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Science. 2019 Aug 30;365(6456):922-926. doi: 10.1126/science.aay0737.

Programmed chromosome fission and fusion enable precise large-scale genome rearrangement and assembly.

Author information

1
Medical Research Council Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, England, UK.
2
Medical Research Council Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, England, UK. chin@mrc-lmb.cam.ac.uk.

Abstract

The design and creation of synthetic genomes provide a powerful approach to understanding and engineering biology. However, it is often limited by the paucity of methods for precise genome manipulation. Here, we demonstrate the programmed fission of the Escherichia coli genome into diverse pairs of synthetic chromosomes and the programmed fusion of synthetic chromosomes to generate genomes with user-defined inversions and translocations. We further combine genome fission, chromosome transplant, and chromosome fusion to assemble genomic regions from different strains into a single genome. Thus, we program the scarless assembly of new genomes with nucleotide precision, a key step in the convergent synthesis of genomes from diverse progenitors. This work provides a set of precise, rapid, large-scale (megabase) genome-engineering operations for creating diverse synthetic genomes.

PMID:
31467221
DOI:
10.1126/science.aay0737

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