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Sc3.0: revamping and minimizing the yeast genome
Genome Biology ( IF 10.1 ) Pub Date : 2020-08-13 , DOI: 10.1186/s13059-020-02130-z Junbiao Dai 1 , Jef D Boeke 2 , Zhouqing Luo 1 , Shuangying Jiang 1 , Yizhi Cai 1, 3
Genome Biology ( IF 10.1 ) Pub Date : 2020-08-13 , DOI: 10.1186/s13059-020-02130-z Junbiao Dai 1 , Jef D Boeke 2 , Zhouqing Luo 1 , Shuangying Jiang 1 , Yizhi Cai 1, 3
Affiliation
* Correspondence: junbiao.dai@siat. ac.cn; yizhi.cai@manchester.ac.uk CAS Key Laboratory of Quantitative Engineering Biology, Guangdong Provincial Key Laboratory of Synthetic Genomics and Shenzhen Key Laboratory of Synthetic Genomics. Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China Full list of author information is available at the end of the article Recent improvements in DNA synthesis and editing techniques enable engineering the entire genome of an organism, offering new tools to directly probe relationships between genotype and phenotype. Genome synthesis potentially allows the researchers to gain a much greater degree of control of an organism, and it also leads to a completely new way to understand the biology of genomes. In 2008, the first mega-size bacteria genome was built from oligonucleotides [1]. Next, the 4-Mb genome of E. coli was redesigned and engineered [2, 3]. More recently, the synthesis of first eukaryotic genome, the 12-Mb Saccharomyces cerevisiae genome, is nearing completion as the goal of the Sc2.0 initiative [4] and Genome Project-Write (GP-Write) has been proposed to engineer higher eukaryotes with gigabase-sized genomes [5]. As genome sizes increase, the design principles of synthetic genomes are becoming more sophisticated and complex. In the first synthetic genome, the Mycoplasma genome, only few watermarks were introduced [1]. The nearly completed Sc2.0 project involves building a genome that is heavily modified [4]. These modifications include the removal of all retrotransposons, subtelomeric repeats, and introns; eliminating and relocating all tRNA genes; swapping all TAG stop codon to TAA; and introducing numerous PCRTags (a type of watermark) by synonymous recoding of coding sequences. More importantly, over 4000 LoxPSym sites need to be inserted in the 3′ UTR of all non-essential genes, as well as at synthetic “landmarks,” a system designated as “synthetic chromosome rearrangement and modification by loxP-mediated evolution” (SCRaMbLE [6]). Overall, the native genome will be reduced in size by about 8% with an aim to reduce genomic contents and stabilize the genome, while still maintaining similar 3D structures and functions as wild-type chromosomes. One thing we learned while constructing new chromosomes is that despite the variety of changes introduced, cells are quite tolerant to these perturbations. For example, the relocation of the megabase-size, highly repetitive ribosomal gene cluster on chrXII to a much smaller chromosome, chrIII, conferred only very minor, if any, effects on cell growth [7]. These results lead us to propose a new hypothesis that the yeast genome contains a larger variety of redundant elements. Therefore, more radical changes might be introduced to generate a much more compact genome. Here, we present a proposal to design and synthesize the next version of the synthetic yeast genome, dubbed Sc3.0.
更新日期：2020-08-13
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