Building synthetic chromosomes from natural DNA

Alessandro L. V. Coradini (), Christopher Ne Ville, Zachary A. Krieger, Joshua Roemer, Cara Hull, Shawn Yang, Daniel T. Lusk and Ian M. Ehrenreich ()
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Alessandro L. V. Coradini: University of Southern California
Christopher Ne Ville: University of Southern California
Zachary A. Krieger: University of Southern California
Joshua Roemer: University of Southern California
Cara Hull: University of Southern California
Shawn Yang: University of Southern California
Daniel T. Lusk: University of Southern California
Ian M. Ehrenreich: University of Southern California

Nature Communications, 2023, vol. 14, issue 1, 1-12

Abstract: Abstract De novo chromosome synthesis is costly and time-consuming, limiting its use in research and biotechnology. Building synthetic chromosomes from natural components is an unexplored alternative with many potential applications. In this paper, we report CReATiNG (Cloning, Reprogramming, and Assembling Tiled Natural Genomic DNA), a method for constructing synthetic chromosomes from natural components in yeast. CReATiNG entails cloning segments of natural chromosomes and then programmably assembling them into synthetic chromosomes that can replace the native chromosomes in cells. We use CReATiNG to synthetically recombine chromosomes between strains and species, to modify chromosome structure, and to delete many linked, non-adjacent regions totaling 39% of a chromosome. The multiplex deletion experiment reveals that CReATiNG also enables recovery from flaws in synthetic chromosome design via recombination between a synthetic chromosome and its native counterpart. CReATiNG facilitates the application of chromosome synthesis to diverse biological problems.

Date: 2023
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DOI: 10.1038/s41467-023-44112-2

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