DNA tile ribbons (shown here in an atomic force microscopy image) can store information in their arrangement of tiles—12.5 nm by 4 nm by 2 nm self-assembled DNA structures. This information can be propagated during ribbon growth, and replicated in a cycle of ribbon growth and breakage, or scission. Image: Rebecca Schulman
When scientists think about the replication of
information in chemistry, they usually have in mind something akin to what
happens in living organisms when DNA gets copied: a double-stranded molecule
that contains sequence information makes two new copies of the molecule. But
researchers at the California Institute of Technology (Caltech) have now shown
that a different mechanism can also be used to copy sequence information.
In this alternate version, tiny DNA tile crystals
consisting of many copies of a piece of information are first grown, then
broken into a few pieces by mechanically induced scission, or force. The new
crystal bits contain all the information needed to keep copying the sequence.
Each piece then begins to replicate its information and grow until broken apart
again—without the help of enzymes, an essential ingredient in biological
sequence replication. In some ways, the new system is reminiscent of Goethe’s
poem, The Sorcerer’s Apprentice,
in which the apprentice smashes a magic mop with an axe, producing many exact
replicas of the sweeper, all programmed to do the same job.
“The genome-copying mechanism used by cells requires
tight control between the separation of DNA strands and the copying
process,” explains study lead author Rebecca Schulman, an assistant
professor at Johns Hopkins University who was a graduate student at Caltech
when the research began.
“But no such coordination is required in the system
we designed, which makes it simpler in many ways,” she says. “This
suggests that there may be other mechanisms of copying information that follow
this method using chemistry that could be simpler than the process cells use.
What we showed in the paper was a capacity to take a given chemical message—a
sequence of 1s and 0s—and make more copies of that message through a new, designed
The findings were reported in the Proceedings of the National Academy of Sciences
The idea that crystals can self-replicate was first
presented by organic chemist and molecular biologist Graham Cairns-Smith in
1965. He proposed, as well, that such crystals might have been the first
chemical self-replicators capable of Darwinian evolution. His theory was
controversial at the time, and his ideas have never gained widespread support.
But according to Erik Winfree, professor of computer science, computation and
neural systems, and bioengineering at Caltech and senior author on the PNAS paper, this new research shows
that Cairns-Smith’s hypothesis on the origin of life is demonstrably more
plausible than previously thought.
“Overall, we found that his principles and
mechanisms are sound, and although we didn’t experimentally demonstrate his
theory all the way, self-replication via crystal growth and scission should be
sufficient for Darwinian evolution,” he says. “This is because DNA
tile crystals can be programmed to process information during growth, allowing
them to adapt to their environment. Our findings could even form the basis of
novel molecular technologies for making complex self-replicating nanoscale
Their new research found that it is possible to design a
mechanism for copying chemical information very accurately without relying on
biological enzymes to assemble and separate sequence copies. Instead, the
researchers relied only on simple kinds of attachments—molecular binding and
unbinding reactions that they designed—and mechanical forces.
Having shown that information can be made to chemically
self-replicate, says Schulman, the question becomes, what kinds of messages can
be copied in this way?
“Our theoretical work suggests that not just linear
sequences but also patterns in two dimensions, similar to wallpaper patterns
that repeat every so often, could also be replicated,” she says.
The crystals used in the study simply copied information
verbatim from layer to layer as they grew, which in itself is insufficient to
kick-start a Darwinian evolutionary process. But crystal growth that produces complex
patterns resulting in 2D or 3D structures would, in this context, correspond to
a rudimentary “genotype-phenotype” relationship, thereby enriching
the Darwinian evolutionary process by introducing complex forms that would be
subject to selective pressures, Winfree says.
“Our findings show that
there is a bewildering variety of imaginable ways that chemical systems could
self-replicate and evolve,” he says. “This really puts into question
whether or not the way biology does things now is the only possible way that
life could be organized on a molecular level.”