A research team headed by Prof. Qin Zhongjun and his collaborators from the Key Laboratory of Synthetic Biology, CAS Center for Excellence in Molecular Plant Sciences, Shanghai Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, has artificially created a eukaryotic cell with a single chromosome for the first time in the world. The result, a milestone breakthrough in the field of synthetic biology, was published in Nature on August 2.

Can humans create life? In 2010, an American scientist J. Craig Venter and his research team reported the first "artificial life" - a prokaryotic mycoplasma driven by a chemically synthesized genome -- in Science. It was quite similar to the native chromosomal sequences, and caused a sensation. This time, the research team led by the Qin research group created an artificial functional single-chromosome eukaryotic Saccharomyces cerevisiae from its native sixteen chromosomes. This work shows that natural complex life systems can be reduced by human intervention, and the boundaries of natural life can be artificially broken, and a new life that does not exist in nature can be artificially created.

Biology textbooks elaborate that living organisms that exist in nature are divided into eukaryotes with nuclear membrane-wrapped chromosomal nuclei and prokaryotic organisms surrounded by naked nuclear membranes. Chromosomes carry genetic information about the growth and reproduction of living organisms. Eukaryotes usually contain multiple chromosomes in a linear structure, while prokaryotes usually contain a chromosome of a circular structure. In his study, Prof. Qin Zhongjun hypothesized that eukaryotes can be artificially created like a prokaryote, which organize all genetic material in a single linear chromosome and can carry out the normal cellular functions. Qin and his colleague Xue Xiaoli customized the artificial single-chromosome yeast with “engineering precision design”, and established the guiding principles and rational experimental design of the overall program. Ph.D. student Shao Yangyang has been developing an efficient chromosome fusion method since 2013. After 4 years of chromosome fusion, a Saccharomyces cerevisiae strain SY14 with only one linear chromosome was successfully created.

Since then, Qin Zhongjun's research team has further cooperated with Zhao Guoping’s research team from the National Key Laboratory of Synthetic Biology, Zhou Jinqiu’s research group from the Institute of Biochemistry and Cell Biology of the Chinese Academy of Sciences, Wuhan Frasergen Gene Information Co., Ltd. and Zhao Zhihu from the Academy of Military Medical Sciences, to perform in-depth identification of the metabolic, physiological and reproductive functions of SY14 and the three-dimensional structure of its chromosomes. This study found that although the three-dimensional structure of the artificially created single linear chromosome has undergone great changes, the SY14 yeast cell has normal cellular functions, which subverts the traditional concept of chromosome three-dimensional structure determining the spatiotemporal expression of genes, and reveals a new relationship of the chromosomal three-dimensional structure and cell functions.

This research achievement is a new example of exploring major fundamental scientific issues in the origin and evolution of life, based on "hypothesis-driven" classical molecular biology and the "engineering research model" of synthetic biology. The natural complex yeast chromosome was transformed into a new and simplified form through artificial engineering, which is a major breakthrough after the “artificial life” of prokaryotic bacteria. The "birth" of single-chromosome yeast, together with the full synthesizing of yeast chromosomes that Chinese scientists are involved in, are achievements to add to the synthetic synthesis of bovine insulin and tRNA in the 1960s. Chinese scholars are once again using synthetic science strategies to answer a question in the field of life sciences. A major fundamental issue is the establishment of a bridge between genomic evolution of prokaryotes and eukaryotes. This is a vivid manifestation of the concept of “construction and knowledge” in synthetic biology, which has opened up a new direction for human beings to study the essence of life.

Saccharomyces cerevisiae is an important model for studying chromosomal abnormalities, and 1/3 of the genes are homologous to human with 23 pairs of chromosomes. Telomeres are protective structures at the ends of linear chromosomes. As the number of cell divisions increases, the length of the telomeres gradually decreases, and when the telomeres become too short, the cells die. Premature aging in humans is directly related to the telomere length of the chromosome. In addition, shortening of telomeres is also associated with many diseases such as genetic mutations and tumor formation. Compared with the 32 telomeres of natural yeast, the single linear chromosome yeast created by Prof. Qin Zhongjun’s research team, which has only two telomeres, is a good model for studying telomere function and cell senescence.

The research was funded by the Chinese Academy of Sciences' strategic pilot science and technology project "Molecular mechanism and regulation of cell fate plasticity", as well as the National Natural Science Foundation and the Ministry of Science and Technology.

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Prof. Qin Zhongjun


Source: CAS Center for Excellence in Molecular Plant Sciences/Shanghai Institute of Plant Physiology and Ecology (SIPPE)

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