Geneticists have designed and synthesized a minimal bacterial genome containing only the genes absolutely necessary for life.
With just 473 genes, this new organism, scientifically known as JCVI-Syn3.0, is the smallest and most simple genome of any living, self-replicating cell found in nature. For comparison, humans and fruit flies have more than 20,000 genes each. This, researchers say, may provide important insights into the fundamental genetic requirements for life.
This genome was engineered by synthetic biologist J. Craig Venter and microbiologist Clyde Hutchison. What's even more remarkable is about one-third of the bacterium's genes relate to unknown, but critical biological functions.
"Our attempt to design and create a new species, while ultimately successful, revealed that 32 percent of the genes essential for life in this cell are of unknown function, and showed that many are highly conserved in numerous species," explained Venter, founder of the J. Craig Venter Institute (JCVI). "All the bioinformatics studies over the past 20 years have underestimated the number of essential genes by focusing only on the known world. This is an important observation that we are carrying forward into the study of the human genome."
In 2010, Venter's team fashioned the first synthetic bacterium, Mycoplasma mycoides. This, however, was only a control experiment. What researchers were truly interested in was creating a cell with a minimal genome.
So the next step was to whittle the bacterium - Syn1.0 - down to its bare essentials. To start, the researchers divided the bacterium's genome - comprised of 901 genes - into eight different segments that could be individually altered and tested. By removing a segment, deleting chunks of DNA, and then reassembling the full genome and reinserting it into the bacterium M. capricolum, researchers were able to see whether it produced a living cell. If the altered genome wasn't viable, they knew they had cut out an essential gene that had to be restored.
Researchers also assessed the necessity of numerous genes by inserting foreign genetic material, known as transposons, to disrupt their function. After hundreds of constructs, the team finally settled on Syn3.0, whose genome is about half the size of Syn1.0's.
While the end result of their research has numerous real-world applications, Venter said the primary goal from day one has been biological knowledge.
"This paper signifies a major step toward our ability to design and build synthetic organisms from the bottom up with predictable outcomes," added Daniel G. Gibson, JCVI researcher. "The tools and knowledge gained from this work will be essential to producing next generation production platforms for a wide range of disciplines."
Their study was recently published in the journal Science.
