As a eukaryote, a category that includes humans and other animals, S. cerevisiae has a more complex genome than Venter's parasite. The synthetic yeast chromosome — which has been stripped of some DNA sequences and other elements — is 272,871 base pairs long, representing about 2.5% of the 12-million-base-pair S. cerevisiae genome.The researchers, who report their accomplishment in Science1, have formed an international consortium to create a synthetic version of the full S. cerevisiae genome within 5 years.
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Total Synthesis of a Functional Designer Eukaryotic Chromosome
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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