Design of a synthetic yeast genome

Author:

Richardson Sarah M.12ORCID,Mitchell Leslie A.23ORCID,Stracquadanio Giovanni124ORCID,Yang Kun12ORCID,Dymond Jessica S.2ORCID,DiCarlo James E.2ORCID,Lee Dongwon1ORCID,Huang Cheng Lai Victor2ORCID,Chandrasegaran Srinivasan5,Cai Yizhi26ORCID,Boeke Jef D.23ORCID,Bader Joel S.12ORCID

Affiliation:

1. Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21205, USA.

2. High Throughput Biology Center, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

3. Institute for Systems Genetics and Department of Biochemistry and Molecular Pharmacology, New York University Langone Medical Center, New York, NY 10016, USA.

4. School of Computer Science and Electronic Engineering, University of Essex, Wivenhoe Park, Colchester CO4 3SQ, UK.

5. Department of Environmental Health Science, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA.

6. University of Edinburgh, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3BF, UK.

Abstract

We describe complete design of a synthetic eukaryotic genome, Sc2.0, a highly modified Saccharomyces cerevisiae genome reduced in size by nearly 8%, with 1.1 megabases of the synthetic genome deleted, inserted, or altered. Sc2.0 chromosome design was implemented with BioStudio, an open-source framework developed for eukaryotic genome design, which coordinates design modifications from nucleotide to genome scales and enforces version control to systematically track edits. To achieve complete Sc2.0 genome synthesis, individual synthetic chromosomes built by Sc2.0 Consortium teams around the world will be consolidated into a single strain by “endoreduplication intercross.” Chemically synthesized genomes like Sc2.0 are fully customizable and allow experimentalists to ask otherwise intractable questions about chromosome structure, function, and evolution with a bottom-up design strategy.

Funder

National Science Foundation

U.S. Department of Energy

Microsoft Research

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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