LARGE-SCALE GENOMIC REARRANGEMENTS BOOST SCRAMBLE IN SACCHAROMYCES CEREVISIAE

Large-scale genomic rearrangements boost SCRaMbLE in Saccharomyces cerevisiae

Large-scale genomic rearrangements boost SCRaMbLE in Saccharomyces cerevisiae

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Abstract Synthetic Chromosome Rearrangement and Modification by LoxP-mediated Evolution (SCRaMbLE) is a promising tool to study genomic rearrangements.However, the potential of SCRaMbLE to study genomic rearrangements is currently hindered, because a strain containing all 16 synthetic chromosomes is not yet available.Here, we construct SparLox83R, a yeast strain containing Melatonin 83 loxPsym sites distributed across all 16 chromosomes.SCRaMbLE of SparLox83R produces versatile genome-wide genomic rearrangements, including inter-chromosomal events.

Moreover, when combined with synthetic chromosomes, SCRaMbLE of hetero-diploids with SparLox83R leads to increased diversity of genomic rearrangements and relatively faster evolution of traits compared to hetero-diploids only with wild-type Small Bookcase chromosomes.Analysis of the SCRaMbLEd strain with increased tolerance to nocodazole demonstrates that genomic rearrangements can perturb the transcriptome and 3D genome structure and consequently impact phenotypes.In summary, a genome with sparsely distributed loxPsym sites can serve as a powerful tool for studying the consequence of genomic rearrangements and accelerating strain engineering in Saccharomyces cerevisiae.

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