All DNA sequences of life forms studied by scientists are stored in a database owned by the National Center for Biotechnology Information in the United States. And on April 1, a new entry appeared in the database: "Caulobacter ethensis-2.0". This is the world's first fully computer modeled and then synthesized synthetic genome of a living organism, developed by scientists from ETH Zurich (Swiss Institute of Technology Zurich). However, it should be emphasized that although the C. ethensis-2.0 genome has been successfully obtained as a large DNA molecule, the corresponding living organism does not yet exist.
The research work was carried out by Bit Kristen, professor of experimental systems biology, and his brother Matthias Kristen, a chemist. The new genome, called Caulobacter ethensis-2.0, was created by refining and optimizing the natural code of the bacterium Caulobacter crescentus, a harmless bacterium that lives in fresh water around the world.
More than a decade ago, a team led by geneticist Craig Venter created the first "synthetic" bacterium. In the course of their work, scientists synthesized a copy of the Mycoplasma mycoides genome, then it was implanted into a carrier cell, which after that turned out to be completely viable and retained the ability to reproduce itself.
The new study continues Kreiger's work. If earlier scientists created a digital model of the DNA of a real organism and synthesized a molecule based on it, the new project goes further using the original DNA code. Scientists significantly reworked it before synthesizing and testing its performance.
The researchers started with the original C. crescentus genome, which contains 4000 genes. As with any living organism, most of these genes do not carry any information and are "junk DNA". After analysis, the scientists concluded that only about 680 of them are needed to keep bacteria alive in the laboratory.
After removing the "junk DNA" and obtaining a minimal C. crescentus genome, the team moved on. The DNA of living organisms is characterized by the presence of built-in redundancy, which means that the synthesis of the same protein is encoded by different genes in several parts of the chain. The researchers replaced more than 1/6 of the 800 DNA letters in an optimization to remove redundant code.
βThanks to our algorithm, we have completely rewritten the genome into a new DNA letter sequence that no longer resembles the original,β says Beat Kristen, co-lead author of the study. βAt the same time, biological function at the level of protein synthesis remained unchanged.β
To test whether the resulting chain would work properly in a living cell, the researchers grew a strain of bacteria that had both the natural Caulobacter genome and artificial genome segments in its DNA. Scientists turned off individual natural genes and tested the ability of their artificial counterparts to perform the same biological role. The result was quite impressive: about 580 out of 680 artificial genes turned out to be efficient.
βWith the knowledge gained, we will be able to improve our algorithm and develop a new version of the 3.0 genome,β says Kristen. "We believe that in the near future we will create living bacterial cells with a completely synthetic genome."
At the first stage, such studies will help geneticists to verify the correctness of their knowledge in understanding DNA and the role of individual genes in it, since any mistake in the synthesis of the chain will lead to the fact that the organism with the new genome will die or be defective. In the future, they will lead to the emergence of synthetic microorganisms that will be created for predetermined tasks. Artificial viruses will be able to fight their natural counterparts, and special bacteria will produce vitamins or medicines.
The study was published in the journal PNAS.
Source: 3dnews.ru