First Bacterial Genome Created Through a Computer – Review of Eurasia



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All genome sequences from organisms known all over the world are stored in a database belonging to the National Biotechnology Information Center in the United States.

As of today, the database has an additional entry: Caulobacter ethensis-2.0. It is the world's first genome of a living organism generated entirely by computer, developed by scientists of ETH Zurich. However, it should be emphasized that, although the genome of C. ethensis-2.0 was produced physically in the form of a very large DNA molecule, a corresponding organism does not yet exist.

C. ethensis-2.0 is based on the genome of a well-studied and harmless freshwater bacterium, Caulobacter crescentus,
which is a natural bacterium found in spring water, rivers
and lakes around the globe. It does not cause any disease. C. crescentus is also a model organism commonly used in research laboratories for
to study the life of bacteria. The genome of this bacterium contains 4,000
genes. Scientists have previously shown that only about 680 of these
Genes are crucial to the survival of species in the laboratory. Bacteria
with this minimal genome are feasible 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 minimum genome of C. crescentus as a starting point.
They set out to chemically synthesize this genome from scratch as a
chromosome in the form of a continuous ring. This task was previously seen as
true tour de force: The chemically synthesized bacterial genome
presented eleven years ago by pioneer of American genetics Craig Venter
was the result of ten years of work by 20 scientists, according to
reports. The cost of the project is said to have totaled 40
Millions of dollars.

Rationalizing the production process

While the Venter team made an exact copy of a natural genome, the
researchers at ETH Zurich have radically altered their genome using a
computer algorithm. Their motivation was twofold: one, to do much
easier to produce genomes, and two, to address key issues
biology.

To create a DNA molecule as large as a bacterial genome, scientists must proceed step by step. In case of Caulobacter genome, ETH Zurich scientists synthesized 236 segments of the genome,
which they subsequently joined. "The synthesis of these
segments is not always easy, "explains Matthias Christen. "DNA Molecules
not only have the ability to stick to other DNA molecules, but
depending on the sequence, they can also twist into loops and
us, which may hinder the production process or make the
impossible, "explains Matthias Christen.

Simplified DNA Sequences

Synthesize the segments of the genome in the simplest possible way, and
then join all segments in the simplest way, the
scientists radically simplified the genome sequence without modifying
the current genetic information (at the protein level). There are ample
latitude for the simplification of genomes, because biology was constructed
redundancies to store genetic information. For example, for many
protein components (amino acids), there are two, four or even more
possibilities of writing their information in DNA.

The algorithm developed by ETH Zurich scientists
optimal use of this redundancy of the genetic code. Using this
the algorithm, the researchers computed the ideal DNA sequence for the
synthesis and construction of the genome, which they used
for your work.

As a result, scientists have introduced many minor modifications in the
genome, which in their totality are, nevertheless, impressive: more
than one-sixth of all 800,000 DNA letters in the artificial genome
were replaced, compared to the "natural" minimum genome. "Through our
algorithm, we completely rewrite our genome in a new sequence
of DNA letters that no longer resemble the original sequence. Yet,
the biological function at the protein level remains the same, "says
Beat Christen.

Genetic Testing

The re-written genome is also interesting from a biological
perspective. "Our method is a decisive test to see if we biologists
have correctly understood genetics, and this allows us to highlight
possible gaps in our knowledge, "Beat Christen explains. Naturally, the
The rewritten genome may contain only information that the researchers
really understood. Additional "hidden" information that is
located in the DNA sequence, and has not yet been understood by
scientists, would have been lost in the process of creating the new
code.

For research purposes, the scientists produced strains of bacteria that contained both the Caulobacter genome and also segments of the new artificial genome. Turning off
certain natural genes in these bacteria, the researchers succeeded in
test the functions of artificial genes. They tested each of the
artificial genes in a multi-step process.

In these experiments, the researchers found that only about 580
of the 680 artificial genes were functional. "With the knowledge we have
gain, it will, however, be possible to improve our algorithm
and develop a fully functional 3.0 genomic version, "says Beat Christen.

Enormous potential for biotechnology

"Although the current version of the genome is still not perfect,
our work, however, shows that biological systems are built in
in such a simple way that we can solve the problem in the future.
design specifications on the computer according to our goals and then
build them, "says Matthias Christen. And this can be done in one
relatively simple form, as Beat Christen emphasizes: "What
took ten years with the approach of Craig Venter, our small group reached
with our new technology within one year with
manufacturing costs of 120,000 Swiss francs. "

"We believe that soon it will also be possible to produce
bacterial cells with such a genome, "says Beat Christen. Such
would have great potential. Among the possible futures
applications are synthetic microorganisms that could be used in
biotechnology for the production of complex pharmaceuticals
molecules or vitamins, for example. Technology can be employed
universally for all microorganisms, not only Caulobacter. Another possibility would be the production of DNA vaccines.

"As promising as the search results and possible applications can
In other words, they require a deep discussion in society about the
that this technology can be used and, at the same time, how
abuses can be avoided, "says Beat Christen. It is not yet clear when
the first bacterium with an artificial genome will be produced – but
Now it is clear that it can and will be developed. "We should use time
we have for intensive discussions between scientists and also in society
as a whole. We are ready to contribute to this discussion with all
the know-how we possess. "

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