Team Creates Simple Chemical System that Mimics DNA
The work, reported in the June 11, 2009 issue of Science Express, an advance, online publication of the journal Science, might also be a starting point on the way to exotic new materials that repair themselves or transform in response to their environment.
Scientists are both bemused and fascinated by the question of how life could have arisen on Earth. One of the most prominent theories is that, before the emergence of DNA, the earliest forms of life used RNA to transmit their genetic codes. The late Leslie Orgel, a co-author of the new paper, first suggested this idea, known as the "RNA World."
One of the theory's challenges is that RNA is still so complex that many researchers believer something still simpler must have preceded it. "I have been working for years to learn what replicators and genetic systems might have come before the advent of the RNA World," says team leader of the new research Professor Reza Ghadiri, a Scripps Research chemist.
One key focus for Ghadiri's team has been amino acids' potential primordial role. In 1996, the group showed for the first time that amino acid strands, or peptides, can self-replicate under enzyme-free conditions. In the current work, the Ghadiri lab extends this focus by creating another type of information system that might be capable of something akin to Darwinian evolution. "This work is a beginning step toward that goal," says Ghadiri.
Thioester bonds reversibly with the cysteine on the peptides to form thioester peptide nucleic acid (tPNA). This allows the nucleobases to attach and disassemble on their own without enzymes, so that a given peptide strand will hold a shifting array of nucleobases. This process is something like soldiers walking around a field achieving a certain formation then moving into a new formation.
If an unzipped segment of DNA is added as a template to a solution with the tPNA components, the nucelobase soldiers will automatically assume a formation on peptide strands that complements the DNA according to standard Watson-Crick pairing of adenine with thymine and cytosine with guanine.
The complementary tPNA and DNA strands bond, but these pairings can then be unzipped by adding to the mix complementary DNA strands, which outcompete the tPNA for space on the initial templates. The DNA-DNA pairings remain stable, causing the tPNA components to resume their unstable shuffling until a new DNA template is added and the process begins again.
The Ghadiri team was also able to show that a strand of tPNA can act as a template, causing complementary tPNA formation and strand pairing, though they have not yet achieved self-replication for tPNA, an ultimate goal.
Beyond origins of life questions, Ghadiri says the work also offers some distant but intriguing possibilities, especially considering that there are almost endless possibilities for creating systems similar to tPNA using differing chemical constituents. Such systems could lead to the formation of new enzymes or other chemicals capable of catalyzing reactions with biomedical or other uses. "The capacity to have nucleic acid-like folded structures with protein features will surely in my mind give us new functionalities," he says, though it is impossible to say yet what those new functionalities might be.
Ghadiri also imagines some science fiction-worthy options for tPNA-related materials such as plastics that can repair themselves when fractured. Another possibility, tied to the way that tPNA rearranges when exposed to differing templates, would be to create materials that can remodel themselves by similarly responding to changes in their environment.
"You can in principle do many things, and we're enthusiastic about the prospects," says Ghadiri. "This is just the beginning."
In addition to Orgel and Ghadiri, authors on the paper, entitled "Self-Assembling Sequence-Adaptive Peptide Nucleic Acids," are Yasuvuki Ura, John Beierle, and Luke Leman, all from The Scripps Research Institute.
This work was supported in part by the Skaggs Institute for Chemical Biology, NASA Earth and Space Science Fellowship Program, and the NASA Science Mission Directorate's Planetary Science Division. The paper is dedicated to the memory of Leslie E. Orgel.