The First Computer-Generated

Bacterial Genome

Life has been recreated in the lab…synthetically. Scientists in Switzerland have created the world’s first fully computer-generated genome of a living organism with the help of a computer algorithm. The new bacterial genome, Caulobacter ethensis-2.0., has been added to the database of all known genome sequences belonging to the National Center for Biotechnology Information in the United States. The potential of biotechnology seems endless.

A Study to Create Synthetic Life

The biological blueprint of every living cell is stored within the DNA sequence of its genome. Traditional approaches in genetics have studied individual genes, yet rewriting -or creating- bacterial genomes through the process of chemical synthesis can help scientists understand how fundamental biological functions are encoded within a genome. Researchers at ETH Zurich developed an algorithm to compute the ideal DNA sequence for the synthesis and construction of the Caulobacter ethensis-2.0. genome, greatly simplifying the production of large DNA molecules that contain hundreds of genes. The process was detailed in the journal Proceedings of the National Academy of Sciences.

The Process

C. ethensis-2.0was synthesized based on the genome of a harmless freshwater bacterium, Caulobacter crescentus, which can be found in spring water, rivers and lakes all over the world. It does not cause any diseases and is often used in research to study the life of bacteria. Beat Christen, Professor of Experimental Systems Biology at ETH Zurich, and his brother, Matthias Christen, a chemist at ETH Zurich used C. crescentusas a starting point to chemically recreate the new bacterial genome as a continuous ring-shaped chromosome.

The genetic code allows DNA and RNA sequences to be “decoded” into the amino acids of a protein. In order to simplify the process of synthesis in this study, the scientists simplified the genome sequence without changing the genetic information. This is possible because many amino acids can be represented by more than one codon (sequences of nucleotides), meaning there are several different ways in which one amino acid can have its information written into DNA. In this study, scientists changed over 120,000 nucleotides and removed thousands of features that impede synthesis. The computer then redesigned the freshwater bacterium without changing the genetic information, using the algorithm to calculate the ideal sequence for the new genome.

“Through our algorithm, we have completely rewritten our genome into a new sequence of DNA letters that no longer resembles the original sequence. However, the biological function at the protein level remains the same,” says Beat Christen.

Bacterial Genome

A Sign of Progress

Scientists need to improve the algorithm developed for this study to include more essential elements to make the genome more functional. Only 81.5% of this new bacterial genome actually worked. Yet one of the most remarkable aspects of this research is how little time it took to create the new genome. The world’s first synthetic life form was created nearly ten years ago by Craig Venter and his team in an experimental feat that took 20 scientists more than 10 years and 40 million dollars to carry out. While Venter’s synthetic genome was an exact copy of a natural genome, the new research team at ETH Zurich changed the genome completely using the computer algorithm. The latest study took the work of 13 scientists just one year and $120,000 to complete.

This research shows that the process has become streamlined by making genomes shorter and simpler. It also shows that scientists may be able to produce whole, functional bacteria that may be used in the production of active DNA vaccines or in making molecules that can be used as pharmaceuticals or vitamins. This study is, thus, a giant step forward for the field of synthetic biology and shows how much progress has been made in the last few years. “Even though the current version of the genome is not yet perfect, our work nevertheless shows that biological systems are constructed in such a simple manner that in the future, we will be able to work out the design specifications on the computer according to our goals, and then build them,” says Matthias Christen.

Moral Implications

Advancements made in biotechnology have always been a subject of ethical concern. “As promising as the research results and possible applications may be, they demand a profound discussion in society about the purposes for which this technology can be used and, at the same time, about how abuses can be prevented,” says Beat Christen. While scientists still have to find a way to improve this particular algorithm before the first bacterium with an artificial genome is produced, it is only a question of time, time in which society must reflect on the future use of such advancements. Christen adds, “We must use the time we have for intensive discussions among scientists, and also in society as a whole. We stand ready to contribute to that discussion, with all of the know-how we possess.”

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