Mycoplasma Laboratorium - Minimal Genome Project

Minimal Genome Project

The team started with the bacterium M. genitalium, an obligate intracellular parasite whose genome consists of 482 genes comprising 582,970 base pairs, arranged on one circular chromosome (the smallest genome of any known natural organism that can be grown in free culture). They then systematically removed genes to find a minimal set of 382 genes that can sustain life. This effort was also known as the Minimal Genome Project.

The team intends to synthesize chromosome DNA sequences consisting of these 382 genes. Once a version of the minimal 382-gene chromosome has been synthesized, it is intended to be transplanted into a M. genitalium cell to create Mycoplasma laboratorium.

The resulting Mycoplasma laboratorium bacterium is expected to be able to replicate itself with its man-made DNA, making it the most synthetic organism to date, although the molecular machinery and chemical environment that would allow it to replicate would not be synthetic.

In December 2003, the team had reported a fast method of synthesizing a genome from scratch, producing the 5386-base genome of the bacteriophage Phi X 174 in about two weeks. However, the genome of Mycoplasma laboratorium is about 50 times larger. In January 2008, the team reported to have synthesized the complete 582,970 base pair chromosome of M. genitalium, with small modifications so that it won't be infectious and can be distinguished from the wild type. They named this genome Mycoplasma genitalium JCVI-1.0. The team had also demonstrated the process of transplanting a (non-synthetic) genome from one Mycoplasma species to another in June 2007. In May 2010 they showed that they were able to synthesize the 1,078,809 base pair genome of Mycoplasma mycoides from scratch and transplant it into a Mycoplasma capricolum cell; the new genome then took over the cell and the new organism multiplied. The new organism was nicknamed Synthia.

The J. Craig Venter Institute filed patents for the Mycoplasma laboratorium genome (the "minimal bacterial genome") in the U.S. and internationally in 2006. This extension of the domain of biological patents is being challenged by the watchdog organization Action Group on Erosion, Technology and Concentration.

Venter hopes to eventually synthesize bacteria to manufacture hydrogen and biofuels, and also to absorb carbon dioxide and other greenhouse gases. George M. Church, another pioneer in synthetic biology, holds that E. coli is a more efficient organism than M. genitalium and that creating a fully synthetic genome is not necessary and too costly for such tasks; he points out that synthetic genes have already been incorporated into E.coli to perform some of the above tasks. On June 28, 2007, a team at the J. Craig Venter Institute published an article in Science Express, saying that they had successfully transplanted the natural DNA from a Mycoplasma mycoides bacterium into a Mycoplasma capricolum cell, creating a bacterium which behaved like a M. mycoides.

On Oct 6, 2007, Craig Venter announced in an interview with UK's The Guardian newspaper that the same team had synthesized a modified version of the single chromosome of Mycoplasma genitalium using chemicals. The chromosome was modified to eliminate all genes which tests in live bacteria had shown to be unnecessary. The next planned step in this minimal genome project is to transplant the synthesized minimal genome into a bacterial cell with its old DNA removed; the resulting bacterium will be called Mycoplasma laboratorium. The next day the Canadian bioethics group, ETC Group issued a statement through their representative, Pat Mooney, saying Venter's "creation" was "a chassis on which you could build almost anything". The synthesized genome had not yet been transplanted into a working cell.

On May 21, 2010, Science reported that the Venter group had successfully synthesized the genome of the bacterium Mycoplasma mycoides from a computer record, and transplanted the synthesized genome into the existing cell of a Mycoplasma capricolum bacterium that had had its DNA removed. The "synthetic" bacterium was viable, i.e. capable of replicating billions of times. The team had originally planned to use the M. genitalium bacterium they had previously been working with, but switched to M. mycoides because the latter bacterium grows much faster, which translated into quicker experiments. They have also shown that the natural genome of M. mycoides can be transplanted but has yet to show that the same could be done for M. genitalium. Venter describes it as "the first species.... to have its parents be a computer". The transformed bacterium is dubbed "Synthia" by ETC. A Venter spokesperson has declined to confirm any breakthrough at the time of this writing, likely because similar genetic introduction techniques such as transfection, transformation, transduction and protofection have been a standard research practice for many years.

Now that the technique has been proven to work with the M. mycoides genome, the next project is presumably to go back to the minimized M. genitalium and transplant it into a cell to create the previously mentioned Mycoplasma laboratorium.