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Venter Institute Scientists Create First Synthetic Bacterial Genome

A team of 17 researchers at the J. Craig Venter Institute (JCVI) has created the largest man-made DNA structure by synthesizing and assembling the 582,970 base pair genome of a bacterium, Mycoplasma genitalium JCVI-1.0.

This work, published online today in the journal Science by Dan Gibson, Ph.D., et al, is the second of three key steps toward the team’s goal of creating a fully synthetic organism. (Earlier post.) In the next step, which is ongoing at the JCVI, the team will attempt to create a living bacterial cell based entirely on the synthetically made genome.

The team achieved this technical feat by chemically making DNA fragments in the lab and developing new methods for the assembly and reproduction of the DNA segments. After several years of work perfecting chemical assembly, the team found they could use homologous recombination (a process that cells use to repair damage to their chromosomes) in the yeast Saccharomyces cerevisiae to rapidly build the entire bacterial chromosome from large subassemblies.

The building blocks of DNA—adenine (A), guanine (G), cytosine (C) and thiamine (T)—are not easy chemicals to artificially synthesize into chromosomes. As the strands of DNA get longer they get increasingly brittle, making them more difficult to work with. Prior to today’s publication the largest synthesized DNA contained only 32,000 base pairs.

The process to synthesize and assemble the synthetic version of the M. genitalium chromosome began first by resequencing the native M. genitalium genome to ensure that the team was starting with an error-free sequence. After obtaining this correct version of the native genome, the team specially designed fragments of chemically synthesized DNA to build 101 “cassettes” of 5,000 to 7,000 base pairs of genetic code.

As a measure to differentiate the synthetic genome versus the native genome, the team created “watermarks” in the synthetic genome. These are short inserted or substituted sequences that encode information not typically found in nature. Other changes the team made to the synthetic genome included disrupting a gene to block infectivity. To obtain the cassettes the JCVI team worked primarily with the DNA synthesis company Blue Heron Technology, as well as DNA 2.0 and GENEART.

From here, the team devised a five-stage assembly process where the cassettes were joined together in subassemblies to make larger and larger pieces that would eventually be combined to build the whole synthetic M. genitalium genome. In the first step, sets of four cassettes were joined to create 25 subassemblies, each about 24,000 base pairs (24kb). These 24kb fragments were cloned into the bacterium Escherichia coli to produce sufficient DNA for the next steps, and for DNA sequence validation.

The next step involved combining three 24kb fragments together to create 8 assembled blocks, each about 72,000 base pairs. These 1/8th fragments of the whole genome were again cloned into E. coli for DNA production and DNA sequencing. Step three involved combining two 1/8th fragments together to produce large fragments approximately 144,000 base pairs or 1/4th of the whole genome.

At this stage the team could not obtain half genome clones in E. coli, so the team experimented with yeast and found that it tolerated the large foreign DNA molecules well, and that they were able to assemble the fragments together by homologous recombination. This process was used to assemble the last cassettes, from 1/4 genome fragments to the final genome of more than 580,000 base pairs. The final chromosome was again sequenced in order to validate the complete accurate chemical structure.

The synthetic M. genitalium has a molecular weight of 360,110 kilodaltons (kDa). Printed in 10 point font, the letters of the M. genitalium JCVI-1.0 genome span 147 pages.

The research to create the synthetic M. genitalium JCVI-1.0 was funded by Synthetic Genomics, Inc. Also founded by Venter, Synthetic Genomics is focused on developing genomic-driven strategies to address global energy and environmental challenges.

In 2007, the company entered a collaboration with BP to develop biological conversion processes for subsurface hydrocarbons that could lead to cleaner energy production and improved recovery rates. As part of that deal, BP invested in the company. (Earlier post.)




Venter is the guy that wanted to patent the human genome a while back. It seems like he will do anything for money and it does not matter who he hurts in the process.


Well, he does like to put his name on stuff. However, I think his heart is in the right place on this. The technology does look like something with abuse potential. There was a popular myth in some segments of the Black community about 10 or so years ago that the HIV virus was engineered by "The Government" in order to kill Black people. Of course that was utter nonsense, but if you fast forward Venter's technology a decade or two, such a thing as creating a virus to kill, say, Northern Europeans, or Asians, or Blacks, or whatever might be possible. Maybe we oughta start being nicer to each other. On the other hand, we might get some cheap gas out of it so GM can do something about the shocking 20% fall in Hummer sales.

Rafael Seidl

Any technology can be abused for military or other nefarious purposes. GM is no different in that regard from the internal combustion engine. The trick is to keep lawmakers and society sufficiently abreast of what is and what isn't possible so they can create appropriate oversight mechanism for this emerging industry. A knee-jerk Luddite response underestimates the potential benefits just as much as a laissez-faire approach ignores the risks.

In this particular case, Mr. Venter's team has succeeded in artificially re-creating the complete DNA of one extremely simple bacterium, with a few deliberate modifications to make it both easily identifiable and harmless. However, they have not (yet) successfully inserted this DNA into a living cell. They have also not (yet) tackled a complex organism, nor have they (yet) created any novel metabolic pathways.

That said, this team and its competitors are forging ahead at high speed. It is only be a matter of time before someone somewhere reaches these additional milestones en route to the ill-defined destination. An informed, rational public discussion of the risks, benefits and legal ramifications of complete-DNA GM is urgently needed. Unfortunately, it is likely to be overshadowed by religious zealots who may not even know very much about the science.

Bob Bastard

Yes, gotta love those religious wacky religious zealots. They put the fun in fundamentalism. No doubt they will be able to delay rational debate and progress on GM just as they have with stem cell research, but in the end progress will march forward with or without their consent.


"In 2007, the company entered a collaboration with BP to develop biological conversion processes for subsurface hydrocarbons..."

One might wonder if applying this level of DNA modification to the extraction of oil is a prudent place to begin. I would imagine there are far more benevolent applications for GM than to assist in a process already determined to undermine the ecological health of the planet.


Maybe if they succeed in making these microscopic hydrocarbon munchers they will be able to engineer plastic-eating bugs to decompose non-biodegradable plastic.

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