Murat Bilgel, Ph.D.

Murat Bilgel, Ph.D.

Associate Scientist at the Brain Aging and Behavior Section, Laboratory of Behavioral Neuroscience, National Institute on Aging. All views are my own.

Total synthesis of a functional designer eukaryotic chromosome

Published in Science, 2014

Narayana Annaluru, Héloïse Muller, Leslie Mitchell, Sivaprakash Ramalingam, Giovanni Stracquadanio, Sarah Richardson, Jessica Dymond, Zheng Kuang, Lisa Scheifele, Eric Cooper, Yizhi Cai, Karen Zeller, Neta Agmon, Jeffrey Han, Michalis Hadjithomas, Jennifer Tullman, Katrina Caravelli, Kimberly Cirelli, Zheyuan Guo, Viktoriya London, Apurva Yeluru, Sindurathy Murugan, Karthikeyan Kandavelou, Nicolas Agier, Gilles Fischer, Kun Yang, J Martin, Murat Bilgel, Pavlo Bohutski, Kristin Boulier, Brian Capaldo, Joy Chang, Kristie Charoen, Woo Choi, Peter Deng, James DiCarlo, Judy Doong, Jessilyn Dunn, Jason Feinberg, Christopher Fernandez, Charlotte Floria, David Gladowski, Pasha Hadidi, Isabel Ishizuka, Javaneh Jabbari, Calvin Lau, Pablo Lee, Sean Li, Denise Lin, Matthias Linder, Jonathan Ling, Jaime Liu, Jonathan Liu, Mariya London, Henry Ma, Jessica Mao, Jessica McDade, Alexandra McMillan, Aaron Moore, Won Oh, Yu Ouyang, Ruchi Patel, Marina Paul, Laura Paulsen, Judy Qiu, Alex Rhee, Matthew Rubashkin, Ina Soh, Nathaniel Sotuyo, Venkatesh Srinivas, Allison Suarez, Andy Wong, Remus Wong, Wei Xie, Yijie Xu, Allen Yu, Romain Koszul, Joel Bader, Jef Boeke, Srinivasan Chandrasegaran, "Total synthesis of a functional designer eukaryotic chromosome." Science, 2014.


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.

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