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, Jef D. Boeke

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number4157
JournalNature communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018

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ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Shen, M. J., Wu, Y., Yang, K., Li, Y., Xu, H., Zhang, H., Li, B. Z., Li, X., Xiao, W. H., Zhou, X., Mitchell, L. A., Bader, J. S., Yuan, Y., & Boeke, J. D. (2018). Heterozygous diploid and interspecies SCRaMbLEing. Nature communications, 9(1), [4157]. https://doi.org/10.1038/s41467-018-04157-0