After almost 15 years of work and $40 million, a team of scientists at the J. Craig Venter Institute says they have succeeded in creating the first living organism with a completely synthetic genome. This advance could be proof that genomes designed in a computer and assembled in a lab can function in a donor cell, eventually reproducing fully functional living creatures, that is, artificial life.
As described today in the journal Science, the study scientists constructed the genome of the bacterium Mycoplasma mycoides from more than 1,000 sections of preassembled units of DNA. Researchers then transplanted the artificially assembled genome into a M. capricolum cell that had been emptied of its own genome. Once the DNA "booted up," the bacteria began to function and reproduce in the same manner as naturally occurring M. mycoides.
"It's a culmination of a series of impressive steps," Ron Weiss, an associate professor of biological engineering at MIT who was not associated with the study, told LiveScience.com. "If you look over the last few years, at what they've been able to produce, it's definitely impressive. Being able to create genomes of this scale? That's impressive."
To boot up, the DNA utilized elements of the M. capricolum recipient cells, according to study team member Carole Lartigue of the Venter Institute. The bacterial cells still contained certain "machinery" that let them carry out the process of expressing a gene, or taking the genetic code and using it to build proteins – called transcription. When the artificial genome entered the cell, the cellular machines that run DNA transcription recognized the DNA, and began doing their job, Lartigue said.
"This cell's lineage is the computer, it's not any other genetic code," said Daniel Gibson, lead author of the Science paper, also of Venter Institute.
To create the genomes, Gibson and his colleagues used yeast to glue together thousands of DNA snippets, each containing 1,080 base pairs, which they ordered from another lab. To assist in assembly, each section of DNA contained 80 base pairs at every end that instructed the yeast where to join the two strands.
Slowly, the DNA strands came together in runs of tens of thousands of base pairs, and then hundreds of thousands, until the yeast produced a complete 1,080,000-base-pair synthetic genome.
The scientists then compared the completed genome with two previously sequenced, natural M. mycoides genomes that served as road maps. The two road maps differed slightly, forcing the Venter scientists to commit to following one or the other, without knowing which genome was more accurate.
Even a tiny inaccuracy could prevent the inert DNA from activating into a live bacterium, making accuracy paramount. At one point, a single base pair mistake set the entire program back three months. But DNA sequencing accuracy has become so advanced that at least finding the mistakes took only days, not the months needed a decade ago during the infancy of genetic engineering.
However, the synthesis process still introduced some mutations into the M. mycoides genome. The researchers deliberately inserted four sequences of DNA that serve as watermarks so they could distinguish between the naturally occurring and synthetic bacteria.
The watermarks contain a code that translates DNA into English letters with punctuation, allowing the scientists to literally write messages with the genes. When translated, the watermarks spell out the names of the 46 researchers who helped with the project, quotations from James Joyce, physicist Richard Feynman and J. Robert Oppenheimer, and a URL that anyone who deciphers the code can e-mail.
Synthetic bacteria have tantalized scientists for years with the promise of bacterial cultures with computer designed genomes producing custom enzymes, fuels and medications cheaply and efficiently.
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