Saturday , January 23 2021

The first bacterial genome created entirely with a computer – ScienceDaily

All genome sequences of organisms known worldwide are stored in a database belonging to the National Center for Biotechnology Information in the United States. From today, the database has an additional record: Caulobacter ethensis-2.0. This is the first genome produced in the world of a living organism, developed by scientists at ETH Zurich. However, it must be emphasized, although the genome for it C. ethensis-2.0 was produced physically in the form of a very large DNA molecule, an equivalent organism does not yet exist.

C. ethensis-2.0 is based on a freshwater bacterium genome that has to study and harm it well, t Caulobacter Crescent, our bacteria occur naturally in spring water, rivers and lakes around the world. It doesn't cause any diseases. C. crescentus It is also a model organism commonly used in research laboratories to study the life of bacteria. The genome of this bacterium contains 4,000 genes. Previous scientists have shown that only about 680 of these genes are essential to the survival of the species in the laboratory. Bacteria with this smallest genome are viable under laboratory conditions.

Beat Christen, Professor of Experimental Systems Biology at ETH Zurich, and his brother Matthias Christen, a chemist at ETH Zurich, took the smallest possible genome of C. crescentus as a starting point. They chemically combined this genome from the start, such as a continuous circle-shaped chromosome. The task of this kind was seen as a true trip previously: The bacterial genome had been chemically synthesized presented by the American genetics pioneer Craig Venter in eleven years of work by 20 scientists, according to reports in the media. It is said that the cost of the project amounted to 40 million dollars.

Rationalize the production process

While the Venter team made an exact copy of a natural genome, the researchers at ETH Zurich changed their genome significantly using a computer algorithm. Their motivation was twofold: one, to make it much easier to produce genomes, and two, to get to grips with the basic questions of biology.

To create a DNA molecule as large as a bacterial genome, scientists must move forward in stages. In the case of the Caulobacter genome, the scientists at ETH Zurich synthesized 236 genome segments, and subsequently combined them. "The synthesis of these segments is not always easy," explains Matthias Christen. "DNA molecules have the ability to stick to other DNA molecules, but depending on the sequence, they can also turn themselves into loops and knots, which can interfere with the production process or make manufacturing impossible," explains Matthias Christen.

Simpler DNA sequences

In order to synthesise the genome segments in the simplest possible way, and then combine all the segments in the most simple manner, the scientists simplified the genome sequence significantly without adjusting the actual genetic information (at protein level). There is plenty of freedom for simplifying genomes, as biology has included redundancies for storing genetic information. For example, for many protein components (amino acids), there are two, four or more possibilities to write their information in DNA.

The algorithm developed by the scientists at ETH Zurich makes the best use of this redundancy of the genetic code. Using this algorithm, the researchers calculated the ideal DNA sequence for synthesising and building the genome, which was eventually used for their work.

As a result, the scientists have seduced many small adaptations to the smallest genome, which in their entirety, however, are striking: more than a sixth of each of the 800,000 DNA letters in the artificial genome were replaced, compared with the minimum "natural" genome. "Through our algorithm, we have rewritten our genome entirely into a new series of DNA letters that are no longer similar to the original sequence. However, the biological function at the protein level remains the same." kind, "says Beat Christen.

Litmus test for genetics

The genome has also been rewritten from a biological perspective. "Our method is a litmus test to see if biologists have a properly understood genetics, and allows us to highlight potential gaps in our knowledge," Beat Christen explains. Naturally, the genome can be rewritten containing only information that the researchers have understood. An additional "hidden" information that has been located in the DNA sequence, and that scientists have not yet understood, would have to be lost in the process of creating the new code.

For research purposes, scientists produced a strain of bacteria that included those naturally occurring. Caulobacter genome and also parts of the new artificial genome. By switching off certain specific genes in these bacteria, the researchers were able to test the functions of the artificial genes. They tested each of the artificial genes in a multi-skip process.

In these experiments, the researchers found that only about 580 of the 680 artificial genes were active. "With the information we received, however, it will be possible for us to improve our algorithm and develop a fully functional 3.0 genome version," Beat Christen said.

Huge potential for biotechnology

"Although the current version of the genome is not perfect yet, our work shows nevertheless that biological systems are compiled in such a simple way that we will be able to calculate the future; r design specifications on the computer according to our goals, and then build them, "Matthias Christen said. And this can be achieved in a relatively straightforward way, as Beat Christen emphasizes: "What took ten years with Craig Venter's approach, our small group achieved our new technology within the one-year time period with 120,000 manufacturing costs. Swiss franc. "

"We think it will also be possible to produce functional bacterial cells soon with a genome of such," Beat Christen said. There would be great potential for such a development. Possible future applications include synthetic micro-organisms that could be used in biotechnology for the production of complex pharmaceutical molecules or vitamins, for example. The technology can generally be used for all microorganisms, not just Caulobacter. Another possibility would be the production of DNA vaccines.

"As a promise as the research results and potential applications are, they call for an intense discussion in society about the purposes for which this technology can be used and, at the same time, about Abuses can be prevented, "Beat Christen said. It is still not clear when the first bacterium with artificial genome will be produced – but it is now clear that it can and will be developed. "We must use the time we have for intense discussion among scientists, and also in society as a whole. We are willing to contribute to that discussion, with all the information we have."

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