Weird Engineered Organism Has 6-Letter DNA

The first report of a bacterium whose genome contains man-made DNA building blocks opens the door for tailor-made organisms that could be used to produce new drugs and other products.

All living creatures have a DNA "alphabet" of just four letters, which encode instructions for the proteins that perform most of the key jobs inside cells. But expanding that alphabet to include artificial letters could give organisms the ability to produce new proteins never seen before in nature.

The man-made DNA could be used for everything from the manufacture of new drugs and vaccines to forensics, researchers say.

"What we have done is successfully store increased information in the DNA of a living cell," study leader Floyd Romesberg, a chemical biologist at The Scripps Research Institute in La Jolla, Calif., told Live Science. Yet many steps remain before Romesberg and his colleagues can get cells to produce artificial proteins. [Biomimicry: 7 Clever Technologies Inspired by Nature]

DNA alphabet The field of synthetic biology involves tinkering with DNA to create organisms capable of novel functions in medicine, energy and other areas.

The DNA alphabet consists of four letters, or bases: adenine, thymine, guanine and cytosine (A, T, G and C). Adenine pairs with thymine, and guanine pairs with cytosine. RNA is a genetic material similar to DNA, except it has a different chemical backbone and replaces the base thymine with uracil (U).

Living things translate DNA into proteins through a series of steps. First, enzymes "transcribe" the DNA into RNA. Then, structures called ribosomes translate the DNA into proteins, which are made up of strands of molecules called amino acids.

Ultimately, the researchers aim to create organisms that can produce artificial proteins. But first, they need to show that the DNA containing the man-made letters can be transcribed into RNA, and that this RNA can be translated into proteins.

In the study, Romesberg and his team created an new pair of DNA letters not found in nature and inserted the pair into cells of Escherichia coli bacteria. Getting the DNA into the cells is not easy, but the researchers were able to do it by way of a transporter, a protein that moves materials across cell membranes.

Inside the cells, the man-made DNA got spliced into a plasmid, a circular piece of DNA found in bacteria. The plasmids replicated, without rejecting the foreign DNA or affecting the cells' growth, the researchers reported.

Now that the scientists have demonstrated an organism can incorporate artificial DNA letters into its genome, the next step will be showing it can convert the DNA into new proteins, which could be used to produce better drugs.

Custom-made drugs Proteins have become an important new type of drug, because cells can do the work of making them and because molecular biology techniques can be used to help proteins "evolve" to have desired properties, Romesberg said. But proteins are limited to only 20 building blocks, known as amino acids.

"Compare this to a medicinal chemist, who explores a much greater diversity of structures in the small-molecule drugs they synthesize," Romesberg said. "We hope to be able to combine the best of both small-molecule and protein drugs."

The research paves the way for "designer" organisms with custom-made genomes that are capable of performing useful tasks, like making drugs. Already, researchers have created the first "synthetic organisms" - artificial bacteria and yeast - which have man-made DNA sequences in their genomes.

The researchers are now working on expanding the DNA alphabet of yeast cells, and eventually hope to do the same for mammalian cells, which have properties that make them better at producing protein drugs.

Expanding the genetic alphabet of an entire multicellular organism such as a human wouldn't be possible with the current technique, however, because the artificial letters must be directly inserted into each cell, Romesberg said.

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Researchers added new letters to the DNA alphabet of an organism, shown here as printing blocks.

New technologies could make it possible to bring extinct species back to life, concludes a paper published on April 4 in the journal Science. These advances include back-breeding (assembling or reassembling an extinct species' genes), cloning and genetic engineering.

Woolly Mammoth

A leading candidate for de-extinction is the woolly mammoth. Russian scientist Semyon Grigoriev, of the Sakha Republic's mammoth museum, plans to replace the nuclei of an elephant egg with nuclei extracted from woolly mammoth bone marrow. The elephant would theoretically become a surrogate mother to a baby mammoth.

Tasmanian Tiger

Tasmanian tigers died out in 1936, in part because they had little genetic diversity which translates to "bad news for a species," said Katherine Belov, professor of comparative genomics at the University of Sydney. "Species are less able to adapt to change." Even if Tasmanian tigers -- or other animals -- are resurrected, it will take some time to build up diversity again.

Passenger Pigeon


Experts believe billions of these birds populated the Americas when Europeans arrived. Loss of habitat and commercial exploitation of the birds for their meat are thought to have killed them all off.

Efforts are now underway to revive the species by extracting DNA fragments from preserved specimens, and later, using band-tailed pigeons as surrogate parents.

Pyrenean Ibex


The Pyrenean ibex, a horned mammal once common in Europe, was one of the first subspecies targeted for de-extinction. Scientists began the attempts in late 1990s, when the last female Pyrenean ibex was still alive. Even if researchers could successfully clone that individual, there would be no males for her to breed with. Instead, genetic engineering might be required.

Saber-toothed Cat


Since saber-toothed cat bodies are sometimes found frozen, it might be possible to extract preserved DNA and clone the animal. About 5 years ago, scientists did just that with a mouse that was dead and frozen for 16 years. Woolly mammoth remains are also sometimes found in a well-preserved, frozen state.

Dodo Bird


The dodo, a flightless bird, proved to be a tasty meal for humans and other predators. In 2007, scientists found a remarkably well-preserved dodo in a cave. Dodo DNA could be used to resurrect this avian species.


Ground Sloth


Ground sloths, relatively slow, lumbering animals, were easy targets for prehistoric big-game hunters. Scientists have found remains that still bear soft tissue. As with woolly mammoths, there's a chance extracted DNA could be used to back-breed or clone the large sloths.

Irish Elk


The Irish elk has been extinct for 11,000 years. Like the woolly mammoth, it inhabited colder regions. As a result, bodies are sometimes found frozen and in relatively good condition, making them candidates for DNA extraction.

Neanderthal

Earlier this year, Harvard geneticist George Church -- with tongue in cheek -- said that he was seeing an "adventurous female human" to be a surrogate mother to a cloned Neanderthal. While Church was really just theorizing about what it would take to bring a Neanderthal back to life, the possibility could be a reality, should any scientist undertake such a controversial project.

Dinosaur

Paleontologist Jack Horner is leading a project to create a dinosaur out of a chicken -- a "dinochicken." He told Discovery News that birds "are dinosaurs, so technically we're making a dinosaur out of a dinosaur." He and his colleagues have been genetically engineering chickens to reactivate ancestral traits, such as long tails, which are more associated with non-avian dinosaurs.