The 覃 heavy army team (the first one is Qi Zhongjun) and the students in the Key Laboratory of Synthetic Biology of the Institute of Molecular Plants of the Chinese Academy of Sciences / Plant Bioecology (photo taken on July 31). Xinhua News Agency
The Economic Daily reported on August 11 that he and the idol's “reunion” were a bit unique to the Chinese Academy of Sciences Institute of Excellence in Molecular and Plant Science/Institute of Plant Physiology and Ecology. On August 2nd, the world's top academic journal Nature, “back to back”, published two online results on yeast chromosomes, one from the team of the 覃 heavy army, and the other from the yeast chromosome synthesis field “ veteran” ;—— American Academy of Sciences Jeff · Boyk.
The difference is that this time, the heavy army team is one step ahead, and for the first time in the world, artificially created a simple life that does not exist in nature — — yeast eukaryotic cells containing only a single chromosome. “This achievement has enabled the world to understand that life forms can be simplified through manual transformation. It also means that the boundaries of natural life can be artificially broken, and even artificially create new life that does not exist in nature. & rdquo; 覃 heavy army explained.
Artificial synthesis of eukaryotes containing only a single chromosome
The living organisms in nature are roughly divided into two categories, one is a nucleus whose nucleus is surrounded by a nuclear membrane, such as humans, animals, plants, fungi, and yeast; the other is a prokaryotic organism with a chromosome-exposed non-nuclear membrane, such as bacterial. In the long evolutionary process of nature, different living organisms have gradually formed their own unique genomes, including a relatively fixed number of chromosomes.
However, the number of chromosomes carrying the genetic information of growth and reproduction of living organisms varies from species to species: humans have 23 pairs of chromosomes, 24 pairs of close relatives, 20 pairs of mice, and 4 pairs of fruit flies … … The number of chromosomes is uneven? Does the specific number of chromosomes provide a certain advantage for a particular species? These unknowns, which are related to the essence of life, have also aroused the curiosity of the heavy army.
“Does eukaryotes with multiple linear structural chromosomes, like prokaryotes, load all genetic material with a single chromosome and achieve normal cell function? ”“Can a man-made eukaryote containing a single chromosome be made to have normal cellular functions? & rdquo; These bold ideas have been hovering in the minds of the heavy army for a long time, and finally put into practice.
覃重军's “whimsical” is not without scientific basis. In 2010, American scientist Craig ·, who led the Human Genome Project; Venter and his research team reported in the journal Science that the world's first "artificial life" —— contains all chemical synthesis The genomically controlled prokaryote —— mycoplasma, which is almost identical to the natural chromosomal sequence, caused a sensation. Coincidentally, in 2017, the United States University of New York University Lange Medical Center Jeff · Professor Boyk led a global collaboration group including the Chinese team, completed the chemical synthesis of 5 chromosomes of Saccharomyces cerevisiae, successfully provided the first Two empirical evidences.
The goal has been set, and the heavy army will lock the test object on Saccharomyces cerevisiae. In the face of many eukaryotes, the reason why the small Saccharomyces cerevisiae is selected instead of others is that there are two considerations: one is that one-third of the genes in Saccharomyces cerevisiae are homologous to human genes; the other is that compared to other animals and plants, S. cerevisiae has a clearer genetic background and is more convenient to operate.
“As a model of single-cell eukaryotes, if scientists have new discoveries on Saccharomyces cerevisiae, relevant research results may be extended to higher plants and animals. & rdquo; 覃 heavy army said.
Gene & ldquo; magic cut & rdquo; & mdash; & mdash;
Cut out redundant repeat gene information
Yeast is an important model material for studying chromosomal abnormalities. It has been studied by tens of thousands of scientists all over the world for more than half a century. However, in 2013, with the trial started, “Synthetic single-chromosome yeast”? Hey teacher, you are crazy! & rdquo; Such doubts are coming.
“With no daring conjecture, there is no great discovery. ” Faced with the doubts and cold eyes of outsiders, this sentence of the military used Newton repeatedly warned himself. At that time, Yan Zhongjun did not know, another corner of the world, Jeff · Boyk also began research on yeast chromosome fusion.
Ideal is full, the reality is very skinny. Take chromosome fusion as an example. A complete eukaryotic linear chromosome, usually containing a centromere for chromosome segregation and two telomeres for protecting the ends of chromosomes. In order to achieve the fusion of two chromosomes, it is necessary not only to remove the two telomeres of the two chromosomes, but also to remove the centromeres of one of the two chromosomes, thereby ensuring that the chromosomes are normal during cell division. Separation. How to do? Without any experience, Yu Qiang led the research team to cross the river by feeling the stones.
