First computer-generated genome could lead to custom synthetic lifeforms
Scientists at ETH Zurich have created the first fully computer-generated genome of a living organism. The brand new genome, named Caulobacter ethensis-2.0, was built by essentially cleaning up and simplifying the natural code of a bacterium called Caulobacter crescentus. For now it exists as one large DNA molecule and not a living organism itself, but the team says this is a huge step towards creating completely synthetic life and medicinal DNA molecules.
Over a decade ago, a team led by geneticist Craig Venter created the first "synthetic" bacterium, which was basically a digital copy of the Mycoplasma mycoides genome. That was then implanted into recipient cells and found to be a viable version of the real creature, even being able to self-replicate.
The new study builds off that prior work, and goes a step further towards completely synthetic life. If the earlier creation was a digital remake of a real organism, the new project is a remix – the team took what works with the original and fine-tuned it to be more efficient.
The researchers started with the C. crescentus genome, which naturally contains 4,000 genes. Like most organisms, the majority of those genes are "junk DNA," and scientists have previously found that only about 680 of them are necessary for life. That "minimal genome" has been found to be enough to keep bacteria alive in the lab.
From the minimal genome of C. crescentus, the team then pared it back even further by trimming out the built-in redundancies. In many cases, amino acids can be assembled in several different combinations to achieve the same effect, so the team developed an algorithm to figure out the ideal DNA sequence. In the end, the researchers replaced more than a sixth of the 800,000 DNA letters in the minimal genome.
"Through our algorithm, we have completely rewritten our genome into a new sequence of DNA letters that no longer resembles the original sequence," says Beat Christen, co-lead author of the study. "However, the biological function at the protein level remains the same."
To test whether these edits would still function properly, the researchers then engineered bacteria that had both the natural Caulobacter genome and segments of the artificial one. They turned off some of the natural genes and checked whether the artificial ones stepped in to do the same job. And their success rate was pretty good, with about 580 of the 680 artificial genes proving functional.
"With the knowledge we have gained, it will, however, be possible for us to improve our algorithm and develop a fully functional genome version 3.0," says Christen. "We believe that it will also soon be possible to produce functional bacterial cells with such a genome."
Eventually, this kind of work could lead to synthetic microorganisms that can be created for very specific purposes. DNA vaccines could be synthesized, as could organisms that produce vitamins and drugs.
The research was published in the journal PNAS.
Source: ETH Zurich
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