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Our own genetic material is DNA. Its backbone is made of sugar and
phosphate building blocks. Like a strand of pearls, the four “letters”
of the genetic code are arranged along this backbone. Two
complementary strands of DNA form a double helix because the purine
bases adenine (A) and guanine (G) form specific pairs with the
pyrimidine bases thymine (T) and cytosine (C), attaching to each other
through two or three docking sites. This type of structure could also
be the basis for the first genetic material. However, it is doubtful
that its backbone consisted of sugar and phosphate; it may have
consisted of peptide-like building blocks. Amino acids, from which
peptides are made, were already present in the “primordial soup”.
However, the bases may also have looked different in their primitive
form.
To find the right track in searching for the origins of life, the team
is trying to put together groups of potential building blocks from
which primitive molecular information transmitters could have been
made. The researchers have taken a pragmatic approach to their
experiments. Compounds that they test do not need to fulfill specific
chemical criteria; instead, they must pass their “genetic information”
on to subsequent generations just as simply as the genetic molecules
we know today - and their formation must have been possible under
prebiotic conditions. Experiments with molecules related to the usual
pyrimidine bases (pyrimidine is a six-membered aromatic ring
containing four carbon and two nitrogen atoms), among others, seemed a
good place to start. The team thus tried compounds with a triazine
core (a six-membered aromatic ring made of three carbon and three
nitrogen atoms) or aminopyridine core (which has an additional
nitrogen- and hydrogen-containing side group). Imitating the
structures of the normal bases, the researchers equipped these with
different arrangements of nitrogen- and hydrogen- and/or
oxygen-containing side groups.
Unlike the usual bases, these components can easily be attached to
many different types of backbone, for example, a backbone made of
dipeptides or other peptide-like molecules. In this way, the
researchers did indeed obtain molecules that could form specific base
pairs not only with each other, but also with complementary RNA and
DNA strands. Interestingly, only one sufficiently strong pair was
formed within both the triazine and aminopyridine families; however,
for a four-letter system analogous to the ACGT code, two such strongly
binding pairs are necessary. “Our results indicate that the structure
of the bases, rather than the structure of the backbone, was the
critical factor in the development of our modern genetic material,”
says Krishnamurthy. Many chain molecules are able to adopt a suitable
spatial structure, but only a few bases can enter into the necessary
specific pairing. In this, our alternative bases are clearly inferior
to the usual Watson–Crick bases. “Based on our observations, we are
beginning to understand why the natural bases are optimal with regard
to the function they perform.”
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