ArticleGenome research2016
SCRaMbLE generates designed combinatorial stochastic diversity in synthetic chromosomes.
Article in Genome research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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Who cites it
79 citing papers in PubMed.
- Advances in large DNA fragment assembly for microbial cell factory engineering.Quantitative biology (Beijing, China) · 2026Review
- High-throughput editing boosts the construction of next-generation microbial cell factories.Synthetic and systems biotechnology · 2026Review
- Synthetic Chromosomes in Yeast: A Platform for Understanding and Programming Eukaryotic Life.Microbial biotechnology · 2026Review
- Programmable promoter editing for precise control of transgene expression.Nature biotechnology · 2026Article
- Large-scale genome structure interrogation via recombinase-mediated rearrangements of multiplexed prime edits in repetitive elements.Nature protocols · 2026Review
- High-throughput yeast engineering in biofoundries: towards autonomous and scalable synthetic biology.FEMS yeast research · 2026Review
- In vivo pathway optimization in yeast via loxpsym-mediated shuffling of upstream activating sequences.Nucleic acids research · 2025Article
- Advances in large-scale DNA engineering with the CRISPR system.Experimental & molecular medicine · 2025Review
- Iterative SCRaMbLE for engineering synthetic genome modules and chromosomes.Nature communications · 2025Article
- Systematic Engineering for Efficient Uric Acid-Degrading Activity in Probiotic YeastACS synthetic biology · 2025Article
- The design and engineering of synthetic genomes.Nature reviews. Genetics · 2025Review
- Multiplex generation and single-cell analysis of structural variants in mammalian genomes.Science (New York, N.Y.) · 2025Article
- Construction and iterative redesign of synXVI a 903 kb synthetic Saccharomyces cerevisiae chromosome.Nature communications · 2025Article
- Hierarchical metabolic engineering for rewiring cellular metabolism.FEMS microbiology reviews · 2025Review
- Towards the first synthetic eukaryotic cell.Biosafety and health · 2024Review
- The de novo design and synthesis of yeast chromosome XIII facilitates investigations on aging.Nature communications · 2024Article
- Programmable promoter editing for precise control of transgene expression.bioRxiv : the preprint server for biology · 2024Article
- Designing a synthetic moss genome using GenoDesigner.Nature plants · 2024Review
- Synthetic Genomics: Repurposing Biological Systems for Applications in Engineering Biology.ACS synthetic biology · 2024Review
- Methodological advances enabled by the construction of a synthetic yeast genome.Cell reports methods · 2024Article
19 more citing papers are in PubMed but not listed here.
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Authors and funding
21 authors.
Funding
Abstract
Synthetic chromosome rearrangement and modification by loxP-mediated evolution (SCRaMbLE) generates combinatorial genomic diversity through rearrangements at designed recombinase sites. We applied SCRaMbLE to yeast synthetic chromosome arm synIXR (43 recombinase sites) and then used a computational pipeline to infer or unscramble the sequence of recombinations that created the observed genomes. Deep sequencing of 64 synIXR SCRaMbLE strains revealed 156 deletions, 89 inversions, 94 duplications, and 55 additional complex rearrangements; several duplications are consistent with a double rolling circle mechanism. Every SCRaMbLE strain was unique, validating the capability of SCRaMbLE to explore a diverse space of genomes. Rearrangements occurred exclusively at designed loxPsym sites, with no significant evidence for ectopic rearrangements or mutations involving synthetic regions, the 99% nonsynthetic nuclear genome, or the mitochondrial genome. Deletion frequencies identified genes required for viability or fast growth. Replacement of 3' UTR by non-UTR sequence had surprisingly little effect on fitness. SCRaMbLE generates genome diversity in designated regions, reveals fitness constraints, and should scale to simultaneous evolution of multiple synthetic chromosomes.
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