US researchers have engineered a
bacterium whose genetic material includes DNA or bases not found in nature
Deoxyribonucleic acid (DNA) is the famous double helix discovered by Watson and
Crick in the 1950s and commonly known as the carrier of the
“genetic code” of life. It’s found in all living things on Earth, from the
smallest cells to the largest redwood trees, and in
each and every one of these organisms the basic DNA structure is exactly the
Though the models of DNA that are on display in museums seem impossibly complex,
it is actually a very simple molecule. It’s twisty double
backbone of phosphates and sugars carries branches that link the
two spirals together like steps in a ladder. These steps
consist of a surprisingly simple pairing of four nucleic acid bases: guanine
(G), adenine (A), thymine (T), and cytosine (C). These bases pair up to one
another like lock and key with guanine pairing with cytosine and adenine pairing
simple, predictable pairing allows life to happen. It provides a way to encode
the genetic instructions needed to build and maintain cells. Under the influence
of various enzymes, the DNA molecules unfasten and come apart like zippers,
which provide the pattern for creating new strands of DNA.
sort of base pairing is universal in all known life. If it has DNA, then it uses
G-C and A-T pairs. The question is, is this pairing universal because of all
life on Earth having a common ancestor, is it because of some fundamental law of
chemistry, or both?
result of years of research going back to the late 1990s, the TSRI team’s
project aimed to find molecules that would pair like those in DNA and would form
stably on the helix backbone of the DNA molecule. They would also need to unzip
like the known bases and transcribe onto the RNA
molecules to create new DNA strands. In addition, they had to be able to survive
the DNA repair mechanisms in the cell that might see the new bases as faulty
strands and remove them.
2008, the team was able to create semi-artificial strands of DNA that would
replicate in a test tube in the presence of the right enzymes and would
transcribe onto RNA, but, according to the team, the
big leap was to get the strands to work in a living cell. They did this by
creating a plasmid, which is a circular strand of DNA, that was a mixture of
natural and artificial DNA elements made of molecules known as d5SICS and dNaM,
and then inserting it into escherichia coli bacteria.
Obviously, the result isn't artificial life, but it is, by
any definition, a novelty. The bacteria carried in their nuclei DNA with
bases not found in any other living organism. The pairs are able to duplicate so
long as the chemical materials are available, and the duplication occurs with
reasonable speed and accuracy, the repair mechanism didn't interfere, and the
growth of the cells was not impaired.
However, the new bacteria are also no Frankenstein’s micro-monsters waiting to
break out of the lab on an unsuspecting world. Since 5SICS and dNaM are not
found in nature, the scientists have to supply them for the DNA strands to form
and they need what are called triphosphate transporter molecules produced by a
species of microalgae to move the molecules into the cells. What all that adds
up to is that the artificial DNA won’t work outside of the laboratory.
we stopped the flow of the unnatural triphosphate building blocks into the
cells, the replacement of d5SICS – dNaM with natural base pairs was very nicely
correlated with the cell replication itself – there
didn’t seem to be other factors excising the unnatural base pairs from the DNA,”
says team member Denis A. Malyshev. "An important thing to note is that these
two breakthroughs also provide control over the system. Our new bases can only
get into the cell if we turn on the ‘base transporter’ protein. Without this
transporter or when new bases are not provided, the cell will revert back to A,
T, G, C, and the d5SICS and dNaM will disappear from the genome."
According to team leader Floyd E. Romesberg, the next goal will be see if the
new bases can be used to create proteins. “In principle, we could encode new
proteins made from new, unnatural amino acids — which would give us greater
power than ever to tailor protein therapeutics and diagnostics and laboratory
reagents to have desired functions. Other applications, such as nanomaterials,
are also possible.”
teams findings were published in Nature.
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