Total synthesis of a functional designer eukaryotic chromosome

Narayana Annaluru, Héloïse Muller, Leslie A. Mitchell, Sivaprakash Ramalingam, Giovanni Stracquadanio, Sarah M. Richardson, Jessica S. Dymond, Zheng Kuang, Lisa Z. Scheifele, Eric M. Cooper, Yizhi Cai, Karen Zeller, Neta Agmon, Jeffrey S. Han, Michalis Hadjithomas, Jennifer Tullman, Katrina Caravelli, Kimberly Cirelli, Zheyuan Guo, Viktoriya LondonApurva Yeluru, Sindurathy Murugan, Karthikeyan Kandavelou, Nicolas Agier, Gilles Fischer, Kun Yang, J. Andrew Martin, Murat Bilgel, Pavlo Bohutski, Kristin M. Boulier, Brian J. Capaldo, Joy Chang, Kristie Charoen, Woo Jin Choi, Peter Deng, James E. DiCarlo, Judy Doong, Jessilyn Dunn, Jason I. Feinberg, Christopher Fernandez, Charlotte E. Floria, David Gladowski, Pasha Hadidi, Isabel Ishizuka, Javaneh Jabbari, Calvin Y.L. Lau, Pablo A. Lee, Sean Li, Denise Lin, Matthias E. Linder, Jonathan Ling, Jaime Liu, Jonathan Liu, Mariya London, Ma Henry, Jessica Mao, Jessica E. McDade, Alexandra McMillan, Aaron M. Moore, Won Chan Oh, Yu Ouyang, Ruchi Patel, Marina Paul, Laura C. Paulsen, Judy Qiu, Alex Rhee, Matthew G. Rubashkin, Ina Y. Soh, Nathaniel E. Sotuyo, Venkatesh Srinivas, Allison Suarez, Andy Wong, Remus Wong, Wei Rose Xie, Yijie Xu, Allen T. Yu, Romain Koszul, Joel S. Bader, Jef D. Boeke, Srinivasan Chandrasegaran

    Research output: Contribution to journalArticle

    Abstract

    Rapid advances in DNA synthesis techniques have made it possible to engineer viruses, biochemical pathways and assemble bacterial genomes. Here, we report the synthesis of a functional 272,871-base pair designer eukaryotic chromosome, synIII, which is based on the 316,617-base pair native Saccharomyces cerevisiae chromosome III. Changes to synIII include TAG/TAA stop-codon replacements, deletion of subtelomeric regions, introns, transfer RNAs, transposons, and silent mating loci as well as insertion of loxPsym sites to enable genome scrambling. SynIII is functional in S. cerevisiae. Scrambling of the chromosome in a heterozygous diploid reveals a large increase in a-mater derivatives resulting from loss of the MATα allele on synIII. The complete design and synthesis of synIII establishes S. cerevisiae as the basis for designer eukaryotic genome biology.

    Original languageEnglish (US)
    Pages (from-to)55-58
    Number of pages4
    JournalScience
    Volume344
    Issue number6179
    DOIs
    StatePublished - 2014

    ASJC Scopus subject areas

    • General

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  • Cite this

    Annaluru, N., Muller, H., Mitchell, L. A., Ramalingam, S., Stracquadanio, G., Richardson, S. M., Dymond, J. S., Kuang, Z., Scheifele, L. Z., Cooper, E. M., Cai, Y., Zeller, K., Agmon, N., Han, J. S., Hadjithomas, M., Tullman, J., Caravelli, K., Cirelli, K., Guo, Z., ... Chandrasegaran, S. (2014). Total synthesis of a functional designer eukaryotic chromosome. Science, 344(6179), 55-58. https://doi.org/10.1126/science.1249252