable genes in chassis genomes. Deviating from this approach, we applied greedy accumulation of deletions of large dispensable regions in the Bacillus subtilis genome, yielding a library of 298 strains with genomes reduced up to 1.48 Mb in size. High-throughput physiological phenotyping of these strains confirmed that genome reduction is associated with substantial loss of cell fitness and accumulation of synthetic-sick interactions. Transcriptome analysis indicated that <15% of the genes conserved in our genome-reduced strains exhibited a twofold or higher differential expression and revealed a thiol-oxidative stress response. Most transcriptional changes can be explained by loss of known functions and by aberrant transcription at deletion boundaries. Genome-reduced strains exhibited striking new phenotypes relative to wild type, including a very high resistance (increased >300-fold) to the DNA-damaging agent mitomycin C and a very low spontaneous mutagenesis (reduced 100-fold). Adaptive laboratory evolution failed to restore cell fitness, except when coupled with a synthetic increase of the mutation rate, confirming low evolvability. Although mechanisms underlying this emergent phenotype are not understood, we propose that low evolvability can be leveraged in an engineering strategy coupling reductive cycles with evolutive cycles under induced mutagenesis.
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