A Ludwig-Maximilians-Universitaet (LMU) in Munich team has shown that slight
alterations in transfer-RNA molecules (tRNAs) allow them to self-assemble into
a functional unit that can replicate information exponentially. tRNAs are key
elements in the evolution of early life-forms.
Life as we know it is based on a complex network of interactions, which take
place at microscopic scales in biological cells, and involve thousands of
distinct molecular species. In our bodies, one fundamental process is
repeated countless times every day. In an operation known as replication,
proteins duplicate the genetic information encoded in the DNA molecules
stored in the cell nucleus -- before distributing them equally to the two
daughter cells during cell division. The information is then selectively
copied ('transcribed') into what are called messenger RNA molecules (mRNAs),
which direct the synthesis of the many different proteins required by the
cell type concerned. A second type of RNA -- transfer RNA (tRNA) -- plays a
central role in the 'translation' of mRNAs into proteins. Transfer RNAs act
as intermediaries between mRNAs and proteins: they ensure that the
amino-acid subunits of which each particular protein consists are put
together in the sequence specified by the corresponding mRNA.
How could such a complex interplay between DNA replication and the
translation of mRNAs into proteins have arisen when living systems first
evolved on the early Earth? We have here a classical example of the
chicken-and-the-egg problem: Proteins are required for transcription of the
genetic information, but their synthesis itself depends on transcription.
LMU physicists led by Professor Dieter Braun have now demonstrated how this
conundrum could have been resolved. They have shown that minor modifications
in the structures of modern tRNA molecules permit them to autonomously
interact to form a kind of replication module, which is capable of
exponentially replicating information. This finding implies that tRNAs --
the key intermediaries between transcription and translation in modern cells
-- could also have been the crucial link between replication and translation
in the earliest living systems. It could therefore provide a neat solution
to the question of which came first -- genetic information or proteins?
Strikingly, in terms of their sequences and overall structure, tRNAs are
highly conserved in all three domains of life, i.e. the unicellular Archaea
and Bacteria (which lack a cell nucleus) and the Eukaryota (organisms whose
cells contain a true nucleus). This fact in itself suggests that tRNAs are
among the most ancient molecules in the biosphere.
Like the later steps in the evolution of life, the evolution of replication
and translation -- and the complex relationship between them -- was not the
result of a sudden single step. It is better understood as the culmination
of an evolutionary journey. "Fundamental phenomena such as self-replication,
autocatalysis, self-organization and compartmentalization are likely to have
played important roles in these developments," says Dieter Braun. "And on a
more general note, such physical and chemical processes are wholly dependent
on the availability of environments that provide non-equilibrium
conditions."
In their experiments, Braun and his colleagues used a set of reciprocally
complementary DNA strands modeled on the characteristic form of modern
tRNAs. Each was made up of two 'hairpins' (so called because each strand
could partially pair with itself and form an elongated loop structure),
separated by an informational sequence in the middle. Eight such strands can
interact via complementary base-pairing to form a complex. Depending on the
pairing patterns dictated by the central informational regions, this complex
was able to encode a 4-digit binary code.
Each experiment began with a template -- an informational structure made up
of two types of the central informational sequences that define a binary
sequence. This sequence dictated the form of the complementary molecule with
which it can interact in the pool of available strands. The researchers went
on to demonstrate that the templated binary structure can be repeatedly
copied, i.e. amplified, by applying a repeating sequence of temperature
fluctuations between warm and cold. "It is therefore conceivable that such a
replication mechanism could have taken place on a hydrothermal microsystem
on the early Earth," says Braun. In particular, aqueous solutions trapped in
porous rocks on the seafloor would have provided a favorable environment for
such reaction cycles, since natural temperature oscillations, generated by
convection currents, are known to occur in such settings.
During the copying process, complementary strands (drawn from the pool of
molecules) pair up with the informational segment of the template strands.
In the course of time, the adjacent hairpins of these strands also pair up
to form a stable backbone, and temperature oscillations continue to drive
the amplification process. If the temperature is increased for a brief
period, the template strands are separated from the newly formed replicate,
and both can then serve as template strands in the next round of
replication.
The team was able to show that the system is capable of exponential
replication. This is an important finding, as it shows that the replication
mechanism is particularly resistant to collapse owing to the accumulation of
errors. The fact that the structure of the replicator complex itself
resembles that of modern tRNAs suggests that early forms of tRNA could have
participated in molecular replication processes, before tRNA molecules
assumed their modern role in the translation of messenger RNA sequences into
proteins. "This link between replication and translation in an early
evolutionary scenario could provide a solution to the chicken-and-the-egg
problem," says Alexandra Kühnlein. It could also account for the
characteristic form of proto-tRNAs, and elucidate the role of tRNAs before
they were co-opted for use in translation.
Laboratory research on the origin of life and the emergence of Darwinian
evolution at the level of chemical polymers also has implications for the
future of biotechnology. "Our investigations of early forms of molecular
replication and our discovery of a link between replication and translation
brings us a step closer to the reconstruction of the origin of life," Braun
concludes.
Reference:
Alexandra Kühnlein, Simon A Lanzmich, Dieter Braun. tRNA sequences can
assemble into a replicator. eLife, 2021; 10 DOI:
10.7554/eLife.63431
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