Unprecedented! The world's top academic journal "Science" published at 3:00 a.m. Beijing time on March 10th published the 4 research papers of Chinese scientists in the form of a cover. (Note: Each issue of "Science" magazine will select the current period. A heavy research result as a cover and cover title.)
Representatives of Chinese scientists, from left to right, are Li Bingzhi, Dai Junyi, Yang Huanming, Yuan Yingjin, and Shen Yu.
The four long articles completed by Tianjin University, Tsinghua University, and BGI have introduced the latest breakthroughs in biosynthetic research: completed the design and chemical synthesis of four eukaryotic Saccharomyces cerevisiae chromosomes—you know, Yeast has a total of 16 chromosomes, which was discovered by international colleagues after years of struggle.
In the process of synthesizing chromosomes, they also broke through a number of key core technologies in biosynthesis, such as the breakthrough in the inactivation of cells caused by synthetic genomes, the design and construction of chromosomal circadian disease models, and the development of long chromosome-grading assembly strategies. Artificially designed synthetic genomes have the flexibility to add, subtract, and so on. These technologies will help show the world's life science research and related practical applications. Its value is invaluable.
Domestic and foreign counterparts pointed out that this is another milestone breakthrough after the synthesis of prokaryotes, which is expected to open a new era of human “design life, recreate life, and reshape lifeâ€.
Synthetic yeast chromosome, what's the point?
Academician Yang Huanming, who is the director of the Huada Gene, who has participated in the Human Genome Sequencing Project, said that Synthetic Biology is the third largest source of genome design synthesis following the DNA Double Helix Discovery and the Human Genome Sequencing Project. Secondary biotechnology revolution. He pointed out that the most important classification basis in the biological community is neither plants nor animals, nor multicellular or unicellular organisms, but differentiated by prokaryotes and eukaryotes. “The genomes of prokaryotes such as bacteria and viruses are relatively simple, and the genes (DNA) of eukaryotic organisms such as animals, plants, fungi, etc. are both rich and complex and usually contain hundreds of millions to even billions of base pairs of information. DNA as a genetic material is usually assigned to different chromosomes, and these chromosomes are buried deep in specific regions of the nucleus.So, synthesizing a genome of a eukaryotic organism is a very difficult task, but if biology actually does To lead the technological revolution, the synthesis of eukaryotic genome technology will play a very central role."
To complete the design and chemical reproduction of the complete Saccharomyces cerevisiae genome, the international scientific community launched the Saccharomyces cerevisiae Gene Assembling Project (Sc2.0 Project), which is a landmark international cooperation project for synthetic genomics research. This project was initiated by Jeff Burke, an academician of the American Academy of Sciences, and participated in and coordinated with multinational research organizations from the United States, China, the United Kingdom, France, Australia, and Singapore to try to redesign and synthesize all 16 chromosomes of Saccharomyces cerevisiae (about 12 Mb in length). 1Mb is megabase pairs).
Yuan Yingjin, a professor at the Tianjin University’s School of Chemical Engineering, was the first Chinese scientist to participate in the project. He published two papers as a correspondent author in the “Science†journal. He told reporters that fruit fly, zebrafish, and Saccharomyces cerevisiae, which are often used in scientific experiments, are "model eukaryotic unicellular organisms" in biological research. "If the synthesis of viral genomes opens up the study of genomic chemical synthesis, then the combination of prokaryotic and eukaryotic genes into continuous breakthroughs in research has preliminarily achieved the control of the life cycle of unicellular prokaryote and eukaryote by chemically fully synthetic genomes." Saccharomyces cerevisiae is the first eukaryote to be sequenced by the whole genome. Designing and reconstructing the yeast genome on a large scale is a direct test of the authenticity, integrity, and accuracy of knowledge storage in the yeast field. Chemical synthesis of yeast can, on the one hand, help humans understand more fundamental biological problems. On the other hand, through the genomic rearrangement system, yeast can be rapidly evolved and can be obtained in the fields of medicine, energy, environment, agriculture and industry. Important application potential strains. â€
What do scientists in our country find in synthetic yeast?
In 2014, Sc2.0 has created a single artificial yeast chromosome. In this international cooperation, Chinese and foreign scientists completed the synthesis of five chromosomes, of which four were completed by Chinese scientists and accounted for 66.7% of the completed number. The Sc2.0 plan has taken a big step forward.
Among them, Yuan Yingjin led the Tianjin University team to complete the chemical synthesis of chromosomes 5 and 10 (synV and synX) and developed efficient chromosomal defect target localization techniques and chromosomal point mutation repair techniques; Dr. Dai Junsheng leads Tsinghua University The team completed the synthesis of the longest chromosome 12 (synXII) in the currently synthesized chromosome; the team of Shenzhen Huada Gene Research Institute teamed up with the University of Edinburgh to complete the synthesis and deep genotype-phenotype of chromosome 2 (synII) Correlation Analysis.
