Heterozygous diploid and interspecies SCRaMbLEing

Michael J. Shen, Yi Wu, Kun Yang, Yunxiang Li, Hui Xu, Haoran Zhang, Bing-Zhi Li, Xia Li, Wen-Hai Xiao, Xiao Zhou, Leslie A. Mitchell, Joel S. Bader, Yingjin Yuan and Jef D. Boeke ()
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Michael J. Shen: NYU Langone Health
Yi Wu: Tianjin University
Kun Yang: Johns Hopkins University
Yunxiang Li: Tianjin University
Hui Xu: Tianjin University
Haoran Zhang: Tianjin University
Bing-Zhi Li: Tianjin University
Xia Li: Tianjin University
Wen-Hai Xiao: Tianjin University
Xiao Zhou: Tianjin University
Leslie A. Mitchell: NYU Langone Health
Joel S. Bader: Johns Hopkins University
Yingjin Yuan: Tianjin University
Jef D. Boeke: NYU Langone Health

Nature Communications, 2018, vol. 9, issue 1, 1-8

Abstract: Abstract SCRaMbLE (Synthetic Chromosome Rearrangement and Modification by LoxP-mediated Evolution) is a genome restructuring technique that can be used in synthetic genomes such as that of Sc2.0, the synthetic yeast genome, which contains hundreds to thousands of strategically positioned loxPsym sites. SCRaMbLE has been used to induce rearrangements in yeast strains harboring one or more synthetic chromosomes, as well as plasmid DNA in vitro and in vivo. Here we describe a collection of heterozygous diploid strains produced by mating haploid semisynthetic Sc2.0 strains to haploid native parental strains. We subsequently demonstrate that such heterozygous diploid strains are more robust to the effects of SCRaMbLE than haploid semisynthetic strains, rapidly improve rationally selected phenotypes in SCRaMbLEd heterozygous diploids, and establish that multiple sets of independent genomic rearrangements are able to lead to similar phenotype enhancements. Finally, we show that heterozygous diploid SCRaMbLE can also be carried out in interspecies hybrid strains.

Date: 2018
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DOI: 10.1038/s41467-018-04157-0

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