Essential Science: Semi-synthetic bacterium created

Posted Mar 27, 2016 by Tim Sandle
Scientists have created a semi-synthetic, functioning bacterium in the lab that has fewer than 500 genes. The importance of "500" is that no bacterium in nature has less than 500 genes.
JCVI-syn3.0 (Image: Tom Deerinck and Mark Ellisman of the National Center for Imaging and Microscopy...
JCVI-syn3.0 (Image: Tom Deerinck and Mark Ellisman of the National Center for Imaging and Microscopy Research at the University of California at San Diego)
Tom Deerinck and Mark Ellisman
The organism "created" is Mycoplasma mycoides. The origins of the experiment date back to 2010, when a 1079-kb genome based organism was created. With the new experiment, a 531 kb (473 gene) version has been developed. "kb" refers to the genome size (the genome is the genetic material of an organism.) The essential unit is the "bp" or "base pair," the basic building block of DNA (for example, guanine-cytosine and adenine-thymine.)
In relation to the type organism in question, Mycoplasma are relatively less complex genus of bacteria that lack a cell wall around their cell membrane. The lack of a cell wall confers a resistance, to those strains that are pathogenic, to many types of antimicrobial compounds (including penicillin or other beta-lactam antibiotics.) With the specific species studied, M. mycoides is a parasite that lives in ruminants.
The 2010 study formed part of the part of the Minimal Genome Project. The project undertook the first complete cellular genome sequences of Mycoplasma organisms in 1995. This was of Haemophilus influenzae, a bacterium that causes many common childhood infections.
The 2010 experiment involved researchers synthesizing a modified version of M. mycoides (coded JCVI-syn1.0) and implanted it into a DNA-free bacterial shell of Mycoplasma capricolum. This other Mycoplasma species that had been emptied of its genome, and then "booted up" through the addition of JCVI-syn1.0.
The modified organism was capable of replication and therefore considered viable. To protect the "intellectual property," the researchers added a genetic watermark to the bacterium. The watermarks were coded messages in the form of DNA base pairs, of 1246, 1081, 1109 and 1222 base pairs respectively. The watermarks were not approved of by all in the scientific community, and were regarded by some geneticists as a publicity stunt.
The 2016 study, used genes from the JCVI-syn1.0 version to synthesize an even smaller genome. This has been coded JCVI-syn3.0. This is the organism with the 473 genes (531,560 base pairs.) With this, Syn 3.0 can operate with around 50 fewer genes that Syn1.0. The success indicates that organisms contain many genes needed for essential functions, but only a key number are required for actual life.
Discussing the research, lead scientist Dr. Daniel Gibson told the BBC: "Our long-term vision has been to design and build synthetic organisms on demand where you can add in specific functions and predict what the outcome is going to be."
Thus the aim of the research was two-fold. The first was to further understand the genetic basis of life. The second had a commercial aspect, and was designed to see if such research can provided the basis for manufacturing new drugs and chemicals. Microbial life is the basis of many pharmaceutical and chemical applications. This is the basis of "biotechnology", as the United Nations defines the science: "any technological application that uses biological systems, living organisms or derivatives thereof, to make or modify products or processes for specific use." The most likely future applications of the research rest with biofuel production or bioremediation (to clear up bio-waste, like oil spills.)
The research group behind the semi-synthetic bacterium project was backed by U.S. research entrepreneur Craig Venter. Venter is a biotechnologist, biochemist, geneticist by training. The founder of Celera Genomics, he was one of the first people to sequence the human genome.
An important point to make, and to avoid the 'wilder claims' made in some other media that have reported on this news, the modified bacterium is not a truly synthetic life form because its genome was put into an existing cell. One day the research institute aims to synthesize an organism consisting of only 256 genes, which is considered to be a minimal set of genes needed for viability. It should be noted that there is a difference between genes needed for "viability" an those required for "robust growth", simply creating a living organism doesn't mean the organism will grow particularly well. Moreover, it may only grow on a specially designed laboratory medium (with optimal nutrients) rather than in the natural environment.
To achieve this will require further painstaking studies: selectively removing each gene until the final number (and sequence) for minimal life is found. After this, it should be theoretically possible to design a genetic blueprint for a simple human-made bacterium. There is a way to go, however; of Syn 3.0's 473 necessary genes, the research indicates that 149 remain a scientific mystery in terms of their function. In relation to this, Jack Szostak, a biochemist at Harvard University who was not involved in the study, told Quantum Magazine, “To me, the most interesting thing is what it tells us about what we don’t know. So many genes of unknown function seem to be essential."
Such a move, where amino acids, fats and sugars could effectively be thrown together to create life, carries social and ethical considerations. Such a process could be used for good; however, it could also carry considerable risks, such as applications in biological warfare. To add fuel to the debate, Craig Venter told Forbes this was "the first designer organism in history."
The research is published in the journal Science, in a paper titled "Design and synthesis of a minimal bacterial genome."
This article is one of Digital Journal's Essential Science columns. Each week we explore a topical and important scientific issue. Last week we examined a theory that Jupiter had once bumped other proto-planets out of the way in its journey away from the Sun, billions of years ago. The previous week, a possible connection between viral and bacterial pathogens and the neurodegenerative disorder Alzheimer's disease was discussed.