Synthetic XNA Polymers: The Next Frontier of Genetics Research?

Jeffrey Serrill, XNA Synthetic Polymers, Capable of Heredity and Evolution
synthetic polymer bases, replacements for 2-deoxyribose

An international collaboration of biochemists has recently presented an exciting new paper in which they suggest some alternatives to the traditional view that deoxyribonucleic acid (DNA) is the only molecule which could possibly play a long-term role as a reservoir of genetic information. Their work, published last week in the April 20th edition of Science, highlights some of the synthetic polymers which they have recently developed; though these molecules retain the normal bases of DNA, altering their sugar-phosphate backbones has yielded an array of molecules which may be potentially capable of storing information.

The genetic blueprints which form the basis for all life on the planet are encoded in several different nucleic acid molecules, primarily DNA and RNA, and the flow of information (normally from DNA to RNA to protein) from these molecular databases has evolved over time into a seamless, highly conserved process. This process is virtually identical in all organisms, potentially as a result of a common evolutionary heritage or ancestor in the distant past; thus, the normal consensus among biologists is that, had an alternate set of polymers evolved which could also conserve genetic data, such an occurrence would have likely been observed at this point. Additionally, the information which is encoded in DNA molecules must be passed on to daughter cells (following replication) while maintaining its fidelity, and also be capable of exhibiting evolution through mutation; without these capabilities, any sort of “alternative” storage system would be relatively useless.

Despite the fact that such genetic storage molecules have not evolved in the natural world, the ability to create synthetic alternatives to DNA is not that far-fetched. In their most basic form, DNA molecules can be thought of as antiparallel helices of matched complementary nucleotides composed of two important parts; the nucleoside bases, which carry the genetic information, and the sugar-phosphate backbone, which gives DNA a double helical shape and helps maintain stability of the molecule. Both of these components are essential to the functional capabilities of DNA, and any research directed at the synthesis of a DNA “alternative” would necessarily have to accomplish both feats. While a number of previous studies have aimed to modify the structures of the nucleoside bases with varied success, a different approach was utilized by the researchers of the recent paper, in which they modified the sugar-phosphate backbones of the information-containing polymers. In this manner, it was hoped that a polymer could be developed which could adequately interact with normal DNA molecules.

"There's a lot of chemisty that seeks to build alternative nucleic acids, and people have been modifying the bases, the sugars and the backbone, but what we were focusing on was the type of nucleic acid or polymers that would retain the ability to communicate with the natural DNA," said Dr Philipp Holliger, one of the collaborators of the study in a recent interview with Science.

The synthetic molecules, referred to collectively as “XNAs” are of several different types, though all appear to act as suitable replacements for DNA through the incorporation of various sugars to replace the normal 2-deoxyribose which links phosphate groups together in the backbone of DNA. Of particular note are these synthetic polymers’ abilities to facilitate the passing of genetic information to the next generation. To demonstrate this, the research team developed a specialized polymerase (enzymes which allow DNA replication to proceed) which was able to take a DNA template, replicate this template into XNA, and then back into DNA. Additionally, after several generations of replication had occurred, the efficiency of this synthesis actually improved, suggesting that some version of short-term molecular evolution was indeed taking place.

"We've been able to show that both heredity - information storage and propagation - and evolution, which are really two hallmarks of life, can be reproduced and implemented in alternative polymers other than DNA and RNA," Dr Holliger further explained.

Though it is perhaps too early to gauge what the potential utilization of such research might be, a final interesting point to note is that these XNA polymers all seem to exhibit a stability which rivals that of both DNA and RNA. With this in mind, it will be very interesting to monitor how the scientific community chooses to utilize these research findings. In the same issue of Science that the research article is presented, Gerald Joyce of the Scripps Research Institute wrote that "the work heralds the era of synthetic genetics, with implications for exobiology (life elsewhere in the Universe), biotechnology, and understanding of life itself".

For more information, see the original research article

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