“The continuous increase in the scale and complexity of synthetic genomes poses a growing challenge to the scientific community's understanding of the way organisms operate and the nature of life. A major challenge facing DNA synthesis at the genome level is Localize the sequences that affect the growth of cells in the artificial genome, that is, bugs. There are three methods for routine troubleshooting, which are time consuming, inefficient, and inefficient.†Yuan Yingjin team member, “No. 10 The first author of the chromosome, Wu Yi, a doctoral student at Tianjin University, said: In the process of synthesizing a 770 kb (kb: kilobase pair) Saccharomyces cerevisiae 10 chromosome, we created a rapid target for genomic defects and accurate The repair method solves the problem of the inactivation of cells caused by the fully chemically synthesized genome. The whole synthetic yeast chromosome we have has complete vitality, can successfully regulate the growth of yeast, and has a variety of environmental responsiveness. This method is universal in chemical synthesis genome research and as a novel phenotypic and genomic association analysis strategy, it is expected to significantly enhance our knowledge of genome structure and function. â€
Xie Zexiong, a doctoral student at Tianjin University who was the first author of the "Chromosome 5" article, said that in the overall promotion of the Sc2.0 program, we have established a genome-based precise repair technique and a DNA large fragment repeat repair technique based on the co-transformation of multiple target fragments. It solves the problem of precise synthesis of long artificial DNA fragments. At the same time, for the first time, we have completely matched the synthetic sequence of eukaryotic artificial genome with the design sequence, systematically supporting and evaluating the current design principles of eukaryotes. The breakthrough of this technology lays the foundation for the study of the redesign, functional verification and technological improvement of artificially designed genomes. The use of chemically synthesized yeast chromosome 5 customization to establish a set of ring chromosome model, through the design of specific artificial watermarks to achieve the tracking of chromosome changes in the process of cell division and analysis, in order to study the current irreversible ring chromosome disease Mechanisms and potential treatments for cancer, aging, etc. provide research models. In addition, we have developed a multi-level modular and standardized gene assembly method, created a one-step large-scale assembly technique and a parallel chromosome synthesis strategy, and achieved custom precision synthesis from small nucleotides to living eukaryotic chromosomes. â€
Tsinghua University's Dai Junmin team designed and synthesized chromosome 12 In the study, they developed strategies for the assembly of long-length chromosomes, that is, firstly by stepwise synthesis of the endogenous DNA in different regions of the chromosome by means of large-fragment synthetic sequences, and then using the yeast meiosis process. The characteristics of homologous recombination combine the synthetic sequences of multiple strains to obtain a complete synthetic chromosome. The highly repetitive ribosomal RNA coding gene clusters present on chromosome 12 were deleted and engineered, and the ribosomal RNA coding gene clusters were reconstructed at multiple sites in the genome using the modified repeat units. "This work laid the foundation for the design and preparation of other ultra-complex, ultra-complex genomes in the future. It also demonstrated that the rDNA (ribosomal DNA) region and other sequences in the yeast genome are surprisingly flexible and malleable." Indicated.
Shenzhen Huada Gene Research Institute and the University of Edinburgh jointly completed the de novo design and total synthesis (length 770 Kb) of chromosome 2. Synthetic yeast strains exhibited a highly similar life activity to that of wild type. The first author of the paper, Shen Yan, head of Shenzhen National Gene Bank synthesis and editing platform, said that researchers use the “Trans-Omics†method from phenotype, genome, transcriptome, proteome and metabolism. The genotype-phenotype in-depth correlation analysis was systematically performed at five levels of the group, demonstrating that the artificially designed and synthesized Saccharomyces cerevisiae genome can be increased or deleted with a high degree of flexibility. â€
It is gratifying that the yeast strains synthesized by BGI and Edinburgh University not only have a highly similar life activity to that of the wild type, but also greatly enhance their adaptability to the environment, and their evolutionary speed has increased geometrically.
Synthesis of four yeast chromosomes, value geometry?
"With the human genome sequencing announced in 2000, China has only undertaken one percent of the work. This time we completed a quarter of the chromosome synthesis of Saccharomyces cerevisiae, which is arguably China's breakthrough achievement in the field of synthetic biology. This has further established China’s international status in this area.†Yang Huanming said, “Comparing the two, it is not difficult to see that we have made great progress in the field of life science research. In the study of Saccharomyces cerevisiae design and synthesis, we have 'Switching to 'and running', it is not impossible to lead in the future."
(Original title: Unprecedented! Chinese scientists 4 papers on the cover of "Science")
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