World's simplest synthetic cell reveals gaps in genetic knowledge

Scientists have designed and created a functional, self-replicating cell containing only 473 genes – the smallest genome of any organism to be grown in a lab.

The cell, which contains 531,560 base-pairs and is known as JCVI Syn3.0, was developed by a team of scientists led by Dr Craig Venter, who was also behind the creation of the first man-made cell in 2010 (see BioNews 599). That cell, a copy of the simple bacterium Mycoplasma mycoides, contained 1.08 million base pairs and 901 genes.

The scientists have said that the purpose of reducing a cell to its most essential components was not only to gain a better grasp of essential biology but also to establish a 'chassis for use in industrial applications'.

The researchers began by designing hypothetical minimal genomes in eight different segments, each of which could be tested to see whether the constituent genes were essential or not. During this process the researchers identified what they called 'quasi-essential genes' which while not absolutely required for life, would be necessary if the cell was not to replicate so slowly that it would be almost useless in any future application.

In the final analysis, 149 of the organism's genes could not be assigned a specific biological function despite intensive study.

Speaking to The Guardian, Dr Venter said: 'We know about two thirds of essential biology. We are missing a third, which is a very important lesson.'

He added that only understanding two thirds of the most fundamental cell that could be built led him to believe that 'we are probably at about the one percent level of our understanding of the human genome'. The human genome is thought to contain between 20,000 to 25,000 protein-coding genes.

During the design-build-test process the researchers discovered that multiple genes often covered essential or quasi-essential functions. In this way, a gene that would initially be tagged as non-essential would actually turn out to be essential, but that would only be revealed if its partner were also removed.

Dr Venter likened this to reverse engineering a jet aeroplane which would still fly should one engine be removed. 'You don’t really discover the essentiality [of a jet engine] until you remove the second one,' he said.

The study of JCVI Syn3.0 was published in the journal Science.