Breakthrough in Artificial Genetic Code Could Lead to Custom Drugs

By Carl Engelking | May 7, 2014 12:49 pm

e coli culture

Way back in Biology 101, we learned that DNA is encoded through the nucleotide pairings of adenine to thymine and cytosine to guanine. Since the earliest days of life on Earth, these four chemicals — and only these four chemicals — have made up the DNA of every one of the myriad organisms that inhabit this planet. But what if you could expand that alphabet?

As it turns out, you can. In a paper published today in Nature, scientists report that they’ve successfully introduced an entirely new base pair into the genetic structure of the bacterium E. coli. That makes the bacterium the first semi-synthetic organism carrying an expanded genetic alphabet.

And just as one can create new words with new letters in the alphabet, a synthetic base pair opens up possibilities for custom-built proteins as novel drugs, vaccines and antibiotics.

Creating the Base Pair

In 2012, Floyd Romesberg and colleagues reported that synthetic base pairs could be successfully replicated as part of purified DNA in the lab. Translating this result into a cell was the crucial next step, but its success was far from guaranteed.

In the present study, the team engineered a special E. coli strain which had the new synthetic base pairs spliced into its DNA, as well as a transporter protein that pumped the new molecules into the cell.

When they placed the bacteria into a dish full of synthetic nucleotides, the cells snatched up the molecules as they replicated — fully incorporating the synthetic material into their offsprings’ genetic structure. When the synthetic molecules were removed from the environment, the natural processes of the cell eliminated the synthetic molecules from its DNA and the E. coli returned to its natural state.

Synthorx-HowItWorks

Plenty of Questions

Building a semi-synthetic organism with an expanded genetic alphabet allows researchers to include more information in its DNA than is possible in natural systems. For example, natural DNA yields 20 amino acids for the creation of proteins. In contrast, the introduction of a single synthetic base pair expands the selection of possible amino acids to 172. That, in turn, expands the possibilities of proteins we can assemble out of those amino acids, opening the door to proteins never before seen in the history of life on Earth. Modified E. coli — already the workhorses of synthetic biology — could be miniature factories for custom vaccines, antibiotics and drugs.

But could we create an entirely new organism with unnatural DNA? At the moment, no, says Romesberg. “That’s utterly impossible. That’s just not going to happen. There are too many things that recognize DNA and that manipulate it in a cell,” Romesberg said in a Nature podcast. “It’s too integrated into every facet of a cell’s life.”

 

Synthorx-ExpandingAlphabet

Photo credit: motorolka/Shutterstock

Infographics (2): Synthorx

CATEGORIZED UNDER: Living World, top posts
MORE ABOUT: genetics
  • SixSixSix

    The obvious question is why doesn’t this happen naturally? Why does life confine itself to four base pairs? What is the disadvantage over the evolutionary time scale, or reason that it would be unlikely to happen spontaneously?

    This is not to question the merit of manipulating base pairs artificially one way or the other, but why did three or four billion years of evolution shy away from it?

    • Bradley Proffit

      The amount of changes required to make use of an increase in base pairs goes up exponentially. For example, with just two pairs, the number of two-pair permutations is just four, so the machinery needed to handle that system would be extremely easy to evolve, but those organisms would be at a severe disadvantage because the number and speed of adaptations they could possibly make is so limited. Up to three and it’s six permutations for two pairs. As little adaptations allowed for longer codons (groups of base pairs) and more base pairs, the selective pressure seems to have been that when multiple codons mean the same amino acid, the odds of a deleterious mutation go down, and the greatest utility per unit cost for reading DNA was three base pairs at a time, so any individual with more than just the four bases would lose the benefits of that protection from mutation, while needing to quickly evolve a huge amount of new molecular machinery to correctly handle it, at a resource cost for making those new amino acids, and would probably not benefit much from the increase. That’s how it looks to me, at least!

    • eirikr1

      When researchers were attempting to discover the number of base pairs, it was always presumed it would be four.
      At least four would be required for the amount of amino acids known to exist, and it was thought that nature loved simplicity, not multiplying by 12.5 when it’s easier (and only necessary) to multiply by 4.

      God does not play dice with the Universe.” – Einstein
      (when explaining how do we know that parallel lines *stay* that way for infinity?)

  • Greg Abbott

    Interesting, I wonder if they attempted to infect something with the 6 pair version?

    • ConcernedCitizen31

      Once out of the petri dish, the E.Coli cells with the synthetic bases would just die off and the normal 3bp versions would survive, because there are no X-Y amino acids available in the host organism.

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