Scientists Engineer Semi-Synthetic Organism with 'Alien' DNA

First Posted: May 08, 2014 07:20 AM EDT

Scientists have managed to create the first living organism with added DNA. The researchers engineered a bacterium whose genetic material includes an added pair of DNA "letters," or bases, not found in nature.

The researchers have been working on this particular project since the late 1990s. They've searched for pairs of molecules that could serve as new, functional DNA bases.

"Life on Earth in all its diversity is encoded by only two pairs of DNA bases, A-T and C-G, and what we've made is an organism that stably contains those two plus a third, unnatural pair of bases," said Floyd E. Romesberg, one of the researchers, in a news release. "This shows that other solutions to storing information are possible and, of course, takes us closer to an expanded-DNA biology that will have many exciting applications-from new medicines to new kinds of nanotechnology."

Actually discovering functional new pairs of DNA bases wasn't easy, though. The researchers had to find bases that would line up stably alongside natural bases in a zipper-like stretch of DNA. These synthetic bases would also have to unzip and re-zip smoothly during DNA replication. In 2008, though, the scientists made a breakthrough; they found sets of nucleoside molecules that can hook up across a double-strand of DNA almost as snugly as natural base pairs.

In this latest study, the researchers have taken another step. They synthesized a stretch of circular DNA known as a plasmid and then inserted it into cells of the bacterium, E. coli. This plasmid contained natural DNA along with the best performing unnatural base pair: d5SSICS and dNaM. It turns out that this unnatural DNA did not hamper the growth of the E. coli cells.

"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," said Denis Malyshev, one of the researchers, in a news 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."

The findings reveal that this synthetic DNA is possible, which could pave the way for future research.

The findings are published in the journal Nature.

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