Scientists at ETH Zurich have produced the first fully computer-generated genome of a living organism. The genome corresponds to a theoretical organism called Caulobacter ethensis-2.0, which does not yet exist beyond the form of a very large DNA molecule. Details of the study were published in the Proceedings of the National Academy of Sciences.
In 2008, a chemically synthesized genome was produced by the geneticist Craig Venter. This genome was an exact copy of a natural genome and was the result of ten years work by 20 scientists. The cost to produce the genome was said to have totaled 40 million dollars.
In this case, the researchers based their C. ethensis-2.0 genome on a well-studied, harmless freshwater bacterium called Caulobacter crescentus. This bacterium does not cause any disease and is frequently used as a model for studying bacteria. The C. ethensis-2.0 genome was radically altered using a computer algorithm and thus not an exact copy like Venter’s genome.
To create their DNA molecule as a bacterial genome, the researchers synthesized 236 genome segments, which they pieced together. To make things easier, they simplified the genome sequence without modifying genetic information at the protein level. They did this by taking advantages of redundancies in the genetic code, using an algorithm to compute the ideal DNA sequence for synthesis and construction. Though this process more than a sixth of all the 800,000 DNA letters in the artificial genome were replaced compared to the natural genome.
The researchers see many applications for this work. Creating an artificial genome can serve as a method of testing understanding of genetics since rewritten genomes can only include information that researchers know. Gaps in function would indicate a previously unknown function of certain genetic code.
The research could also have applications in biotechnology. "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, one of the lead study authors. What’s more, this project was completed within the time frame of one year at a cost of 120,000 Swiss francs.
The researchers believe that this technology may someday enable the creation of synthetic microorganisms that could do things like produce pharmaceutically active molecules or vitamins.
Image: Caulobacter crescentus is a harmless bacterium living in fresh water throughout the world (electron microscope image). Image courtesy of ETH Zurich.