Scientists discover the secrets to life with a microbe that has 473 genes

. A team of scientists created and synthesized a microbe using 473 genes. This self-replicating organism may help them understand how life began and developed in our world billions of year ago. Clyde A. Hutchison III (Professor Emeritus in Microbiology and Immunology, UNC-Chapel Hill) and his colleagues published their groundbreaking research in Science (citation below). This article outlines the breakthroughs in research that was published in 2010. It is the time when the first selfreplicating synthetic bacterial cell could be built and started up. It was demonstrated that it is possible to design genomes in a computer and then chemically make them in the laboratory. The synthetic genome can be transplanted in recipient cells in order to create new cells. 79 are the only 473 gene that has no functional group. They can also be broken down into four main groups. The team set out to create the smallest possible cell. This was the ultimate goal of the group. Their efforts will aid the scientific community to understand every function of every cell’s essential genes, the authors claim. The scientists used Mycoplasma to do their research. This genus is a group of bacteria which lacks a cell wall and has the fewest number of genes among all autonomously reproducing cells. The genome of Mycoplasma mecoides was synthesized six years ago by the team. Based on the existing literature, eight hypothetical genome segments were created by scientists. Each segment was tested to determine which genes are essential. The design-build-test process for designing a genome by using synthesis in yeast and cloning it in yeast. Viability testing is done by genome transplantation. Global transposon mutations are used to reevaluate gene essentiality after each cycle. (Image: science.sciencemag.org) During this design-build-test process, the scientists also tried to identify the genes required for robust growth but not absolutely vital for life – the quasi-essential genes. Professor Hutchison and J. Craig Venter (Ph.D.), Founder, Chairman and Chief Executive Officer at the J. Craig Institute created transposons, which are foreign genetic sequences, into several genes in order to alter their function and identify the essential ones for overall operation of bacteria. The group continued to experiment, shrinking the genetic code until the remaining genes were not affected. They discovered that many genes, initially considered non-essential at first, actually performed the same essential function of a second gene. Therefore, the minimum genome must contain one of these two genes. The creation of JCVI.0 with 473 genetics. They then created JCVI.0. The genome of this cell is much smaller than the current self-replicating cells we have seen. The minimal genome of this cell lacks most genes that encode lipoproteins and DNA-modifying genes. Comparison of JCVISyn1.0 (blue circles) and JCVISyn3.0(red circles), which shows the division into eight segments. The regions retained by JCVIsyn3.0 are indicated by the red bars within the blue circle. (Image: science.sciencemag.org) Contrastingly, nearly all the genes involved in reading and expressing the genetic information within the genome, as well as in preserving genetic data across generations, are retained. They don’t know the exact functions of 31% JCVI.0 genes. Many homologs were discovered in other organisms, however. These homologs could encode universal proteins with unknown functions. The scientists stated that the JCVI-syn3.0 platform is a powerful tool to study the core functions and life. A group of JCVI.syn3.0 cells showing spherical shapes of varying sizes. (Image: science.sciencemag.org) Many essential genes with unknown function Dr. Venter said regarding the number of essential genes: “Our attempt to design and create a new species, while ultimately successful, revealed that 32% of the genes essential for life in this cell are of unknown function, and showed that many are highly conserved in numerous species.” “All the bioinformatics studies over the past 20 years have underestimated the number of essential genes by focusing only on the known world. It is an important observation we will carry forward to the study of human genome.” Dr. Hutchison stated about the Science paper, “This paper represents over five years’ work by an amazing group of people. We want to create a cell that has the exact biological function of each gene. (Left: Clyde A. Hutchison; middle: J. Craig Venter, and Daniel G. Gibson. The citation is at the end of this page. Dr. Daniel G. Gibson is Vice President Synthetic Geneomics Inc. and Associate Professor at J. Craig Venter Institute. He said that this paper represents a significant step towards our ability to create and construct synthetic organisms starting from scratch with predictable results. The tools and knowledge gained from this work will be essential to producing next generation production platforms for a wide range of disciplines.” This work was funded by Synthetic Genomics, Inc., the J. Craig Venter Institute endowment, and the Defense Advanced Research Projects Agency’s Living Foundries program, HR0011-12-C-0063. Citation: “Design & synthesis of minimal bacterial genes,” Clyde A. Hutchison III. Ray-Yuan Chuang. Nacyra A. Assad-Garcia. Thomas J. Deerinck. Mark H. Ellisman. John Gill. Krishna Kannan. Bogumil J. Karas. Li Ma. James F. Pelletier. Zhi-Qing Qi. R. Alexander Richter. Elizabeth A. Strychalski. Lijie Sun. Yo Suzuki. Wise. Wise. Wise. Wise. Wise. Glass, Chuck Merryman1 and J. Craig Venter Science. 25 October 2016. DOI: 10.1126/science.aad6253. Video – JCVI.0: Minimal cell These time-lapse videos show the minimal cells (JCVI.0), and the wild-type organism (JCVI.1.0). The footage is magnified 1500X and shows how the bacteria grows over 8 hours.

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