Heterozygous diploid and interspecies SCRaMbLEing.

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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Shen MJ,Wu Y,Yang K,Li Y,Xu H,Zhang H,Li BZ,Li X,Xiao WH,Zhou X,Mitchell LA,Bader JS,Yuan Y,Boeke JD

doi

10.1038/s41467-018-04157-0

subject

Has Abstract

pub_date

2018-05-22 00:00:00

pages

1934

issue

1

issn

2041-1723

pii

10.1038/s41467-018-04157-0

journal_volume

9

pub_type

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