Featured Research

from universities, journals, and other organizations

Semi-synthetic organism: Scientists create first living organism that transmits added letters in DNA 'alphabet'

Date:
May 7, 2014
Source:
Scripps Research Institute
Summary:
Scientists have engineered a bacterium whose genetic material includes an added pair of DNA “letters,” or bases, not found in nature; the bacterium’s cells can replicate the unnatural DNA bases more or less normally, as long as the molecular building blocks are supplied.

Rendering of DNA (stock image).
Credit: © abhijith3747 / Fotolia

Scientists at The Scripps Research Institute (TSRI) have engineered a bacterium whose genetic material includes an added pair of DNA "letters," or bases, not found in nature. The cells of this unique bacterium can replicate the unnatural DNA bases more or less normally, for as long as the molecular building blocks are supplied.

Related Articles


"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 TSRI Associate Professor Floyd E. Romesberg, who led the research team. "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."

The report on the achievement appears May 7, 2014, in an advance online publication of the journal Nature.

Many Challenges

Romesberg and his laboratory have been working since the late 1990s to find pairs of molecules that could serve as new, functional DNA bases -- and, in principle, could code for proteins and organisms that have never existed before.

The task hasn't been a simple one. Any functional new pair of DNA bases would have to bind with an affinity comparable to that of the natural nucleoside base-pairs adenine-thymine and cytosine-guanine. Such new bases also would have to line up stably alongside the natural bases in a zipper-like stretch of DNA. They would be required to unzip and re-zip smoothly when worked on by natural polymerase enzymes during DNA replication and transcription into RNA. And somehow these nucleoside interlopers would have to avoid being attacked and removed by natural DNA-repair mechanisms.

Despite these challenges, by 2008 Romesberg and his colleagues had taken a big step towards this goal; in a study published that year, they identified sets of nucleoside molecules that can hook up across a double-strand of DNA almost as snugly as natural base pairs and showed that DNA containing these unnatural base pairs can replicate in the presence of the right enzymes. In a study that came out the following year, the researchers were able to find enzymes that transcribe this semi-synthetic DNA into RNA.

But this work was conducted in the simplified milieu of a test tube. "These unnatural base pairs have worked beautifully in vitro, but the big challenge has been to get them working in the much more complex environment of a living cell," said Denis A. Malyshev, a member of the Romesberg laboratory who was lead author of the new report.

Microalgae Lead to Breakthrough

In the new study, the team synthesized a stretch of circular DNA known as a plasmid and inserted it into cells of the common bacterium E. coli. The plasmid DNA contained natural T-A and C-G base pairs along with the best-performing unnatural base pair Romesberg's laboratory had discovered, two molecules known as d5SICS and dNaM. The goal was to get the E. coli cells to replicate this semi-synthetic DNA as normally as possible.

The greatest hurdle may be reassuring to those who fear the uncontrolled release of a new life form: the molecular building blocks for d5SICS and dNaM are not naturally in cells. Thus, to get the E. coli to replicate the DNA containing these unnatural bases, the researchers had to supply the molecular building blocks artificially, by adding them to the fluid solution outside the cell. Then, to get the building blocks, known as nucleoside triphosphates, into the cells, they had to find special triphosphate transporter molecules that would do the job.

The researchers eventually were able to find a triphosphate transporter, made by a species of microalgae, that was good enough at importing the unnatural triphosphates. "That was a big breakthrough for us -- an enabling breakthrough," said Malyshev.

Though the completion of the project took another year, no hurdles that large arose again. The team found, somewhat to their surprise, that the semi-synthetic plasmid replicated with reasonable speed and accuracy, did not greatly hamper the growth of the E. coli cells, and showed no sign of losing its unnatural base pairs to DNA repair mechanisms.

"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," Malyshev said. "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 next step will be to demonstrate the in-cell transcription of the new, expanded-alphabet DNA into the RNA that feeds the protein-making machinery of cells. "In principle, we could encode new proteins made from new, unnatural amino acids -- which would give us greater power than ever to tailor protein therapeutics and diagnostics and laboratory reagents to have desired functions," Romesberg said. "Other applications, such as nanomaterials, are also possible."

Other contributors to the paper, "A semi-synthetic organism with an expanded genetic alphabet," were Kirandeep Dhami, Thomas Lavergne and Tingjian Chen of TSRI, and Nan Dai, Jeremy M. Foster and Ivan R. Corrκa Jr. of New England Biolabs, Inc.

The research was funded in part by the U.S. National Institutes of Health (GM 060005).


Story Source:

The above story is based on materials provided by Scripps Research Institute. Note: Materials may be edited for content and length.


Journal Reference:

  1. Denis A. Malyshev, Kirandeep Dhami, Thomas Lavergne, Tingjian Chen, Nan Dai, Jeremy M. Foster, Ivan R. Corrκa, Floyd E. Romesberg. A semi-synthetic organism with an expanded genetic alphabet. Nature, 2014; DOI: 10.1038/nature13314

Cite This Page:

Scripps Research Institute. "Semi-synthetic organism: Scientists create first living organism that transmits added letters in DNA 'alphabet'." ScienceDaily. ScienceDaily, 7 May 2014. <www.sciencedaily.com/releases/2014/05/140507132129.htm>.
Scripps Research Institute. (2014, May 7). Semi-synthetic organism: Scientists create first living organism that transmits added letters in DNA 'alphabet'. ScienceDaily. Retrieved November 20, 2014 from www.sciencedaily.com/releases/2014/05/140507132129.htm
Scripps Research Institute. "Semi-synthetic organism: Scientists create first living organism that transmits added letters in DNA 'alphabet'." ScienceDaily. www.sciencedaily.com/releases/2014/05/140507132129.htm (accessed November 20, 2014).

Share This


More From ScienceDaily



More Plants & Animals News

Thursday, November 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Pygmy Marmoset Getting a Toothbrush Massage Is the Cutest

Pygmy Marmoset Getting a Toothbrush Massage Is the Cutest

Buzz60 (Nov. 19, 2014) — This rescued pygmy marmoset named Ninita is obsessed with her toothbrush. It's cuteness overload, and Sean Dowling (@SeanDowlingTV) has the amazing video. Video provided by Buzz60
Powered by NewsLook.com
Why Are Chocolate Makers So Worried?

Why Are Chocolate Makers So Worried?

Reuters - Business Video Online (Nov. 19, 2014) — Two big chocolate producers are warning the popular treat could run out by 2020 because people are eating it faster than farmers can grow cocoa. Ciara Lee reports Video provided by Reuters
Powered by NewsLook.com
Tiny Hamster Eating Thanksgiving Meal Breaks the Internet

Tiny Hamster Eating Thanksgiving Meal Breaks the Internet

Buzz60 (Nov. 19, 2014) — A tiny hamster and a bunny and rat enjoy a tiny Thanksgiving meal where they stuff themselves to the brim. Sean Dowling (@SeanDowlingTV) has the cute video. Video provided by Buzz60
Powered by NewsLook.com
Giant Panda at Toronto Zoo Loves Somersaulting in the Snow

Giant Panda at Toronto Zoo Loves Somersaulting in the Snow

Buzz60 (Nov. 19, 2014) — A giant panda at the Toronto Zoo named Da Mao is celebrating the northeast snowfall by playing and tumbling in the snow in his outdoor enclosure. Jen Markham has the story. Video provided by Buzz60
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Plants & Animals

Earth & Climate

Fossils & Ruins

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins