Science

Life, but not as we know it: Scientists engineer first semisynthetic organism with three-base-pair DNA

Life, but not as we know it: S...
Scientists claim to have created the first stable, replicating semisynthetic organism to contain an extra pair of artificial bases in its genetic code
Scientists claim to have created the first stable, replicating semisynthetic organism to contain an extra pair of artificial bases in its genetic code
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Professor Floyd Romesberg (right) and Graduate Student Yorke Zhang led the new study at The Scripps Research Institute
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Professor Floyd Romesberg (right) and Graduate Student Yorke Zhang led the new study at The Scripps Research Institute
Scientists claim to have created the first stable, replicating semisynthetic organism to contain an extra pair of artificial bases in its genetic code
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Scientists claim to have created the first stable, replicating semisynthetic organism to contain an extra pair of artificial bases in its genetic code

Researchers at The Scripps Research Institute (TSRI) claim to have created the first stable semisynthetic organism with extra bases added to its genetic code. The single-celled organism is also able to continually replicate the synthetic base pair as it divides, which could mean that future synthetic organisms may be able to carry extra genetic information in their DNA sequences indefinitely.

The cells of all organisms contain genetic information in their DNA as a two-base-pair sequence made up of four molecules – A, T, C, G (Adenine, Cytosine, Thymine, and Guanine). Each of these is known as a nucleotide (consisting of a a nitrogenous base, a phosphate molecule, and a sugar molecule) and are specifically and exclusively paired, so that only A is coupled to T and C is coupled with G. These nucleotides are connected in a chain by the covalent (electron-coupled) bonds between the sugar of one nucleotide and the phosphate of the next, which creates an alternating sugar-phosphate "backbone."

The team from TSRI have added two synthetic bases that they call "X" and "Y" into the genetic code of a E.coli carrier organism – a single-cell bacteria – and then chemically tweaked it to live, replicate, and survive with the extra DNA molecules intact.

"We've made this semisynthetic organism more life-like," said Professor Floyd Romesberg, senior author of the new study. "We can now get the light of life to stay on. That suggests that all of life's processes can be subject to manipulation."

Professor Floyd Romesberg (right) and Graduate Student Yorke Zhang led the new study at The Scripps Research Institute
Professor Floyd Romesberg (right) and Graduate Student Yorke Zhang led the new study at The Scripps Research Institute

Building on previous work on the development of X and Y in 2014, the team demonstrated at the time that engineered E. coli bacteria could hold the artificial base pair in their genetic code temporarily, but would then lose them when the organism divided.

"Your genome isn't just stable for a day," said Romesberg. "Your genome has to be stable for the scale of your lifetime. If the semisynthetic organism is going to really be an organism, it has to be able to stably maintain that information."

The addition of the X and Y base pair seemed to affect the health and well-being of the bacteria, meaning that it did not flourish, and was seen to be sluggish, and slow. To help remedy this, the team modified and improved the nucleotide transporter that ferried in the materials that allow the new base pair to be replicated.

Following this, the scientists swapped out the original Y molecule for one that was better recognized by the enzymes in DNA molecules that help out during replication, and then used the genome editing tool CRISPR to modify the bacteria's genome so that it could grow and divide normally, while still being able to pass on the X and Y nucleotides.

Working specifically on the CRISPR-Cas9 DNA segment and an enzyme that acted as part of an immune-response system where fragments of an invader genome are sampled for future responses, the team modified the genetic sequence so that it did not see X and Y as foreign bodies. As a result, the TSRI semisynthetic organism was seen to hold onto the X and Y pair in its genome even after replicating more than 60 times which, the researchers claim, means that the bacteria should be able to indefinitely hold on to the base pair.

Though only able to be used in single-cell organisms and there are no practical applications at this stage, future research is planned to work out how to transcribe the new genetic code into RNA molecules and see how they are affected when used by the cells to create proteins from DNA.

The research results were recently published in the journal Proceedings of the National Academy of Sciences.

Source: The Scripps Research Institute

6 comments
Nairda
"was seen to hold onto the X and Y pair in its genome even after replicating more than 60 times which, the researchers claim, means that the bacteria should be able to indefinitely hold on to the base pair" No mention of the measures taken for containment. Semi organic can be son of gray goo scenario and wind carried virus. They can't foresee what in nature it binds to as it is impossible to test for. Especially for something so basic in structure.
Kpar
Sounds like an "X-Files" episode. What sort of random "coding" have these folks introduced into a replicating organism? What might be the results? We know from experience that the GATC works very well- adding additional base pairs may show us what does not work and why.
Still, I hope that they are using appropriate caution in isolating their experiment.
Douglas E Knapp
This scares the heck out of me! I have worked to keep bad bugs and plants out of the USA and read a lot about all the problems you have on islands like Hawaii. Have you ever seen kudzu in the south of the USA? Like a living plague.
On top of this our understanding of DNA is still very young and the chances for mistakes are huge. Then you have human error. All we need is one scientist working with the flue to do something stupid and this new bug is out the door. Or perhaps and earthquake will crack the lab or it will get hit by a meteor or a religious terrorist will think it's a good idea to set it free.
No one will know the consequences of the release of a strange man made DNA. We are so dumb currently that we GMO foods without medical testing and believe it is OK because the firms doing it says so without independent uninfluenced testing. We can't even predict the weather two months out. In the worst case it could destroy all normal life on Earth.
No one can tell me we have safety procedures so that this could never happened. I have lived through way to many failures. Have nuclear power plants poisoning the world. We have global warming that we can't own up to. We can't even control world population of humans. What are the chances we can do this perfectly?
It is important that we learn about DNA but it must be certain that we don't mess it up! I might sound like a doomsayer but I do believe done right this is the right way to go.
Craig Whitley
Most late night SiFi horror movies start out exactly this way.
StWils
Sometime in the seventies a fish farm in Louisiana started importing 3 types of Asian carp & catfish. At the time there was a tremendous fight over intentionally importing foreign species and the obvious concern about proliferation. The farmers won by asserting that the farm was 80 miles from the nearest body of water. Keep in mind this was in Louisiana. At the time few people could see how a flood could permit fish to escape. Again, this is in Louisiana which by definition floods. A lot & regularly. Those catfish are now more than a thousand miles up the Mississippi river system and tributaries and within about 15 miles from the Great Lakes system environment. They have over whelmed native fish and are very aggressive. The only real alternative is another A level predator with expertise at exhausting a population. Us. So, how do we go about combating this bug or bugs, when they escape?
penrose
@ Douglas E Knapp
Since humans are apparently unable to control themselves, we have scant hope of them controlling their planetary impact.
And I am no Luddite. I love European Civilization. In the hands of thoughtful, responsible people with a touch of common sense.
But we have not even been able to devise a method of consistently choosing leaders who meet that criteria.
I'm afraid that the light at the end of this tunnel is a freight train coming toward us.