16 chromosomes changed 15 times, changed 14 pieces, changed 13 pieces …… time is not affectionate, 4 years of hard work, 15 rounds of chromosome fusion, the 覃 heavy army team finally succeeded in creating a Saccharomyces cerevisiae with only one linear chromosome Nuclear cells & mdash; & mdash; Saccharomyces cerevisiae strain SY14. This is also the first artificial single-chromosome eukaryotic cell in the world.
What is the follow-up performance of this synthetic “new life”? The research team of Qiu Junjun further cooperated with the research group of Academician Zhao Guoping of the Key Laboratory of Synthetic Biology, the research group of Zhou Jinqiu Researcher of the Institute of Biochemistry and Cell Biology of the Chinese Academy of Sciences, and the team of Fraser Gene Information Company to further identify the metabolic physiology and reproductive function of SY14. , and the three-dimensional structure of its chromosomes. The results show that although the three-dimensional structure of the artificially created single-chromosome yeast has undergone great changes, it still has normal cell functions.
In other words, the Saccharomyces cerevisiae obtained by artificially synthesizing 16 natural chromosomes carried by Saccharomyces cerevisiae into a single large chromosome with function, although the chromosome structure has changed greatly, the cell growth is exactly the same, and the functions are almost the same. . From the perspective of basic research, this is a simple creation of a living body. “This result subverts the traditional notion that the three-dimensional structure of chromosomes determines the spatiotemporal expression of genes, and thus reveals a new relationship between the three-dimensional structure of chromosomes and the realization of cell life functions. & rdquo; 覃 heavy army said.
“Jeff · In the final step of the fusion of two chromosomes into one, the Boyk team was unable to obtain cells with only one chromosome, and eventually only obtained yeast with two chromosomes. "There is a lot of speculation, perhaps because Jeff · the Boyk team did not delete many of the repetitive sequences on the chromosomes, and the squadron's research team used the gene "Magic Scissors" to boldly cut out redundant repetitive gene information in many chromosomes. So that the chromosomes can become more stable when they are fused.
Open the door to artificial life
Telomere is a protective structure at the end of a linear chromosome. Experiments have shown that as the number of cell divisions increases, the length of telomeres gradually decreases. When telomeres become shorter, cells die, and premature aging of humans Tumor formation and so on are closely related to telomere shortening of chromosomes. “Compared to the 32 telomeres of natural yeast, our synthetic single linear chromosome has only 2 telomeres, which is simpler and more intuitive, which provides a good model for studying human telomere function and cell senescence. & rdquo; 覃 heavy army said.
Nature reported that the series of chromosome-converted strains established in this study are of great value in studying the relationship between telomere biology, centromere biology, meiotic recombination, and nuclear structure and function. Paul ·, Director of Natural Science China; Evans believes that this "Nature" paper is completed independently by Chinese scientists, showing China's efforts and achievements in establishing a sustainable scientific research ecosystem, as well as exploring the origin of life. A new direction has been opened up with major fundamental science issues such as evolution.
Shen Yi, director of the Department of Life Sciences at the Frontier Science and Education Bureau of the Chinese Academy of Sciences, sees that the artificially complex yeast chromosomes are presented in a completely new form through artificial transformation, which is a major after the proto-nuclear bacteria < artificial life. breakthrough. The birth of single-chromosome yeast, together with the full-synthesis of yeast chromosomes involved in Chinese scientists, is followed by the synthesis of crystalline bovine insulin and tRNA (yeast alanine-transferred ribonucleic acid) in the 1960s. The use of synthetic science strategies to answer major fundamental questions in the life sciences is a vivid manifestation of the concept of synthetic biology, and opens up new directions for human studies of the nature of life.
Of course, performance is not perfect. Yan Zhongjun frankly said that the chromosomal strains after fusion showed small adaptive limitations and sexual reproduction defects, and these findings may help explain the advantages of having more chromosomes. “ Single-Chromosome Yeast & Birth & rsquo; opened the door to artificial life for us. Just like the trains that humans first made, they may not run as fast as horse-drawn carriages, but with the advancement of technology, these problems can be solved one by one. & rdquo; 覃 heavy army said.
(The original title is "China's scientists for the first time in the world created a simple life in the natural world does not exist in the simple life & mdash; & mdash; artificial yeast birth")