Semi-Synthetic Organism Uses New DNA Bases

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Life, on the most basic level, is incredibly simple in theory yet vastly complex in practice. DNA is made out of only four nucleic acids: adenine which pairs with thymine, and cytosine which pairs with guanine. For simplicity’s sake, these molecules are typically referred to by just their first letter. A set of three ‘letters’ is known as a codon, which is how DNA is read. There are 64 possible codons that code for one of 20 standard amino acids (though three are used for punctuation purposes) for eukaryotes. The order in which the amino acids are put in the chain will determine the shape, structure, and function of all the different proteins created.

If all of that diversity can stem from only 4 nucleic acids, what would happen if new ‘letters’ were introduced to the genetic alphabet? Recent research led by Floyd Romesberg of The Scripps Research Institute leads us one step closer as his team has created a plasmid with a novel pair of nucleic acids known as d5SICS and dNaM in the sequence and introduced it into E. coli bacteria. Though this has been shown possible in a test tube, this is the first time it has been accomplished in an organism. The details of the research have been described in Nature.

Before anyone gets worried that this new DNA data is going to take over the world or some such nonsense, don’t get too ahead of yourself. Since these molecules aren’t found in natural cells, the ingredients to make them aren’t readily available in cells either. The researchers were able to make this breakthrough by utilizing a triphosphate transporter found in microalgae that was capable of dealing with these new additions.

"When we stopped the flow of the unnatural triphosphate building blocks into the cells, the replacement of d5SICS-dNaM with natural base pairs was very nicely correlated with the cell replication itself—there didn't seem to be other factors excising the unnatural base pairs from the DNA," lead author Denis Malyshev said in a press release. "An important thing to note is that these two breakthroughs also provide control over the system. Our new bases can only get into the cell if we turn on the 'base transporter' protein. Without this transporter or when new bases are not provided, the cell will revert back to A, T, G, C, and the d5SICS and dNaM will disappear from the genome."

While these new molecules work well during DNA replication, the next steps in the research will be to manipulate RNA so they can be integrated into the synthesis of new unnatural proteins. This could be used for information storage as well as a new family of nanomaterials.

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